AchondroPlasiaEscape Game
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Test and apply your knowledge about achondroplasia!
The mission
You and your team are elite medical researchers at the forefront of conditions associated with genetic medicine. Simon, age 5, with achondroplasia is relying on your expertise to develop an endocrine therapy for his genetic variant to improve his quality of life. The lab’s AI system, GENIX has locked critical research data behind a series of puzzles to ensure only the most skilled researchers can access it. Your mission – should you choose to accept it – is to unlock the research data and formulate a treatment, within 3 attempts for each puzzle. How quickly you can beat other researchers in helping Simon?
Background image: Genially Hospital Lockdown example. https://view.genially.com/68f00a9fb32f660959285859/interactive-content-medical.
ASCEND Medical Center
You stroll into work, wondering what's in store for you today.
Image generated by ChatGPT.
Your Research Lab
Find the clue you need to keep moving forward
Background and book image generated from ChatGPT. Growth plate image from: Abad V, et al. Endocrinology. 2022;143:1851-7. FGF and CNP images from PubChem. FGFR3 image from Wikipedia.
Your Research Lab
Locked
Locked
Mission 1
Locked
Locked
Code used for timer is stored on last (hidden) page
Bone Tissue and Skeletal System. In Betts JG, et al. Anatomy & Physiology. OpenStax; 2013. Available at: https://openstax.org/books/anatomy-and-physiology/pages/6-introduction. Accessed October 1, 2025. Khalid K, et al. Br J Radiol. 2021;94:20210223. Image adapted from Servier Medical Art under Creative Commons Attribution 3.0 unported license.
Mission Failed
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TO LECTURE HALL
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Bone Tissue and Skeletal System. In Betts JG, et al. Anatomy & Physiology. OpenStax; 2013. Available at: https://openstax.org/books/anatomy-and-physiology/pages/6-introduction. Accessed October 1, 2025. Khalid K, et al. Br J Radiol. 2021;94:20210223. Image adapted from Servier Medical Art under Creative Commons Attribution 3.0 unported license.
Background image generated by ChatGPT.
You have 2 attempts left
Bone Tissue and Skeletal System. In Betts JG, et al. Anatomy & Physiology. OpenStax; 2013. Available at: https://openstax.org/books/anatomy-and-physiology/pages/6-introduction. Accessed October 1, 2025. Khalid K, et al. Br J Radiol. 2021;94:20210223. Image adapted from Servier Medical Art under Creative Commons Attribution 3.0 unported license.
Mission Failed
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TO LECTURE HALL
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Bone Tissue and Skeletal System. In Betts JG, et al. Anatomy & Physiology. OpenStax; 2013. Available at: https://openstax.org/books/anatomy-and-physiology/pages/6-introduction. Accessed October 1, 2025. Khalid K, et al. Br J Radiol. 2021;94:20210223. Image adapted from Servier Medical Art under Creative Commons Attribution 3.0 unported license.
Background image generated by ChatGPT.
This is your final attempt
Mission failed, moving on...
Bone Tissue and Skeletal System. In Betts JG, et al. Anatomy & Physiology. OpenStax; 2013. Available at: https://openstax.org/books/anatomy-and-physiology/pages/6-introduction. Accessed October 1, 2025. Khalid K, et al. Br J Radiol. 2021;94:20210223. Image adapted from Servier Medical Art under Creative Commons Attribution 3.0 unported license.
Image adapted from Pacifici M, et al. Musculoskeletal Key. Published April 14, 2020. https://musculoskeletalkey.com/the-development-growth-and-morphogenesis-of-the-skeleton/. Accessed February 18, 2026.Khalid K, et al. Br J Radiol. 2021;4:20210223.
Mission Failed
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TO LECTURE HALL
Facial bones formed by intramembranous ossification (white) are typically less affected in achrondroplasia.
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Image adapted from Pacifici M, et al. Musculoskeletal Key. Published April 14, 2020. https://musculoskeletalkey.com/the-development-growth-and-morphogenesis-of-the-skeleton/. Accessed February 18, 2026.Khalid K, et al. Br J Radiol. 2021;4:20210223.
You have 2 attempts left
Image adapted from Pacifici M, et al. Musculoskeletal Key. Published April 14, 2020. https://musculoskeletalkey.com/the-development-growth-and-morphogenesis-of-the-skeleton/. Accessed February 18, 2026.Khalid K, et al. Br J Radiol. 2021;4:20210223.
Mission Failed
You are still locked in...
TO LECTURE HALL
Facial bones formed from intramembranous ossification (white) are typically less impacted in achrondroplasia.
Try Again
Image adapted from Pacifici M, et al. Musculoskeletal Key. Published April 14, 2020. https://musculoskeletalkey.com/the-development-growth-and-morphogenesis-of-the-skeleton/. Accessed February 18, 2026.Khalid K, et al. Br J Radiol. 2021;4:20210223.
This is your final attempt
Mission failed, moving on...
Image adapted from Pacifici M, et al. Musculoskeletal Key. Published April 14, 2020. https://musculoskeletalkey.com/the-development-growth-and-morphogenesis-of-the-skeleton/. Accessed February 18, 2026.Khalid K, et al. Br J Radiol. 2021;4:20210223.
Your Research Lab
Completed
Mission 2
Locked
Locked
Locked
Agirdil Y. EFORT Open Rev. 2020;5:498-507.
Image from Agirdil 2020.
Mission Failed
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TO LECTURE HALL
Chondrocytes progress from a resting state to enter the phases of proliferation and hypertrophy. Under the influence of oestrogen, the proliferation of chondrocytes decreases as the resting chondrocytes are consumed. During the terminal phase of differentiation, cartilage is replaced by blood vessels and organized bone tissue, and once chondrocytes have died, the longitudinal growth of the bone ceases and the growth plate closes.
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Agirdil Y. EFORT Open Rev. 2020;5:498-507.
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You have 2 attempts left
Agirdil Y. EFORT Open Rev. 2020;5:498-507.
Image from Agirdil 2020.
Mission Failed
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TO LECTURE HALL
Chondrocytes progress from a resting state to enter the phases of proliferation and hypertrophy. Under the influence of oestrogen, the proliferation of chondrocytes decreases as the resting chondrocytes are consumed. During the terminal phase of differentiation, cartilage is replaced by blood vessels and organized bone tissue, and once chondrocytes have died, the longitudinal growth of the bone ceases and the growth plate closes.
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Agirdil Y. EFORT Open Rev. 2020;5:498-507.
Image generated by ChatGPT. Audio from Pixabay.
This is your final attempt
Mission failed, moving on...
Agirdil Y. EFORT Open Rev. 2020;5:498-507.
Image from Agirdil 2020.
FGFR3
Agirdil Y. EFORT Open Rev. 2020;5:498-507.
Image from Agirdil 2020 and https://en.wikipedia.org/wiki/Fibroblast_growth_factor_receptor_3.
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TO LECTURE HALL
FGFs play a critical role in regulating chondrocyte proliferation, differentiation, and hypertrophy in the growth plate. FGFs inhibit chondrocyte proliferation, thereby limiting longitudinal bone growth. Specifically, FGF is involved in chondrocyte maturation. FGFs also interact antagonistically with BMP and Ihh signaling, which promotes chondrocyte differentiation. Overexpression of FGFR3 is linked to achondroplasia.
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Agirdil Y. EFORT Open Rev. 2020;5:498-507.
Image generated by ChatGPT.
You have 2 attempts left
FGFR3
Agirdil Y. EFORT Open Rev. 2020;5:498-507.
Image from Agirdil 2020 and https://en.wikipedia.org/wiki/Fibroblast_growth_factor_receptor_3.
Mission Failed
You are still locked in...
TO LECTURE HALL
FGFs play a critical role in regulating chondrocyte proliferation, differentiation, and hypertrophy in the growth plate. FGFs inhibit chondrocyte proliferation, thereby limiting longitudinal bone growth. Specifically, FGF is involved in chondrocyte maturation. FGFs also interact antagonistically with BMP and Ihh signaling, which promotes chondrocyte differentiation. Overexpression of FGFR3 is linked to achondroplasia.
Try Again
Agirdil Y. EFORT Open Rev. 2020;5:498-507.
Image generated by ChatGPT.
This is your final attempt
Mission failed, moving on...
FGFR3
Agirdil Y. EFORT Open Rev. 2020;5:498-507.
Image from Agirdil 2020 and https://en.wikipedia.org/wiki/Fibroblast_growth_factor_receptor_3.
Your Research Lab
Completed
Mission 3
Completed
Locked
Locked
Glycine Arginine Lysine
CNP, C-type natriuretic peptide; FGFR3, fibroblast growth factor receptor 3.Rousseau F, et al. Horm Res. 1996;45:108-110. Images adapted from National Institute of Health. https://pubchem.ncbi.nlm.nih.gov/.
Mission Failed
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TO LECTURE HALL
Achondroplasia is primarily caused by a specific genetic variant in the FGFR3 (Fibroblast Growth Factor Receptor 3) gene located on chromosome 4, which leads to an amino acid substitution. The most common genetic variant is a glycine to arginine substitution at position 380 of the FGFR3 protein, denoted as G380R. This mutation is a result of a G to A transition in the nucleotide sequence.
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Rousseau F, et al. Horm Res. 1996;45:108-110.
Image generated by ChatGPT. Audio from Pixabay.
You have 2 attempts left
Glycine Arginine Lysine
CNP, C-type natriuretic peptide; FGFR3, fibroblast growth factor receptor 3.Rousseau F, et al. Horm Res. 1996;45:108-110. Images adapted from National Institute of Health. https://pubchem.ncbi.nlm.nih.gov/.
Mission Failed
You are still locked in...
TO LECTURE HALL
Achondroplasia is primarily caused by a specific genetic variant in the FGFR3 (Fibroblast Growth Factor Receptor 3) gene located on chromosome 4, which leads to an amino acid substitution. The most common genetic variant is a glycine to arginine substitution at position 380 of the FGFR3 protein, denoted as G380R. This mutation is a result of a G to A transition in the nucleotide sequence.
Try Again
Rousseau F, et al. Horm Res. 1996;45:108-110.
Image generated by ChatGPT. Audio from Pixabay.
This is your final attempt
Mission failed, moving on...
Glycine Arginine Lysine
CNP, C-type natriuretic peptide; FGFR3, fibroblast growth factor receptor 3.Rousseau F, et al. Horm Res. 1996;45:108-110. Images adapted from National Institute of Health. https://pubchem.ncbi.nlm.nih.gov/.
Your Research Lab
Completed
Completed
Completed
Locked
Mission 4
CNP, C-type natriuretic peptide; FGFR3, fibroblast growth factor receptor 3. 1. Legare JM, et al. Front Pediatr. 2023;11:1229666. 2. Jurcă MC, et al. Rom J Morphol Embryol. 2021; 62:689-696. 3. Horton WA, et al. Lancet. 2007;370:162-172. 4. Rintz E, et al. Int J Mol Sci. 2022;23:5916. 5. Krejci P, et al. PLoS One. 2008;3:e3961. 6. Yasoda A, et al. Nat Med. 2004;10: 80-86. 7. Miyazawa T, et al. Endocrinology. 2002;143:3604-3610. 8. Savarirayan R, et al. Nat Rev Endocrinol. 2022;18:173-189. 9. Wrobel W, et al. Int J Mol Sci. 2021;22:5573. 10 Laederich MB, et al. Curr Opin Pediatr. 2010;22:516-523.
Mission Failed
You are still locked in...
TO LECTURE HALL
Try Again
CNP, C-type natriuretic peptide; FGFR3, fibroblast growth factor receptor 3. 1. Legare JM, et al. Front Pediatr. 2023;11:1229666. 2. Jurcă MC, et al. Rom J Morphol Embryol. 2021; 62:689-696. 3. Horton WA, et al. Lancet. 2007;370:162-172. 4. Rintz E, et al. Int J Mol Sci. 2022;23:5916. 5. Krejci P, et al. PLoS One. 2008;3:e3961. 6. Yasoda A, et al. Nat Med. 2004;10: 80-86. 7. Miyazawa T, et al. Endocrinology. 2002;143:3604-3610. 8. Savarirayan R, et al. Nat Rev Endocrinol. 2022;18:173-189. 9. Wrobel W, et al. Int J Mol Sci. 2021;22:5573. 10 Laederich MB, et al. Curr Opin Pediatr. 2010;22:516-523.
Image adapted from ChatGPT.
You have 2 attempts left
CNP, C-type natriuretic peptide; FGFR3, fibroblast growth factor receptor 3. 1. Legare JM, et al. Front Pediatr. 2023;11:1229666. 2. Jurcă MC, et al. Rom J Morphol Embryol. 2021; 62:689-696. 3. Horton WA, et al. Lancet. 2007;370:162-172. 4. Rintz E, et al. Int J Mol Sci. 2022;23:5916. 5. Krejci P, et al. PLoS One. 2008;3:e3961. 6. Yasoda A, et al. Nat Med. 2004;10: 80-86. 7. Miyazawa T, et al. Endocrinology. 2002;143:3604-3610. 8. Savarirayan R, et al. Nat Rev Endocrinol. 2022;18:173-189. 9. Wrobel W, et al. Int J Mol Sci. 2021;22:5573. 10 Laederich MB, et al. Curr Opin Pediatr. 2010;22:516-523.
Mission Failed
You are still locked in...
TO LECTURE HALL
Try Again
CNP, C-type natriuretic peptide; FGFR3, fibroblast growth factor receptor 3. 1. Legare JM, et al. Front Pediatr. 2023;11:1229666. 2. Jurcă MC, et al. Rom J Morphol Embryol. 2021; 62:689-696. 3. Horton WA, et al. Lancet. 2007;370:162-172. 4. Rintz E, et al. Int J Mol Sci. 2022;23:5916. 5. Krejci P, et al. PLoS One. 2008;3:e3961. 6. Yasoda A, et al. Nat Med. 2004;10: 80-86. 7. Miyazawa T, et al. Endocrinology. 2002;143:3604-3610. 8. Savarirayan R, et al. Nat Rev Endocrinol. 2022;18:173-189. 9. Wrobel W, et al. Int J Mol Sci. 2021;22:5573. 10 Laederich MB, et al. Curr Opin Pediatr. 2010;22:516-523.
Image adapted from ChatGPT.
This is your final attempt
Mission failed, moving on...
CNP, C-type natriuretic peptide; FGFR3, fibroblast growth factor receptor 3. 1. Legare JM, et al. Front Pediatr. 2023;11:1229666. 2. Jurcă MC, et al. Rom J Morphol Embryol. 2021; 62:689-696. 3. Horton WA, et al. Lancet. 2007;370:162-172. 4. Rintz E, et al. Int J Mol Sci. 2022;23:5916. 5. Krejci P, et al. PLoS One. 2008;3:e3961. 6. Yasoda A, et al. Nat Med. 2004;10: 80-86. 7. Miyazawa T, et al. Endocrinology. 2002;143:3604-3610. 8. Savarirayan R, et al. Nat Rev Endocrinol. 2022;18:173-189. 9. Wrobel W, et al. Int J Mol Sci. 2021;22:5573. 10 Laederich MB, et al. Curr Opin Pediatr. 2010;22:516-523.
Completada
Completada
Completada
Completada
Your Research Lab
Completed
Completed
Completed
Completed
Mission 5
Savarirayan R., et al. Nat Rev Endocrinol. 2022;18:173-189.
Mission Failed
You are still locked in...
TO LECTURE HALL
Achondroplasia is one of a small number of so-called RAMP disorders – Recurrent, Autosomal-dominant, Male-biased, Paternal age effect disorders – all of which likely arise because of their positive selective effect on spermatogonia. However, 80% of patients are born to parents of normal height. Mom and Dad do not have achondroplasia, although they are shorter than the general population. Hypochondroplasia and achondroplasia arise from a systemic fibroblast growth factor receptor 3 (FGFR3) variant, but they are distinct conditions.
Try Again
Savarirayan R., et al. Nat Rev Endocrinol. 2022;18:173-189.
Image adapted from ChatGPT.
You have 2 attempts left
Savarirayan R., et al. Nat Rev Endocrinol. 2022;18:173-189.
Mission Failed
You are still locked in...
TO LECTURE HALL
Achondroplasia is one of a small number of so-called RAMP disorders – Recurrent, Autosomal-dominant, Male-biased, Paternal age effect disorders – all of which likely arise because of their positive selective effect on spermatogonia. However, 80% of patients are born to parents of normal height. Mom and Dad do not have achondroplasia, although they are shorter than the general population. Hypochondroplasia and achondroplasia arise from a systemic fibroblast growth factor receptor 3 (FGFR3) variant, but they are distinct conditions.
Try Again
Savarirayan R., et al. Nat Rev Endocrinol. 2022;18:173-189.
Image adapted from ChatGPT.
This is your final attempt
Mission failed, moving on...
Savarirayan R., et al. Nat Rev Endocrinol. 2022;18:173-189.
Completed
Completed
Completed
Completed
Completed
Your Research Lab
Completed
Completed
Completed
Completed
Completed
Continue
Your Research Lab
Interestingly, GENIX generates a dial tone. Right away, you hear a ring from a phone booth just OUTSIDE your office! You drop everything and go check it out...
GENIX DATA UNLOCKED
You pick up the phone. "Hello? Hello?"A voice responds – "Remember the code..."
380
Continue
ASCEND Medical Center
You completed the puzzles in the Research Lab. Where's next?
Image generated by ChatGPT.
The Advanced Clinical Lab requires a numerical code to enter.
You recall that your colleague recently changed the code, and has left you a note in a locked mailbox.
Where's the Key?
Only authorized clinicians can enter the Advanced Clinical Lab. Find and grab the Key to continue.
Lab2026
I better remember this code...
Head to Clinical Lab
The Advanced Clinical Lab requires a numerical code to enter.
Enter the updated 4-digit code.
You have 2 attempts left
The Advanced Clinical Lab requires a numerical code to enter.
Enter the updated 4‑digit code (the year the U.S. Food and Drug Administration approved Yuviwel (navepegritide) for achondroplasia in pediatric patients aged two years and older with with open growth plates)
Refer to the following and try again – Note from your colleague left in the locked mailbox.
This is your final attempt
Mission failed, moving on...
The Advanced Clinical Lab requires a numerical code to enter.
Enter the updated 4‑digit code (the year the U.S. Food and Drug Administration approved Yuviwel (navepegritide) for achondroplasia in pediatric patients aged two years and older with with open growth plates)
Refer to the following and try again – Note from your colleague left in the locked mailbox.
Advanced Clinical Lab
Explore to keep moving forward
Advanced Clinical Lab
Locked
Locked
Mission 1
Locked
Locked
Locked
Match each clinical manifestation to its corresponding complication to reveal the correct code.
Complication
Foramen magnum stenosis
Hydrocephalus
Thoracolumbar kyphosis
Genu varum
Spinal (lumbar) stenosis
Sleep apnea / ear infections
Mindler GT, et al. J Child Orthop. 2024;18:461-476. Image adapted from Servier Medical Art under Creative Commons Attribution 3.0 unported license.
Mission Failed
You are still locked in...
To Lecture Hall
Refer to the following (click on image):
Try Again
Mindler GT, et al. J Child Orthop. 2024;18:461-476.
Image adapted from ChatGPT.
You have 2 attempts left
Match each clinical manifestation to its corresponding complication to reveal the correct code.
Complication
Foramen magnum stenosis
Hydrocephalus
Thoracolumbar kyphosis
Genu varum
Spinal (lumbar) stenosis
Sleep apnea / ear infections
Mindler GT, et al. J Child Orthop. 2024;18:461-476. Image adapted from Servier Medical Art under Creative Commons Attribution 3.0 unported license.
Mission Failed
You are still locked in...
To Lecture Hall
Refer to the following (click on image):
Try Again
Mindler GT, et al. J Child Orthop. 2024;18:461-476.
Image adapted from ChatGPT.
This is your final attempt
Mission failed, moving on...
Match each clinical manifestation to its corresponding complication to reveal the correct code.
Complication
Foramen magnum stenosis
Hydrocephalus
Thoracolumbar kyphosis
Genu varum
Spinal (lumbar) stenosis
Sleep apnea / ear infections
Mindler GT, et al. J Child Orthop. 2024;18:461-476. Image adapted from Servier Medical Art under Creative Commons Attribution 3.0 unported license.
Match each management option to its corresponding complication to reveal the correct code.
Complication
Clinical Manifestation
[L] Weakness, apnea, feeding issues, irritability
Foramen magnum stenosis
[D] Rapid head growth, headache, vomiting
Hydrocephalus
[R] Spinal curve ("hump") in infants
Thoracolumbar kyphosis
[I] Gait issues, pain, arthritic risk
Genu varum
[G] Leg pain, numbness, claudication, urinary issues
Spinal (lumbar) stenosis
[S] Snoring, apnea, hearing loss
Sleep apnea / ear infections
CPAP, continuous positive airway pressure; MRI, magnetic resonace imaging; VP, ventriculoperitoneal.Mindler GT, et al. J Child Orthop. 2024;18:461-476. Image adapted from Servier Medical Art under Creative Commons Attribution 3.0 unported license.
Mission Failed
You are still locked in...
To Lecture Hall
Refer to the following (click on image):
Try Again
Mindler GT, et al. J Child Orthop. 2024;18:461-476.
Image adapted from ChatGPT.
You have 2 attempts left
Match each management option to its corresponding complication to reveal the correct code.
Complication
Clinical Manifestation
[L] Weakness, apnea, feeding issues, irritability
Foramen magnum stenosis
[D] Rapid head growth, headache, vomiting
Hydrocephalus
[R] Spinal curve ("hump") in infants
Thoracolumbar kyphosis
[I] Gait issues, pain, arthritic risk
Genu varum
[G] Leg pain, numbness, claudication, urinary issues
Spinal (lumbar) stenosis
[S] Snoring, apnea, hearing loss
Sleep apnea / ear infections
CPAP, continuous positive airway pressure; MRI, magnetic resonace imaging; VP, ventriculoperitoneal.Mindler GT, et al. J Child Orthop. 2024;18:461-476. Image adapted from Servier Medical Art under Creative Commons Attribution 3.0 unported license.
Mission Failed
You are still locked in...
To Lecture Hall
Refer to the following (click on image):
Try Again
Mindler GT, et al. J Child Orthop. 2024;18:461-476.
Image adapted from ChatGPT.
This is your final attempt
Mission failed, moving on...
Match each management option to its corresponding complication to reveal the correct code.
Complication
Clinical Manifestation
[L] Weakness, apnea, feeding issues, irritability
Foramen magnum stenosis
[D] Rapid head growth, headache, vomiting
Hydrocephalus
[R] Spinal curve ("hump") in infants
Thoracolumbar kyphosis
[I] Gait issues, pain, arthritic risk
Genu varum
[G] Leg pain, numbness, claudication, urinary issues
Spinal (lumbar) stenosis
[S] Snoring, apnea, hearing loss
Sleep apnea / ear infections
CPAP, continuous positive airway pressure; MRI, magnetic resonace imaging; VP, ventriculoperitoneal.Mindler GT, et al. J Child Orthop. 2024;18:461-476. Image adapted from Servier Medical Art under Creative Commons Attribution 3.0 unported license.
Match clinical manifestation and management options to each complication to reveal the correct code.
Complication
Management Options
[C] Adenotonsillectomy, CPAP, ear tubes, audiometry, speech therapy
[S] VP shunt; neuroimaging monitoring
[M] MRI → surgical decompression
[G] Restrict sitting, bracing, spinal fusion if severe
[G] Conservative first; decompression surgery if needed
[L] Guided growth, oesteotomy; limb-lengthening rarely
Clinical Manifestation
[S] Snoring, apnea, hearing loss
[D] Rapid head growth, headache, vomiting
[L] Weakness, apnea, feeding issues, irritability
[R] Spinal curve ("hump") in infants
[G] Leg pain, numbness, claudication, urinary issues
[I] Gait issues, pain, arthritic risk
Foramen magnum stenosis
Hydrocephalus
Thoracolumbar kyphosis
Genu varum
Spinal (lumbar) stenosis
Enter the 12-character code revealed from column B (first letter, top to bottom), then column C. This corresponds to the last 12 residues of endogenous human CNP-53.
Sleep apnea / ear infections
CPAP, continuous positive airway pressure; MRI, magnetic resonace imaging; VP, ventriculoperitoneal.Nakagawa Y, et al. Biology. 2022;11:986. Image adapted from Servier Medical Art under Creative Commons Attribution 3.0 unported license.
Mission Failed
You are still locked in...
TO LEcture Hall
Try Again
Nakagawa Y, et al. Biology. 2022;11:986.
Image adapted from ChatGPT.
You have 2 attempts left
Match clinical manifestation and management options to each complication to reveal the correct code.
Complication
Management Options
[C] Adenotonsillectomy, CPAP, ear tubes, audiometry, speech therapy
[S] VP shunt; neuroimaging monitoring
[M] MRI → surgical decompression
[G] Restrict sitting, bracing, spinal fusion if severe
[G] Conservative first; decompression surgery if needed
[L] Guided growth, oesteotomy; limb-lengthening rarely
Clinical Manifestation
[S] Snoring, apnea, hearing loss
[D] Rapid head growth, headache, vomiting
[L] Weakness, apnea, feeding issues, irritability
[R] Spinal curve ("hump") in infants
[G] Leg pain, numbness, claudication, urinary issues
[I] Gait issues, pain, arthritic risk
Foramen magnum stenosis
Hydrocephalus
Thoracolumbar kyphosis
Genu varum
Spinal (lumbar) stenosis
Enter the 12-character code revealed from column B (first letter, top to bottom), then column C. This corresponds to the last 12 residues of endogenous human CNP-53.
Sleep apnea / ear infections
CPAP, continuous positive airway pressure; MRI, magnetic resonace imaging; VP, ventriculoperitoneal.Nakagawa Y, et al. Biology. 2022;11:986. Image adapted from Servier Medical Art under Creative Commons Attribution 3.0 unported license.
Mission Failed
You are still locked in...
TO LEcture Hall
Try Again
Nakagawa Y, et al. Biology. 2022;11:986.
Image adapted from ChatGPT.
This is your final attempt
Mission failed, moving on...
Match clinical manifestation and management options to each complication to reveal the correct code.
Complication
Management Options
[C] Adenotonsillectomy, CPAP, ear tubes, audiometry, speech therapy
[S] VP shunt; neuroimaging monitoring
[M] MRI → surgical decompression
[G] Restrict sitting, bracing, spinal fusion if severe
[G] Conservative first; decompression surgery if needed
[L] Guided growth, oesteotomy; limb-lengthening rarely
Clinical Manifestation
[S] Snoring, apnea, hearing loss
[D] Rapid head growth, headache, vomiting
[L] Weakness, apnea, feeding issues, irritability
[R] Spinal curve ("hump") in infants
[G] Leg pain, numbness, claudication, urinary issues
[I] Gait issues, pain, arthritic risk
Foramen magnum stenosis
Hydrocephalus
Thoracolumbar kyphosis
Genu varum
Spinal (lumbar) stenosis
Enter the 12-character code revealed from column B (first letter, top to bottom), then column C. This corresponds to the last 12 residues of endogenous human CNP-53.
Sleep apnea / ear infections
CPAP, continuous positive airway pressure; MRI, magnetic resonace imaging; VP, ventriculoperitoneal.Nakagawa Y, et al. Biology. 2022;11:986. Image adapted from Servier Medical Art under Creative Commons Attribution 3.0 unported license.
LDRIGSMSGLGC
COntinue
Nakagawa Y, et al. Biology. 2022;11:986.
Image adapted from ChatGPT.
Advanced Clinical Lab
Completed
Mission 2
Locked
Locked
Locked
Locked
Case Study
A 5-year-old child with achondroplasia has the following lower limb measurements:
- Femoral mechanical axis angle: 12° valgus
- Tibial mechanical axis angle: 5° varus
- Tibia-Femoral Angle: 17° varus
- Distance from the center of the femoral head to the center of the ankle joint: 40 cm
- Distance from the center of the knee joint to the mechanical axis line: 3.5 cm medial to the center of the knee
- The following bone lengths are measured:
- Fibula length: 18.5 cm
- Tibia length: 17.0 cm
Explanation: MAD is the perpendicular distance from the mechanical axis line to the center of the knee. Since it's 3.5 cm medial, the deviation is 3.5 cm medial.
Continue
Marques L. et al. EFORT Open Rev. 2021;6:487-494.
Image from ChatGPT.
Mission Failed
You are still locked in...
To Lecture Hall
** Turn up for volume for audio description **
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Marques L. et al. EFORT Open Rev. 2021;6:487-494.
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Case Study
A 5-year-old child with achondroplasia has the following lower limb measurements:
- Femoral mechanical axis angle: 12° valgus
- Tibial mechanical axis angle: 5° varus
- Tibia-Femoral Angle: 17° varus
- Distance from the center of the femoral head to the center of the ankle joint: 40 cm
- Distance from the center of the knee joint to the mechanical axis line: 3.5 cm medial to the center of the knee
- The following bone lengths are measured:
- Fibula length: 18.5 cm
- Tibia length: 17.0 cm
Explanation: MAD is the perpendicular distance from the mechanical axis line to the center of the knee. Since it's 3.5 cm medial, the deviation is 3.5 cm medial.
Continue
Marques L. et al. EFORT Open Rev. 2021;6:487-494.
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Marques L. et al. EFORT Open Rev. 2021;6:487-494.
Image adapted from ChatGPT.
This is your final attempt
Mission failed, moving on...
Case Study
A 5-year-old child with achondroplasia has the following lower limb measurements:
- Femoral mechanical axis angle: 12° valgus
- Tibial mechanical axis angle: 5° varus
- Tibia-Femoral Angle: 17° varus
- Distance from the center of the femoral head to the center of the ankle joint: 40 cm
- Distance from the center of the knee joint to the mechanical axis line: 3.5 cm medial to the center of the knee
- The following bone lengths are measured:
- Fibula length: 18.5 cm
- Tibia length: 17.0 cm
Explanation: MAD is the perpendicular distance from the mechanical axis line to the center of the knee. Since it's 3.5 cm medial, the deviation is 3.5 cm medial.
Continue
Marques L. et al. EFORT Open Rev. 2021;6:487-494.
Image from ChatGPT.
Case Study
A 5-year-old child with achondroplasia has the following lower limb measurements:
- Femoral mechanical axis angle: 12° valgus
- Tibial mechanical axis angle: 5° varus
- Tibia-Femoral Angle: 17° varus
- Distance from the center of the femoral head to the center of the ankle joint: 40 cm
- Distance from the center of the knee joint to the mechanical axis line: 3.5 cm medial to the center of the knee
- The following bone lengths are measured:
- Fibula length: 18.5 cm
- Tibia length: 17.0 cm
Explanation: Fibula-to-tibia ratio = 18.5 cm / 17.0 cm ≈ 1.09
Continue
Ward LM, et al. ECE/ESPE 2025 ApproaCH Bone Morphometry Oral Presentation Slides (v2.0), slide 7.
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Ward LM, et al. ECE/ESPE 2025 ApproaCH Bone Morphometry Oral Presentation Slides (v2.0), slide 7.
Image adapted from ChatGPT.
You have 2 attempts left
Case Study
A 5-year-old child with achondroplasia has the following lower limb measurements:
- Femoral mechanical axis angle: 12° valgus
- Tibial mechanical axis angle: 5° varus
- Tibia-Femoral Angle: 17° varus
- Distance from the center of the femoral head to the center of the ankle joint: 40 cm
- Distance from the center of the knee joint to the mechanical axis line: 3.5 cm medial to the center of the knee
- The following bone lengths are measured:
- Fibula length: 18.5 cm
- Tibia length: 17.0 cm
Explanation: Fibula-to-tibia ratio = 18.5 cm / 17.0 cm ≈ 1.09
Continue
Ward LM, et al. ECE/ESPE 2025 ApproaCH Bone Morphometry Oral Presentation Slides (v2.0), slide 7.
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** Turn up for volume for audio description **
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Ward LM, et al. ECE/ESPE 2025 ApproaCH Bone Morphometry Oral Presentation Slides (v2.0), slide 7.
Image adapted from ChatGPT.
This is your final attempt
Mission failed, moving on...
Case Study
A 5-year-old child with achondroplasia has the following lower limb measurements:
- Femoral mechanical axis angle: 12° valgus
- Tibial mechanical axis angle: 5° varus
- Tibia-Femoral Angle: 17° varus
- Distance from the center of the femoral head to the center of the ankle joint: 40 cm
- Distance from the center of the knee joint to the mechanical axis line: 3.5 cm medial to the center of the knee
- The following bone lengths are measured:
- Fibula length: 18.5 cm
- Tibia length: 17.0 cm
Explanation: Fibula-to-tibia ratio = 18.5 cm / 17.0 cm ≈ 1.09
Continue
Ward LM, et al. ECE/ESPE 2025 ApproaCH Bone Morphometry Oral Presentation Slides (v2.0), slide 7.
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Advanced Clinical Lab
Completed
Mission 3
Completed
Locked
Locked
Locked
Case Study
A 6-year-old female named Emma, who is living with ACH, has a baseline height of 94.5 cm. Emma started Navepegritide therapy 12 months ago, and her height now is 100.8 cm. Calculate her AGV over the past year.
Continue
ACH, achondroplasia; AGV, annualized growth velocity.
1. Barstow C, et al. Am Fam Physician. 2015; 92.1: 43-50. 2. Bozzola, M, Meazza, C. (2012). Growth Velocity Curves: What They Are and How to Use Them. In: Preedy, V. (eds) Handbook of Growth and Growth Monitoring in Health and Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1795-9_180.
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1. Barstow C, et al. Am Fam Physician. 2015; 92.1: 43-50. 2. Bozzola, M, Meazza, C. (2012). Growth Velocity Curves: What They Are and How to Use Them. In: Preedy, V. (eds) Handbook of Growth and Growth Monitoring in Health and Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1795-9_180.
Image adapted from ChatGPT.
You have 2 attempts left
Case Study
A 6-year-old female named Emma, who is living with ACH, has a baseline height of 94.5 cm. Emma started Navepegritide therapy 12 months ago, and her height now is 100.8 cm. Calculate her AGV over the past year.
Continue
ACH, achondroplasia; AGV, annualized growth velocity.
1. Barstow C, et al. Am Fam Physician. 2015; 92.1: 43-50. 2. Bozzola, M, Meazza, C. (2012). Growth Velocity Curves: What They Are and How to Use Them. In: Preedy, V. (eds) Handbook of Growth and Growth Monitoring in Health and Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1795-9_180.
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1. Barstow C, et al. Am Fam Physician. 2015; 92.1: 43-50. 2. Bozzola, M, Meazza, C. (2012). Growth Velocity Curves: What They Are and How to Use Them. In: Preedy, V. (eds) Handbook of Growth and Growth Monitoring in Health and Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1795-9_180.
Image adapted from ChatGPT.
This is your final attempt
Mission failed, moving on...
Case Study
A 6-year-old female named Emma, who is living with ACH, has a baseline height of 94.5 cm. Emma started Navepegritide therapy 12 months ago, and her height now is 100.8 cm. Calculate her AGV over the past year.
Continue
ACH, achondroplasia; AGV, annualized growth velocity.
1. Barstow C, et al. Am Fam Physician. 2015; 92.1: 43-50. 2. Bozzola, M, Meazza, C. (2012). Growth Velocity Curves: What They Are and How to Use Them. In: Preedy, V. (eds) Handbook of Growth and Growth Monitoring in Health and Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1795-9_180.
1. Barstow C, et al. Am Fam Physician. 2015; 92.1: 43-50. 2. Bozzola, M, Meazza, C. (2012). Growth Velocity Curves: What They Are and How to Use Them. In: Preedy, V. (eds) Handbook of Growth and Growth Monitoring in Health and Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1795-9_180.
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Advanced Clinical Lab
Completed
Completed
Completed
Locked
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Mission 4
Case Study
Patient: Isabella, 6 years old Measured Height: 96.0 cm
Reference Data (CLARITY Achondroplasia Growth Chart):
- Mean height for age 6: 98.0 cm
- Standard deviation (SD): 2.5 cm
Continue
SDS, standard deviation score.Hoover-Fong JE, et al. Orphanet J Rare Dis. 2021;16:522.
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Hoover-Fong JE, et al. Orphanet J Rare Dis. 2021;16:522.
Image adapted from ChatGPT.
You have 2 attempts left
Case Study
Patient: Isabella, 6 years old Measured Height: 96.0 cm
Reference Data (CLARITY Achondroplasia Growth Chart):
- Mean height for age 6: 98.0 cm
- Standard deviation (SD): 2.5 cm
Continue
SDS, standard deviation score.Hoover-Fong JE, et al. Orphanet J Rare Dis. 2021;16:522.
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Hoover-Fong JE, et al. Orphanet J Rare Dis. 2021;16:522.
Image adapted from ChatGPT.
This is your final attempt
Mission failed, moving on...
Case Study
Patient: Isabella, 6 years old Measured Height: 96.0 cm
Reference Data (CLARITY Achondroplasia Growth Chart):
- Mean height for age 6: 98.0 cm
- Standard deviation (SD): 2.5 cm
Continue
SDS, standard deviation score.Hoover-Fong JE, et al. Orphanet J Rare Dis. 2021;16:522.
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Advanced Clinical Lab
Completed
Completed
Completed
Completed
Locked
Mission 5
Case Study
Patient: Noah, 6 years old at baseline Height: 95.0 cm Height SDS (CLARITY chart): –1.2
After 12 Months on Navepegritide Therapy:
- Height: 101.0 cm
- Height SDS (CLARITY chart): –0.7
Continue
SDS, standard deviation score.van Dommelen P, et al. Arch Dis Child. 2012;97.2:182.
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SDS, standard deviation score.van Dommelen P, et al. Arch Dis Child. 2012;97.2:182.
Image adapted from ChatGPT.
You have 2 attempts left
Case Study
Patient: Noah, 6 years old at baseline Height: 95.0 cm Height SDS (CLARITY chart): –1.2
After 12 Months on Navepegritide Therapy:
- Height: 101.0 cm
- Height SDS (CLARITY chart): –0.7
Continue
SDS, standard deviation score.van Dommelen P, et al. Arch Dis Child. 2012;97.2:182.
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SDS, standard deviation score.van Dommelen P, et al. Arch Dis Child. 2012;97.2:182.
Image adapted from ChatGPT.
This is your final attempt
Mission failed, moving on...
Case Study
Patient: Noah, 6 years old at baseline Height: 95.0 cm
Height SDS (CLARITY chart): –1.2
After 12 Months on Navepegritide Therapy:
- Height: 101.0 cm
- Height SDS (CLARITY chart): –0.7
Continue
SDS, standard deviation score.van Dommelen P, et al. Arch Dis Child. 2012;97.2:182.
Image from ChatGPT.
Advanced Clinical Lab
Completed
Completed
Completed
Completed
Completed
Mission 6
Step 1 – Drag each measured domain into the correct box for the ACEM-IMPACT tool or the ACEM-Observable Signs Measure (OSM).
Measured Domain
ACEM-IMPACT Tool
ACEM-OSM Tool
Physical Functioning
Pain
EmotionalWell-Being
BalanceIssues
Daily Living Functioning
EarProblems
School
SocialFunctioning
SocialWell-Being
Sleep Apnea
Low-stamina
Step 2 – Rearrange the yellow letters on each domain in ACEM-IMPACT to decode a word related to achondroplasia
Submit
ACEM, Achondroplasia Child Experience Measure.1. Pfeiffer KM, et al. Am J Med Genet A. 2021;185:33-45. 2. Data on file. Ascendis Pharma, 2025.
Image adapted from ChatGPT. Ascendis. Global_PES_2025_ Navepegretide_Improved_Physical_Functioning_training_deck
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1. Pfeiffer KM, et al. Am J Med Genet A. 2021;185:33-45. 2. Data on file. Ascendis Pharma, 2025.
Image adapted from ChatGPT. Ascendis. Global_PES_2025_ Navepegretide_Improved_Physical_Functioning_training_deck
You have 2 attempts left
Step 1 – Drag to sort each measured domain into the correct box for ACEM-IMPACT tool vs. ACEM-Observable Signs Measure (OSM).
Measured Domain
ACEM-IMPACT Tool
ACEM-OSM Tool
Physical Functioning
Daily Living Functioning
Pain
EmotionalWell-Being
BalanceIssues
EarProblems
SocialFunctioning
School
SocialWell-Being
Sleep Apnea
Low-stamina
Step 2 – Rearrange the yellow letters on each domain in ACEM-IMPACT to decode a word related to achondroplasia
Submit
ACEM, Achondroplasia Child Experience Measure.1. Pfeiffer KM, et al. Am J Med Genet A. 2021;185:33-45. 2. Data on file. Ascendis Pharma, 2025.
Image adapted from ChatGPT. Ascendis. Global_PES_2025_ Navepegretide_Improved_Physical_Functioning_training_deck
Mission Failed
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To Lecture Hall
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1. Pfeiffer KM, et al. Am J Med Genet A. 2021;185:33-45. 2. Data on file. Ascendis Pharma, 2025.
Image adapted from ChatGPT. Ascendis. Global_PES_2025_ Navepegretide_Improved_Physical_Functioning_training_deck
This is your final attempt
Mission failed, moving on...
Step 1 – Drag to sort each measured domain into the correct box for ACEM-IMPACT tool vs. ACEM-Observable Signs Measure (OSM).
Measured Domain
ACEM-IMPACT Tool
ACEM-OSM Tool
Physical Functioning
Daily Living Functioning
Pain
EmotionalWell-Being
BalanceIssues
EarProblems
SocialFunctioning
School
SocialWell-Being
Sleep Apnea
Low-stamina
Step 2 – Rearrange the yellow letters on each domain in ACEM-IMPACT to decode a word related to achondroplasia
Submit
ACEM, Achondroplasia Child Experience Measure.1. Pfeiffer KM, et al. Am J Med Genet A. 2021;185:33-45. 2. Data on file. Ascendis Pharma, 2025.
Image adapted from ChatGPT. Ascendis. Global_PES_2025_ Navepegretide_Improved_Physical_Functioning_training_deck
Advanced Clinical Lab
Completed
Completed
Completed
Completed
Completed
Completed
Continue
ASCEND Medical Center
You completed the puzzles in the Clinical Lab. Where's next?
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For the safety of our pediatric patients, the Patient Ward requires a numerical code to enter.
Enter the 3-digit code that corresponds to the highest dose of navepegritide (in mcg/kg/week) studied in our clinical trial program.
You have 2 attempts left
For the safety of our pediatric patients, the Patient Ward requires a numerical code to enter.
Enter the 3-digit code that corresponds to the highest dose of navepegritide (in mcg/kg/week) studied in our clinical trial program.
Refer to the following and try again – Breinholt VM, et al. Phase 1 safety, tolerability, pharmacokinetics and pharmacodynamics results of a long-acting C-type natriuretic peptide prodrug, TransCon CNP. Br J Clin Pharmacol. 2022;88:4763-4772.
This is your final attempt
Mission failed, moving on...
For the safety of our pediatric patients, the Patient Ward requires a numerical code to enter.
Enter the 3-digit code that corresponds to the highest dose of navepegritide (in mcg/kg/week) studied in our clinical trial program.
Refer to the following and try again – Breinholt VM, et al. Phase 1 safety, tolerability, pharmacokinetics and pharmacodynamics results of a long-acting C-type natriuretic peptide prodrug, TransCon CNP. Br J Clin Pharmacol. 2022;88:4763-4772.
Patient Ward
Mission 1
Locked
Locked
Locked
AGV, annualized growth velocity; LS, least-square.
Savarirayan R, et al. JAMA Pediatr. 2026;180:18-25.
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Savarirayan R, et al. JAMA Pediatr. 2026;180:18-25.
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You have 2 attempts left
Refer to the following and try again – Savarirayan R, et al. Once-weekly navepegritide in children with achondroplasia: the APPROACH randomized clinical trial. JAMA Pediatr. 2026;180:18-25.
AGV, annualized growth velocity; LS, least-square.
Savarirayan R, et al. JAMA Pediatr. 2026;180:18-25.
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Refer to the following (click on image):
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Savarirayan R, et al. JAMA Pediatr. 2026;180:18-25.
Image adapted from ChatGPT.
This is your final attempt
Mission failed, moving on...
Refer to the following and try again – Savarirayan R, et al. Once-weekly navepegritide in children with achondroplasia: the APPROACH randomized clinical trial. JAMA Pediatr. 2026;180:18-25.
AGV, annualized growth velocity; LS, least-square.
Savarirayan R, et al. JAMA Pediatr. 2026;180:18-25.
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Patient Ward
Mission 2
Locked
Completed
Locked
Savarirayan R, et al. EClinicalMedicine. 2023;65:102258.
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Mission Failed
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Refer to the following (click on image):
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Savarirayan R, et al. EClinicalMedicine. 2023;65:102258.
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Refer to the following and try again – Savarirayan R, et. al. Once-weekly TransCon CNP (navepegritide) in children with achondroplasia (AComplisH): a phase 2, multicentre, randomized, double-blind, placebo-controlled, dose escalation trial. EClinicalMedicine. 2023;65:102258.
Savarirayan R, et al. EClinicalMedicine. 2023;65:102258.
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Refer to the following (click on image):
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Savarirayan R, et al. EClinicalMedicine. 2023;65:102258.
Image adapted from ChatGPT.
This is your final attempt
Mission failed, moving on...
Refer to the following and try again – Savarirayan R, et. al. Once-weekly TransCon CNP (navepegritide) in children with achondroplasia (AComplisH): a phase 2, multicentre, randomized, double-blind, placebo-controlled, dose escalation trial. EClinicalMedicine. 2023;65:102258.
Savarirayan R, et al. EClinicalMedicine. 2023;65:102258.
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Patient Ward
Mission 3
Completed
Completed
Locked
1. Blum WF, et al. Endocr Connect. 2018;7:R212 R222. 2. Chikani V, et al. J Mol Endocrinol. 2013;52:R107-R123. 3. Sacca L, et al. Endocr Rev. 1994;15:555-573. 4. Isgaard J, et al. Endocrine. 2015;48:25-35. 5. Betts JG, et al. Anatomy and Physiology 2e. OpenStax Publications. 2022. Available at: https://openstax.org/details/books/anatomy-and-physiology-2e. 6. Olarescu NC, et al. Normal Physiology of Growth Hormone in Adults. In: Pituitary Disease and Neuroendocrinology. Levy M, Korbonits M, eds. Available at: https://www.endotext.org/sections/neuroendo/. 7. Yuen KCJ, et al. Endocr Pract. 2019;25:1191-1232. 8. Stabler B, et al. Horm Res. 1996;45(1-2):30-33. 9. Leong GM, et al. Horm Res. 2003;60(suppl 1):78-85.
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1. Blum WF, et al. Endocr Connect. 2018;7:R212 R222. 2. Chikani V, et al. J Mol Endocrinol. 2013;52:R107-R123. 3. Sacca L, et al. Endocr Rev. 1994;15:555-573. 4. Isgaard J, et al. Endocrine. 2015;48:25-35. 5. Betts JG, et al. Anatomy and Physiology 2e. OpenStax Publications. 2022. Available at: https://openstax.org/details/books/anatomy-and-physiology-2e. 6. Olarescu NC, et al. Normal Physiology of Growth Hormone in Adults. In: Pituitary Disease and Neuroendocrinology. Levy M, Korbonits M, eds. Available at: https://www.endotext.org/sections/neuroendo/. 7. Yuen KCJ, et al. Endocr Pract. 2019;25:1191-1232. 8. Stabler B, et al. Horm Res. 1996;45(1-2):30-33. 9. Leong GM, et al. Horm Res. 2003;60(suppl 1):78-85.
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You have 2 attempts left
Refer to the following and try again – Global COACH Trial Design and Rationale - slide 17 (v2.0).
1. Blum WF, et al. Endocr Connect. 2018;7:R212 R222. 2. Chikani V, et al. J Mol Endocrinol. 2013;52:R107-R123. 3. Sacca L, et al. Endocr Rev. 1994;15:555-573. 4. Isgaard J, et al. Endocrine. 2015;48:25-35. 5. Betts JG, et al. Anatomy and Physiology 2e. OpenStax Publications. 2022. Available at: https://openstax.org/details/books/anatomy-and-physiology-2e. 6. Olarescu NC, et al. Normal Physiology of Growth Hormone in Adults. In: Pituitary Disease and Neuroendocrinology. Levy M, Korbonits M, eds. Available at: https://www.endotext.org/sections/neuroendo/. 7. Yuen KCJ, et al. Endocr Pract. 2019;25:1191-1232. 8. Stabler B, et al. Horm Res. 1996;45(1-2):30-33. 9. Leong GM, et al. Horm Res. 2003;60(suppl 1):78-85.
Image generated from ChatGPT.
Mission Failed
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To Lecture Hall
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1. Blum WF, et al. Endocr Connect. 2018;7:R212 R222. 2. Chikani V, et al. J Mol Endocrinol. 2013;52:R107-R123. 3. Sacca L, et al. Endocr Rev. 1994;15:555-573. 4. Isgaard J, et al. Endocrine. 2015;48:25-35. 5. Betts JG, et al. Anatomy and Physiology 2e. OpenStax Publications. 2022. Available at: https://openstax.org/details/books/anatomy-and-physiology-2e. 6. Olarescu NC, et al. Normal Physiology of Growth Hormone in Adults. In: Pituitary Disease and Neuroendocrinology. Levy M, Korbonits M, eds. Available at: https://www.endotext.org/sections/neuroendo/. 7. Yuen KCJ, et al. Endocr Pract. 2019;25:1191-1232. 8. Stabler B, et al. Horm Res. 1996;45(1-2):30-33. 9. Leong GM, et al. Horm Res. 2003;60(suppl 1):78-85.
Image adapted from ChatGPT.
This is your final attempt
Mission failed, moving on...
Refer to the following and try again – Global COACH Trial Design and Rationale - slide 17 (v2.0).
1. Blum WF, et al. Endocr Connect. 2018;7:R212 R222. 2. Chikani V, et al. J Mol Endocrinol. 2013;52:R107-R123. 3. Sacca L, et al. Endocr Rev. 1994;15:555-573. 4. Isgaard J, et al. Endocrine. 2015;48:25-35. 5. Betts JG, et al. Anatomy and Physiology 2e. OpenStax Publications. 2022. Available at: https://openstax.org/details/books/anatomy-and-physiology-2e. 6. Olarescu NC, et al. Normal Physiology of Growth Hormone in Adults. In: Pituitary Disease and Neuroendocrinology. Levy M, Korbonits M, eds. Available at: https://www.endotext.org/sections/neuroendo/. 7. Yuen KCJ, et al. Endocr Pract. 2019;25:1191-1232. 8. Stabler B, et al. Horm Res. 1996;45(1-2):30-33. 9. Leong GM, et al. Horm Res. 2003;60(suppl 1):78-85.
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Patient Ward
Completed
Completed
Completed
Mission 4
AGV, annualized growth velocity; hGH, human growth hormone.
McDonell C, et al. Presented at: ASBMR. September 5-8, 2025. Seattle, WA. Oral Presentation 1126.
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McDonell C, et al. Presented at: ASBMR. September 5-8, 2025. Seattle, WA. Oral Presentation 1126.
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You have 2 attempts left
Refer to the following and try again – McDonell C, et al. Once-weekly lonapegsomatropin (TransCon hGH) Added to Once-weekly Navepegritide (TransCon CNP) in children with Achondroplasia: 26-week Result from the Phase 2 COACH trial. ASBMR 2025.
AGV, annualized growth velocity; hGH, human growth hormone.
McDonell C, et al. Presented at: ASBMR. September 5-8, 2025. Seattle, WA. Oral Presentation 1126.
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Mission Failed
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To Lecture Hall
Refer to the following (click on image):
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McDonell C, et al. Presented at: ASBMR. September 5-8, 2025. Seattle, WA. Oral Presentation 1126.
Image adapted from ChatGPT.
This is your final attempt
Mission failed, moving on...
Refer to the following and try again – McDonell C, et al. Once-weekly lonapegsomatropin (TransCon hGH) Added to Once-weekly Navepegritide (TransCon CNP) in children with Achondroplasia: 26-week Result from the Phase 2 COACH trial. ASBMR 2025.
AGV, annualized growth velocity; hGH, human growth hormone.
McDonell C, et al. Presented at: ASBMR. September 5-8, 2025. Seattle, WA. Oral Presentation 1126.
Image generated from ChatGPT.
Patient Ward
Completed
Completed
Completed
Completed
Continue
Compared to endogenous CNP, where might you find navepegritide’ s 38-amino acid sequence? Use this range of amino acid location as the code to open your patient’s chart.
CNP, C-type natriuretic peptide.
Carlsson Petri KC, et at: PAGE Meeting. 2024; abstr 11219.
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CNP, C-type natriuretic peptide.
Carlsson Petri KC, et at: PAGE Meeting. 2024; abstr 11219.
Image adapted from ChatGPT.
You have 2 attempts left
Compared to endogenous CNP, where might you find navepegritide’ s 38-amino acid sequence? Use this range of amino acid location as the code to open your patient’s chart.
Refer to the following and try again – Carlsson Petri KC, et al. TransCon CNP (Navepegritide): A semi-mechanistic model to describe the prolonged half-life of C-type natriuretic peptide through TransConTM technology. PAGE 2024; abstr 11219.
CNP, C-type natriuretic peptide.
Carlsson Petri KC, et at: PAGE Meeting. 2024; abstr 11219.
Image generated from ChatGPT.
Mission Failed
You are still locked in...
To Lecture Hall
Refer to the following (click on image):
Try Again
CNP, C-type natriuretic peptide.
Carlsson Petri KC, et at: PAGE Meeting. 2024; abstr 11219.
Image adapted from ChatGPT.
This is your final attempt
Mission failed, moving on...
Compared to endogenous CNP, where might you find navepegritide’ s 38-amino acid sequence? Use this range of amino acid location as the code to open your patient’s chart.
Refer to the following and try again – Carlsson Petri KC, et al. TransCon CNP (Navepegritide): A semi-mechanistic model to describe the prolonged half-life of C-type natriuretic peptide through TransConTM technology. PAGE 2024; abstr 11219.
CNP, C-type natriuretic peptide.
Carlsson Petri KC, et at: PAGE Meeting. 2024; abstr 11219.
Image generated from ChatGPT.
Ascendis Pharma. (2026). YUVIWEL® (navepegritide) for injection, for subcutaneous use [Package insert]. https://ascendispharma.us/products/pi/yuviwel/yuviwel_pi.pdf.
Image generated from ChatGPT.
Mission Failed
You are still locked in...
To Lecture Hall
Click on APPROVED LABEL
Try Again
Ascendis Pharma. (2026). YUVIWEL® (navepegritide) for injection, for subcutaneous use [Package insert]. https://ascendispharma.us/products/pi/yuviwel/yuviwel_pi.pdf.
Image adapted from ChatGPT.
You have 2 attempts left
Refer to the APPROVED LABEL.
Ascendis Pharma. (2026). YUVIWEL® (navepegritide) for injection, for subcutaneous use [Package insert]. https://ascendispharma.us/products/pi/yuviwel/yuviwel_pi.pdf.
Image generated from ChatGPT.
Mission Failed
You are still locked in...
To Lecture Hall
Click on APPROVED LABEL
Try Again
Ascendis Pharma. (2026). YUVIWEL® (navepegritide) for injection, for subcutaneous use [Package insert]. https://ascendispharma.us/products/pi/yuviwel/yuviwel_pi.pdf.
Image adapted from ChatGPT.
This is your final attempt
Mission failed, moving on...
Refer to the APPROVED LABEL.
Ascendis Pharma. (2026). YUVIWEL® (navepegritide) for injection, for subcutaneous use [Package insert]. https://ascendispharma.us/products/pi/yuviwel/yuviwel_pi.pdf.
Image generated from ChatGPT.
Patient Ward
Completed
Completed
Completed
Completed
Continue
Mission Complete
Congratulations, you have now saved Simon! You have helped this healthcare team make great progress in the treatment of children with achondorplasia.
Complete Survey
Are you sure you want to exit?
You will lose progress, and you must request access again from Global Training.
exit
Back
Your data is secured by GENIX AI
Proceed to unlock by solving a series of puzzles
or
Leave computer to explore the rest of your lab (click X to close)
Your key does not fit here
Your key does not fit here
Your key does not fit here
Your key does not fit here
Your key does not fit here
Your key does not fit here
Your key does not fit here
Your key does not fit here
Today's Lecture
Subgroup Analysis of ApproaCH, a pivotal trial with navepegritide in Achondroplasia
Presented by the Senior Medical Director of Clinical Development
You wish you had time to attend, but you are a little busy. Maybe you can use some of the lecture notes later on...
Your key does not fit here
Your key does not fit here
Your lab is secured
Enter your credentials
Your supervisor may use this information to communicate
The Staff Mailbox – With all the Center's top secret research and HIPAA concerns, it makes sense that everything is locked up!
Your key does not fit here
Your key does not fit here
Your key does not fit here
Your key does not fit here
Your key does not fit here
Your key does not fit here
Your key does not fit here
Your key does not fit here
Your key does not fit here
Your key does not fit here
Today's Lecture
Subgroup Analysis of ApproaCH, a pivotal trial with navepegritide in Achondroplasia
Presented by the Senior Medical Director of Clinical Development
You wish you had time to attend, but you are a little busy. Maybe you can use some of the lecture notes later on...
Your key does not fit here
Your key does not fit here
The Staff Mailbox – With all the Center's top secret research and HIPAA concerns, it makes sense that everything is locked up!
Lab data is secured by GENIX AI
Proceed to unlock by solving a series of puzzles
or
Leave computer to explore the rest of the lab (click X to close)
The Staff Mailbox – With all the Center's top secret research and HIPAA concerns, it makes sense that everything is locked up!
Your key does not fit here
Today's Lecture
Subgroup Analysis of ApproaCH, a pivotal trial with navepegritide in Achondroplasia
Presented by the Senior Medical Director of Clinical Development
You wish you had time to attend, but you are a little busy. Maybe you can use some of the lecture notes later on...
Your key does not fit here
Achondroplasia Escape v3
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Transcript
AchondroPlasiaEscape Game
Start
Test and apply your knowledge about achondroplasia!
The mission
You and your team are elite medical researchers at the forefront of conditions associated with genetic medicine. Simon, age 5, with achondroplasia is relying on your expertise to develop an endocrine therapy for his genetic variant to improve his quality of life. The lab’s AI system, GENIX has locked critical research data behind a series of puzzles to ensure only the most skilled researchers can access it. Your mission – should you choose to accept it – is to unlock the research data and formulate a treatment, within 3 attempts for each puzzle. How quickly you can beat other researchers in helping Simon?
Background image: Genially Hospital Lockdown example. https://view.genially.com/68f00a9fb32f660959285859/interactive-content-medical.
ASCEND Medical Center
You stroll into work, wondering what's in store for you today.
Image generated by ChatGPT.
Your Research Lab
Find the clue you need to keep moving forward
Background and book image generated from ChatGPT. Growth plate image from: Abad V, et al. Endocrinology. 2022;143:1851-7. FGF and CNP images from PubChem. FGFR3 image from Wikipedia.
Your Research Lab
Locked
Locked
Mission 1
Locked
Locked
Code used for timer is stored on last (hidden) page
Bone Tissue and Skeletal System. In Betts JG, et al. Anatomy & Physiology. OpenStax; 2013. Available at: https://openstax.org/books/anatomy-and-physiology/pages/6-introduction. Accessed October 1, 2025. Khalid K, et al. Br J Radiol. 2021;94:20210223. Image adapted from Servier Medical Art under Creative Commons Attribution 3.0 unported license.
Mission Failed
You are still locked in...
TO LECTURE HALL
Try Again
Bone Tissue and Skeletal System. In Betts JG, et al. Anatomy & Physiology. OpenStax; 2013. Available at: https://openstax.org/books/anatomy-and-physiology/pages/6-introduction. Accessed October 1, 2025. Khalid K, et al. Br J Radiol. 2021;94:20210223. Image adapted from Servier Medical Art under Creative Commons Attribution 3.0 unported license.
Background image generated by ChatGPT.
You have 2 attempts left
Bone Tissue and Skeletal System. In Betts JG, et al. Anatomy & Physiology. OpenStax; 2013. Available at: https://openstax.org/books/anatomy-and-physiology/pages/6-introduction. Accessed October 1, 2025. Khalid K, et al. Br J Radiol. 2021;94:20210223. Image adapted from Servier Medical Art under Creative Commons Attribution 3.0 unported license.
Mission Failed
You are still locked in...
TO LECTURE HALL
Try Again
Bone Tissue and Skeletal System. In Betts JG, et al. Anatomy & Physiology. OpenStax; 2013. Available at: https://openstax.org/books/anatomy-and-physiology/pages/6-introduction. Accessed October 1, 2025. Khalid K, et al. Br J Radiol. 2021;94:20210223. Image adapted from Servier Medical Art under Creative Commons Attribution 3.0 unported license.
Background image generated by ChatGPT.
This is your final attempt
Mission failed, moving on...
Bone Tissue and Skeletal System. In Betts JG, et al. Anatomy & Physiology. OpenStax; 2013. Available at: https://openstax.org/books/anatomy-and-physiology/pages/6-introduction. Accessed October 1, 2025. Khalid K, et al. Br J Radiol. 2021;94:20210223. Image adapted from Servier Medical Art under Creative Commons Attribution 3.0 unported license.
Image adapted from Pacifici M, et al. Musculoskeletal Key. Published April 14, 2020. https://musculoskeletalkey.com/the-development-growth-and-morphogenesis-of-the-skeleton/. Accessed February 18, 2026.Khalid K, et al. Br J Radiol. 2021;4:20210223.
Mission Failed
You are still locked in...
TO LECTURE HALL
Facial bones formed by intramembranous ossification (white) are typically less affected in achrondroplasia.
Try Again
Image adapted from Pacifici M, et al. Musculoskeletal Key. Published April 14, 2020. https://musculoskeletalkey.com/the-development-growth-and-morphogenesis-of-the-skeleton/. Accessed February 18, 2026.Khalid K, et al. Br J Radiol. 2021;4:20210223.
You have 2 attempts left
Image adapted from Pacifici M, et al. Musculoskeletal Key. Published April 14, 2020. https://musculoskeletalkey.com/the-development-growth-and-morphogenesis-of-the-skeleton/. Accessed February 18, 2026.Khalid K, et al. Br J Radiol. 2021;4:20210223.
Mission Failed
You are still locked in...
TO LECTURE HALL
Facial bones formed from intramembranous ossification (white) are typically less impacted in achrondroplasia.
Try Again
Image adapted from Pacifici M, et al. Musculoskeletal Key. Published April 14, 2020. https://musculoskeletalkey.com/the-development-growth-and-morphogenesis-of-the-skeleton/. Accessed February 18, 2026.Khalid K, et al. Br J Radiol. 2021;4:20210223.
This is your final attempt
Mission failed, moving on...
Image adapted from Pacifici M, et al. Musculoskeletal Key. Published April 14, 2020. https://musculoskeletalkey.com/the-development-growth-and-morphogenesis-of-the-skeleton/. Accessed February 18, 2026.Khalid K, et al. Br J Radiol. 2021;4:20210223.
Your Research Lab
Completed
Mission 2
Locked
Locked
Locked
Agirdil Y. EFORT Open Rev. 2020;5:498-507.
Image from Agirdil 2020.
Mission Failed
You are still locked in...
TO LECTURE HALL
Chondrocytes progress from a resting state to enter the phases of proliferation and hypertrophy. Under the influence of oestrogen, the proliferation of chondrocytes decreases as the resting chondrocytes are consumed. During the terminal phase of differentiation, cartilage is replaced by blood vessels and organized bone tissue, and once chondrocytes have died, the longitudinal growth of the bone ceases and the growth plate closes.
Try Again
Agirdil Y. EFORT Open Rev. 2020;5:498-507.
Background image generated by ChatGPT.
You have 2 attempts left
Agirdil Y. EFORT Open Rev. 2020;5:498-507.
Image from Agirdil 2020.
Mission Failed
You are still locked in...
TO LECTURE HALL
Chondrocytes progress from a resting state to enter the phases of proliferation and hypertrophy. Under the influence of oestrogen, the proliferation of chondrocytes decreases as the resting chondrocytes are consumed. During the terminal phase of differentiation, cartilage is replaced by blood vessels and organized bone tissue, and once chondrocytes have died, the longitudinal growth of the bone ceases and the growth plate closes.
Try Again
Agirdil Y. EFORT Open Rev. 2020;5:498-507.
Image generated by ChatGPT. Audio from Pixabay.
This is your final attempt
Mission failed, moving on...
Agirdil Y. EFORT Open Rev. 2020;5:498-507.
Image from Agirdil 2020.
FGFR3
Agirdil Y. EFORT Open Rev. 2020;5:498-507.
Image from Agirdil 2020 and https://en.wikipedia.org/wiki/Fibroblast_growth_factor_receptor_3.
Mission Failed
You are still locked in...
TO LECTURE HALL
FGFs play a critical role in regulating chondrocyte proliferation, differentiation, and hypertrophy in the growth plate. FGFs inhibit chondrocyte proliferation, thereby limiting longitudinal bone growth. Specifically, FGF is involved in chondrocyte maturation. FGFs also interact antagonistically with BMP and Ihh signaling, which promotes chondrocyte differentiation. Overexpression of FGFR3 is linked to achondroplasia.
Try Again
Agirdil Y. EFORT Open Rev. 2020;5:498-507.
Image generated by ChatGPT.
You have 2 attempts left
FGFR3
Agirdil Y. EFORT Open Rev. 2020;5:498-507.
Image from Agirdil 2020 and https://en.wikipedia.org/wiki/Fibroblast_growth_factor_receptor_3.
Mission Failed
You are still locked in...
TO LECTURE HALL
FGFs play a critical role in regulating chondrocyte proliferation, differentiation, and hypertrophy in the growth plate. FGFs inhibit chondrocyte proliferation, thereby limiting longitudinal bone growth. Specifically, FGF is involved in chondrocyte maturation. FGFs also interact antagonistically with BMP and Ihh signaling, which promotes chondrocyte differentiation. Overexpression of FGFR3 is linked to achondroplasia.
Try Again
Agirdil Y. EFORT Open Rev. 2020;5:498-507.
Image generated by ChatGPT.
This is your final attempt
Mission failed, moving on...
FGFR3
Agirdil Y. EFORT Open Rev. 2020;5:498-507.
Image from Agirdil 2020 and https://en.wikipedia.org/wiki/Fibroblast_growth_factor_receptor_3.
Your Research Lab
Completed
Mission 3
Completed
Locked
Locked
Glycine Arginine Lysine
CNP, C-type natriuretic peptide; FGFR3, fibroblast growth factor receptor 3.Rousseau F, et al. Horm Res. 1996;45:108-110. Images adapted from National Institute of Health. https://pubchem.ncbi.nlm.nih.gov/.
Mission Failed
You are still locked in...
TO LECTURE HALL
Achondroplasia is primarily caused by a specific genetic variant in the FGFR3 (Fibroblast Growth Factor Receptor 3) gene located on chromosome 4, which leads to an amino acid substitution. The most common genetic variant is a glycine to arginine substitution at position 380 of the FGFR3 protein, denoted as G380R. This mutation is a result of a G to A transition in the nucleotide sequence.
Try Again
Rousseau F, et al. Horm Res. 1996;45:108-110.
Image generated by ChatGPT. Audio from Pixabay.
You have 2 attempts left
Glycine Arginine Lysine
CNP, C-type natriuretic peptide; FGFR3, fibroblast growth factor receptor 3.Rousseau F, et al. Horm Res. 1996;45:108-110. Images adapted from National Institute of Health. https://pubchem.ncbi.nlm.nih.gov/.
Mission Failed
You are still locked in...
TO LECTURE HALL
Achondroplasia is primarily caused by a specific genetic variant in the FGFR3 (Fibroblast Growth Factor Receptor 3) gene located on chromosome 4, which leads to an amino acid substitution. The most common genetic variant is a glycine to arginine substitution at position 380 of the FGFR3 protein, denoted as G380R. This mutation is a result of a G to A transition in the nucleotide sequence.
Try Again
Rousseau F, et al. Horm Res. 1996;45:108-110.
Image generated by ChatGPT. Audio from Pixabay.
This is your final attempt
Mission failed, moving on...
Glycine Arginine Lysine
CNP, C-type natriuretic peptide; FGFR3, fibroblast growth factor receptor 3.Rousseau F, et al. Horm Res. 1996;45:108-110. Images adapted from National Institute of Health. https://pubchem.ncbi.nlm.nih.gov/.
Your Research Lab
Completed
Completed
Completed
Locked
Mission 4
CNP, C-type natriuretic peptide; FGFR3, fibroblast growth factor receptor 3. 1. Legare JM, et al. Front Pediatr. 2023;11:1229666. 2. Jurcă MC, et al. Rom J Morphol Embryol. 2021; 62:689-696. 3. Horton WA, et al. Lancet. 2007;370:162-172. 4. Rintz E, et al. Int J Mol Sci. 2022;23:5916. 5. Krejci P, et al. PLoS One. 2008;3:e3961. 6. Yasoda A, et al. Nat Med. 2004;10: 80-86. 7. Miyazawa T, et al. Endocrinology. 2002;143:3604-3610. 8. Savarirayan R, et al. Nat Rev Endocrinol. 2022;18:173-189. 9. Wrobel W, et al. Int J Mol Sci. 2021;22:5573. 10 Laederich MB, et al. Curr Opin Pediatr. 2010;22:516-523.
Mission Failed
You are still locked in...
TO LECTURE HALL
Try Again
CNP, C-type natriuretic peptide; FGFR3, fibroblast growth factor receptor 3. 1. Legare JM, et al. Front Pediatr. 2023;11:1229666. 2. Jurcă MC, et al. Rom J Morphol Embryol. 2021; 62:689-696. 3. Horton WA, et al. Lancet. 2007;370:162-172. 4. Rintz E, et al. Int J Mol Sci. 2022;23:5916. 5. Krejci P, et al. PLoS One. 2008;3:e3961. 6. Yasoda A, et al. Nat Med. 2004;10: 80-86. 7. Miyazawa T, et al. Endocrinology. 2002;143:3604-3610. 8. Savarirayan R, et al. Nat Rev Endocrinol. 2022;18:173-189. 9. Wrobel W, et al. Int J Mol Sci. 2021;22:5573. 10 Laederich MB, et al. Curr Opin Pediatr. 2010;22:516-523.
Image adapted from ChatGPT.
You have 2 attempts left
CNP, C-type natriuretic peptide; FGFR3, fibroblast growth factor receptor 3. 1. Legare JM, et al. Front Pediatr. 2023;11:1229666. 2. Jurcă MC, et al. Rom J Morphol Embryol. 2021; 62:689-696. 3. Horton WA, et al. Lancet. 2007;370:162-172. 4. Rintz E, et al. Int J Mol Sci. 2022;23:5916. 5. Krejci P, et al. PLoS One. 2008;3:e3961. 6. Yasoda A, et al. Nat Med. 2004;10: 80-86. 7. Miyazawa T, et al. Endocrinology. 2002;143:3604-3610. 8. Savarirayan R, et al. Nat Rev Endocrinol. 2022;18:173-189. 9. Wrobel W, et al. Int J Mol Sci. 2021;22:5573. 10 Laederich MB, et al. Curr Opin Pediatr. 2010;22:516-523.
Mission Failed
You are still locked in...
TO LECTURE HALL
Try Again
CNP, C-type natriuretic peptide; FGFR3, fibroblast growth factor receptor 3. 1. Legare JM, et al. Front Pediatr. 2023;11:1229666. 2. Jurcă MC, et al. Rom J Morphol Embryol. 2021; 62:689-696. 3. Horton WA, et al. Lancet. 2007;370:162-172. 4. Rintz E, et al. Int J Mol Sci. 2022;23:5916. 5. Krejci P, et al. PLoS One. 2008;3:e3961. 6. Yasoda A, et al. Nat Med. 2004;10: 80-86. 7. Miyazawa T, et al. Endocrinology. 2002;143:3604-3610. 8. Savarirayan R, et al. Nat Rev Endocrinol. 2022;18:173-189. 9. Wrobel W, et al. Int J Mol Sci. 2021;22:5573. 10 Laederich MB, et al. Curr Opin Pediatr. 2010;22:516-523.
Image adapted from ChatGPT.
This is your final attempt
Mission failed, moving on...
CNP, C-type natriuretic peptide; FGFR3, fibroblast growth factor receptor 3. 1. Legare JM, et al. Front Pediatr. 2023;11:1229666. 2. Jurcă MC, et al. Rom J Morphol Embryol. 2021; 62:689-696. 3. Horton WA, et al. Lancet. 2007;370:162-172. 4. Rintz E, et al. Int J Mol Sci. 2022;23:5916. 5. Krejci P, et al. PLoS One. 2008;3:e3961. 6. Yasoda A, et al. Nat Med. 2004;10: 80-86. 7. Miyazawa T, et al. Endocrinology. 2002;143:3604-3610. 8. Savarirayan R, et al. Nat Rev Endocrinol. 2022;18:173-189. 9. Wrobel W, et al. Int J Mol Sci. 2021;22:5573. 10 Laederich MB, et al. Curr Opin Pediatr. 2010;22:516-523.
Completada
Completada
Completada
Completada
Your Research Lab
Completed
Completed
Completed
Completed
Mission 5
Savarirayan R., et al. Nat Rev Endocrinol. 2022;18:173-189.
Mission Failed
You are still locked in...
TO LECTURE HALL
Achondroplasia is one of a small number of so-called RAMP disorders – Recurrent, Autosomal-dominant, Male-biased, Paternal age effect disorders – all of which likely arise because of their positive selective effect on spermatogonia. However, 80% of patients are born to parents of normal height. Mom and Dad do not have achondroplasia, although they are shorter than the general population. Hypochondroplasia and achondroplasia arise from a systemic fibroblast growth factor receptor 3 (FGFR3) variant, but they are distinct conditions.
Try Again
Savarirayan R., et al. Nat Rev Endocrinol. 2022;18:173-189.
Image adapted from ChatGPT.
You have 2 attempts left
Savarirayan R., et al. Nat Rev Endocrinol. 2022;18:173-189.
Mission Failed
You are still locked in...
TO LECTURE HALL
Achondroplasia is one of a small number of so-called RAMP disorders – Recurrent, Autosomal-dominant, Male-biased, Paternal age effect disorders – all of which likely arise because of their positive selective effect on spermatogonia. However, 80% of patients are born to parents of normal height. Mom and Dad do not have achondroplasia, although they are shorter than the general population. Hypochondroplasia and achondroplasia arise from a systemic fibroblast growth factor receptor 3 (FGFR3) variant, but they are distinct conditions.
Try Again
Savarirayan R., et al. Nat Rev Endocrinol. 2022;18:173-189.
Image adapted from ChatGPT.
This is your final attempt
Mission failed, moving on...
Savarirayan R., et al. Nat Rev Endocrinol. 2022;18:173-189.
Completed
Completed
Completed
Completed
Completed
Your Research Lab
Completed
Completed
Completed
Completed
Completed
Continue
Your Research Lab
Interestingly, GENIX generates a dial tone. Right away, you hear a ring from a phone booth just OUTSIDE your office! You drop everything and go check it out...
GENIX DATA UNLOCKED
You pick up the phone. "Hello? Hello?"A voice responds – "Remember the code..."
380
Continue
ASCEND Medical Center
You completed the puzzles in the Research Lab. Where's next?
Image generated by ChatGPT.
The Advanced Clinical Lab requires a numerical code to enter.
You recall that your colleague recently changed the code, and has left you a note in a locked mailbox.
Where's the Key?
Only authorized clinicians can enter the Advanced Clinical Lab. Find and grab the Key to continue.
Lab2026
I better remember this code...
Head to Clinical Lab
The Advanced Clinical Lab requires a numerical code to enter.
Enter the updated 4-digit code.
You have 2 attempts left
The Advanced Clinical Lab requires a numerical code to enter.
Enter the updated 4‑digit code (the year the U.S. Food and Drug Administration approved Yuviwel (navepegritide) for achondroplasia in pediatric patients aged two years and older with with open growth plates)
Refer to the following and try again – Note from your colleague left in the locked mailbox.
This is your final attempt
Mission failed, moving on...
The Advanced Clinical Lab requires a numerical code to enter.
Enter the updated 4‑digit code (the year the U.S. Food and Drug Administration approved Yuviwel (navepegritide) for achondroplasia in pediatric patients aged two years and older with with open growth plates)
Refer to the following and try again – Note from your colleague left in the locked mailbox.
Advanced Clinical Lab
Explore to keep moving forward
Advanced Clinical Lab
Locked
Locked
Mission 1
Locked
Locked
Locked
Match each clinical manifestation to its corresponding complication to reveal the correct code.
Complication
Foramen magnum stenosis
Hydrocephalus
Thoracolumbar kyphosis
Genu varum
Spinal (lumbar) stenosis
Sleep apnea / ear infections
Mindler GT, et al. J Child Orthop. 2024;18:461-476. Image adapted from Servier Medical Art under Creative Commons Attribution 3.0 unported license.
Mission Failed
You are still locked in...
To Lecture Hall
Refer to the following (click on image):
Try Again
Mindler GT, et al. J Child Orthop. 2024;18:461-476.
Image adapted from ChatGPT.
You have 2 attempts left
Match each clinical manifestation to its corresponding complication to reveal the correct code.
Complication
Foramen magnum stenosis
Hydrocephalus
Thoracolumbar kyphosis
Genu varum
Spinal (lumbar) stenosis
Sleep apnea / ear infections
Mindler GT, et al. J Child Orthop. 2024;18:461-476. Image adapted from Servier Medical Art under Creative Commons Attribution 3.0 unported license.
Mission Failed
You are still locked in...
To Lecture Hall
Refer to the following (click on image):
Try Again
Mindler GT, et al. J Child Orthop. 2024;18:461-476.
Image adapted from ChatGPT.
This is your final attempt
Mission failed, moving on...
Match each clinical manifestation to its corresponding complication to reveal the correct code.
Complication
Foramen magnum stenosis
Hydrocephalus
Thoracolumbar kyphosis
Genu varum
Spinal (lumbar) stenosis
Sleep apnea / ear infections
Mindler GT, et al. J Child Orthop. 2024;18:461-476. Image adapted from Servier Medical Art under Creative Commons Attribution 3.0 unported license.
Match each management option to its corresponding complication to reveal the correct code.
Complication
Clinical Manifestation
[L] Weakness, apnea, feeding issues, irritability
Foramen magnum stenosis
[D] Rapid head growth, headache, vomiting
Hydrocephalus
[R] Spinal curve ("hump") in infants
Thoracolumbar kyphosis
[I] Gait issues, pain, arthritic risk
Genu varum
[G] Leg pain, numbness, claudication, urinary issues
Spinal (lumbar) stenosis
[S] Snoring, apnea, hearing loss
Sleep apnea / ear infections
CPAP, continuous positive airway pressure; MRI, magnetic resonace imaging; VP, ventriculoperitoneal.Mindler GT, et al. J Child Orthop. 2024;18:461-476. Image adapted from Servier Medical Art under Creative Commons Attribution 3.0 unported license.
Mission Failed
You are still locked in...
To Lecture Hall
Refer to the following (click on image):
Try Again
Mindler GT, et al. J Child Orthop. 2024;18:461-476.
Image adapted from ChatGPT.
You have 2 attempts left
Match each management option to its corresponding complication to reveal the correct code.
Complication
Clinical Manifestation
[L] Weakness, apnea, feeding issues, irritability
Foramen magnum stenosis
[D] Rapid head growth, headache, vomiting
Hydrocephalus
[R] Spinal curve ("hump") in infants
Thoracolumbar kyphosis
[I] Gait issues, pain, arthritic risk
Genu varum
[G] Leg pain, numbness, claudication, urinary issues
Spinal (lumbar) stenosis
[S] Snoring, apnea, hearing loss
Sleep apnea / ear infections
CPAP, continuous positive airway pressure; MRI, magnetic resonace imaging; VP, ventriculoperitoneal.Mindler GT, et al. J Child Orthop. 2024;18:461-476. Image adapted from Servier Medical Art under Creative Commons Attribution 3.0 unported license.
Mission Failed
You are still locked in...
To Lecture Hall
Refer to the following (click on image):
Try Again
Mindler GT, et al. J Child Orthop. 2024;18:461-476.
Image adapted from ChatGPT.
This is your final attempt
Mission failed, moving on...
Match each management option to its corresponding complication to reveal the correct code.
Complication
Clinical Manifestation
[L] Weakness, apnea, feeding issues, irritability
Foramen magnum stenosis
[D] Rapid head growth, headache, vomiting
Hydrocephalus
[R] Spinal curve ("hump") in infants
Thoracolumbar kyphosis
[I] Gait issues, pain, arthritic risk
Genu varum
[G] Leg pain, numbness, claudication, urinary issues
Spinal (lumbar) stenosis
[S] Snoring, apnea, hearing loss
Sleep apnea / ear infections
CPAP, continuous positive airway pressure; MRI, magnetic resonace imaging; VP, ventriculoperitoneal.Mindler GT, et al. J Child Orthop. 2024;18:461-476. Image adapted from Servier Medical Art under Creative Commons Attribution 3.0 unported license.
Match clinical manifestation and management options to each complication to reveal the correct code.
Complication
Management Options
[C] Adenotonsillectomy, CPAP, ear tubes, audiometry, speech therapy
[S] VP shunt; neuroimaging monitoring
[M] MRI → surgical decompression
[G] Restrict sitting, bracing, spinal fusion if severe
[G] Conservative first; decompression surgery if needed
[L] Guided growth, oesteotomy; limb-lengthening rarely
Clinical Manifestation
[S] Snoring, apnea, hearing loss
[D] Rapid head growth, headache, vomiting
[L] Weakness, apnea, feeding issues, irritability
[R] Spinal curve ("hump") in infants
[G] Leg pain, numbness, claudication, urinary issues
[I] Gait issues, pain, arthritic risk
Foramen magnum stenosis
Hydrocephalus
Thoracolumbar kyphosis
Genu varum
Spinal (lumbar) stenosis
Enter the 12-character code revealed from column B (first letter, top to bottom), then column C. This corresponds to the last 12 residues of endogenous human CNP-53.
Sleep apnea / ear infections
CPAP, continuous positive airway pressure; MRI, magnetic resonace imaging; VP, ventriculoperitoneal.Nakagawa Y, et al. Biology. 2022;11:986. Image adapted from Servier Medical Art under Creative Commons Attribution 3.0 unported license.
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Nakagawa Y, et al. Biology. 2022;11:986.
Image adapted from ChatGPT.
You have 2 attempts left
Match clinical manifestation and management options to each complication to reveal the correct code.
Complication
Management Options
[C] Adenotonsillectomy, CPAP, ear tubes, audiometry, speech therapy
[S] VP shunt; neuroimaging monitoring
[M] MRI → surgical decompression
[G] Restrict sitting, bracing, spinal fusion if severe
[G] Conservative first; decompression surgery if needed
[L] Guided growth, oesteotomy; limb-lengthening rarely
Clinical Manifestation
[S] Snoring, apnea, hearing loss
[D] Rapid head growth, headache, vomiting
[L] Weakness, apnea, feeding issues, irritability
[R] Spinal curve ("hump") in infants
[G] Leg pain, numbness, claudication, urinary issues
[I] Gait issues, pain, arthritic risk
Foramen magnum stenosis
Hydrocephalus
Thoracolumbar kyphosis
Genu varum
Spinal (lumbar) stenosis
Enter the 12-character code revealed from column B (first letter, top to bottom), then column C. This corresponds to the last 12 residues of endogenous human CNP-53.
Sleep apnea / ear infections
CPAP, continuous positive airway pressure; MRI, magnetic resonace imaging; VP, ventriculoperitoneal.Nakagawa Y, et al. Biology. 2022;11:986. Image adapted from Servier Medical Art under Creative Commons Attribution 3.0 unported license.
Mission Failed
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TO LEcture Hall
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Nakagawa Y, et al. Biology. 2022;11:986.
Image adapted from ChatGPT.
This is your final attempt
Mission failed, moving on...
Match clinical manifestation and management options to each complication to reveal the correct code.
Complication
Management Options
[C] Adenotonsillectomy, CPAP, ear tubes, audiometry, speech therapy
[S] VP shunt; neuroimaging monitoring
[M] MRI → surgical decompression
[G] Restrict sitting, bracing, spinal fusion if severe
[G] Conservative first; decompression surgery if needed
[L] Guided growth, oesteotomy; limb-lengthening rarely
Clinical Manifestation
[S] Snoring, apnea, hearing loss
[D] Rapid head growth, headache, vomiting
[L] Weakness, apnea, feeding issues, irritability
[R] Spinal curve ("hump") in infants
[G] Leg pain, numbness, claudication, urinary issues
[I] Gait issues, pain, arthritic risk
Foramen magnum stenosis
Hydrocephalus
Thoracolumbar kyphosis
Genu varum
Spinal (lumbar) stenosis
Enter the 12-character code revealed from column B (first letter, top to bottom), then column C. This corresponds to the last 12 residues of endogenous human CNP-53.
Sleep apnea / ear infections
CPAP, continuous positive airway pressure; MRI, magnetic resonace imaging; VP, ventriculoperitoneal.Nakagawa Y, et al. Biology. 2022;11:986. Image adapted from Servier Medical Art under Creative Commons Attribution 3.0 unported license.
LDRIGSMSGLGC
COntinue
Nakagawa Y, et al. Biology. 2022;11:986.
Image adapted from ChatGPT.
Advanced Clinical Lab
Completed
Mission 2
Locked
Locked
Locked
Locked
Case Study
A 5-year-old child with achondroplasia has the following lower limb measurements:
Explanation: MAD is the perpendicular distance from the mechanical axis line to the center of the knee. Since it's 3.5 cm medial, the deviation is 3.5 cm medial.
Continue
Marques L. et al. EFORT Open Rev. 2021;6:487-494.
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Marques L. et al. EFORT Open Rev. 2021;6:487-494.
Image adapted from ChatGPT.
You have 2 attempts left
Case Study
A 5-year-old child with achondroplasia has the following lower limb measurements:
Explanation: MAD is the perpendicular distance from the mechanical axis line to the center of the knee. Since it's 3.5 cm medial, the deviation is 3.5 cm medial.
Continue
Marques L. et al. EFORT Open Rev. 2021;6:487-494.
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** Turn up for volume for audio description **
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Marques L. et al. EFORT Open Rev. 2021;6:487-494.
Image adapted from ChatGPT.
This is your final attempt
Mission failed, moving on...
Case Study
A 5-year-old child with achondroplasia has the following lower limb measurements:
Explanation: MAD is the perpendicular distance from the mechanical axis line to the center of the knee. Since it's 3.5 cm medial, the deviation is 3.5 cm medial.
Continue
Marques L. et al. EFORT Open Rev. 2021;6:487-494.
Image from ChatGPT.
Case Study
A 5-year-old child with achondroplasia has the following lower limb measurements:
Explanation: Fibula-to-tibia ratio = 18.5 cm / 17.0 cm ≈ 1.09
Continue
Ward LM, et al. ECE/ESPE 2025 ApproaCH Bone Morphometry Oral Presentation Slides (v2.0), slide 7.
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Ward LM, et al. ECE/ESPE 2025 ApproaCH Bone Morphometry Oral Presentation Slides (v2.0), slide 7.
Image adapted from ChatGPT.
You have 2 attempts left
Case Study
A 5-year-old child with achondroplasia has the following lower limb measurements:
Explanation: Fibula-to-tibia ratio = 18.5 cm / 17.0 cm ≈ 1.09
Continue
Ward LM, et al. ECE/ESPE 2025 ApproaCH Bone Morphometry Oral Presentation Slides (v2.0), slide 7.
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** Turn up for volume for audio description **
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Ward LM, et al. ECE/ESPE 2025 ApproaCH Bone Morphometry Oral Presentation Slides (v2.0), slide 7.
Image adapted from ChatGPT.
This is your final attempt
Mission failed, moving on...
Case Study
A 5-year-old child with achondroplasia has the following lower limb measurements:
Explanation: Fibula-to-tibia ratio = 18.5 cm / 17.0 cm ≈ 1.09
Continue
Ward LM, et al. ECE/ESPE 2025 ApproaCH Bone Morphometry Oral Presentation Slides (v2.0), slide 7.
Image from ChatGPT.
Advanced Clinical Lab
Completed
Mission 3
Completed
Locked
Locked
Locked
Case Study
A 6-year-old female named Emma, who is living with ACH, has a baseline height of 94.5 cm. Emma started Navepegritide therapy 12 months ago, and her height now is 100.8 cm. Calculate her AGV over the past year.
Continue
ACH, achondroplasia; AGV, annualized growth velocity.
1. Barstow C, et al. Am Fam Physician. 2015; 92.1: 43-50. 2. Bozzola, M, Meazza, C. (2012). Growth Velocity Curves: What They Are and How to Use Them. In: Preedy, V. (eds) Handbook of Growth and Growth Monitoring in Health and Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1795-9_180.
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1. Barstow C, et al. Am Fam Physician. 2015; 92.1: 43-50. 2. Bozzola, M, Meazza, C. (2012). Growth Velocity Curves: What They Are and How to Use Them. In: Preedy, V. (eds) Handbook of Growth and Growth Monitoring in Health and Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1795-9_180.
Image adapted from ChatGPT.
You have 2 attempts left
Case Study
A 6-year-old female named Emma, who is living with ACH, has a baseline height of 94.5 cm. Emma started Navepegritide therapy 12 months ago, and her height now is 100.8 cm. Calculate her AGV over the past year.
Continue
ACH, achondroplasia; AGV, annualized growth velocity.
1. Barstow C, et al. Am Fam Physician. 2015; 92.1: 43-50. 2. Bozzola, M, Meazza, C. (2012). Growth Velocity Curves: What They Are and How to Use Them. In: Preedy, V. (eds) Handbook of Growth and Growth Monitoring in Health and Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1795-9_180.
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1. Barstow C, et al. Am Fam Physician. 2015; 92.1: 43-50. 2. Bozzola, M, Meazza, C. (2012). Growth Velocity Curves: What They Are and How to Use Them. In: Preedy, V. (eds) Handbook of Growth and Growth Monitoring in Health and Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1795-9_180.
Image adapted from ChatGPT.
This is your final attempt
Mission failed, moving on...
Case Study
A 6-year-old female named Emma, who is living with ACH, has a baseline height of 94.5 cm. Emma started Navepegritide therapy 12 months ago, and her height now is 100.8 cm. Calculate her AGV over the past year.
Continue
ACH, achondroplasia; AGV, annualized growth velocity.
1. Barstow C, et al. Am Fam Physician. 2015; 92.1: 43-50. 2. Bozzola, M, Meazza, C. (2012). Growth Velocity Curves: What They Are and How to Use Them. In: Preedy, V. (eds) Handbook of Growth and Growth Monitoring in Health and Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1795-9_180.
1. Barstow C, et al. Am Fam Physician. 2015; 92.1: 43-50. 2. Bozzola, M, Meazza, C. (2012). Growth Velocity Curves: What They Are and How to Use Them. In: Preedy, V. (eds) Handbook of Growth and Growth Monitoring in Health and Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1795-9_180.
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Advanced Clinical Lab
Completed
Completed
Completed
Locked
Locked
Mission 4
Case Study
Patient: Isabella, 6 years old Measured Height: 96.0 cm Reference Data (CLARITY Achondroplasia Growth Chart):
Continue
SDS, standard deviation score.Hoover-Fong JE, et al. Orphanet J Rare Dis. 2021;16:522.
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Hoover-Fong JE, et al. Orphanet J Rare Dis. 2021;16:522.
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You have 2 attempts left
Case Study
Patient: Isabella, 6 years old Measured Height: 96.0 cm Reference Data (CLARITY Achondroplasia Growth Chart):
Continue
SDS, standard deviation score.Hoover-Fong JE, et al. Orphanet J Rare Dis. 2021;16:522.
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Hoover-Fong JE, et al. Orphanet J Rare Dis. 2021;16:522.
Image adapted from ChatGPT.
This is your final attempt
Mission failed, moving on...
Case Study
Patient: Isabella, 6 years old Measured Height: 96.0 cm Reference Data (CLARITY Achondroplasia Growth Chart):
Continue
SDS, standard deviation score.Hoover-Fong JE, et al. Orphanet J Rare Dis. 2021;16:522.
Image from ChatGPT.
Advanced Clinical Lab
Completed
Completed
Completed
Completed
Locked
Mission 5
Case Study
Patient: Noah, 6 years old at baseline Height: 95.0 cm Height SDS (CLARITY chart): –1.2 After 12 Months on Navepegritide Therapy:
Continue
SDS, standard deviation score.van Dommelen P, et al. Arch Dis Child. 2012;97.2:182.
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SDS, standard deviation score.van Dommelen P, et al. Arch Dis Child. 2012;97.2:182.
Image adapted from ChatGPT.
You have 2 attempts left
Case Study
Patient: Noah, 6 years old at baseline Height: 95.0 cm Height SDS (CLARITY chart): –1.2 After 12 Months on Navepegritide Therapy:
Continue
SDS, standard deviation score.van Dommelen P, et al. Arch Dis Child. 2012;97.2:182.
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Mission Failed
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SDS, standard deviation score.van Dommelen P, et al. Arch Dis Child. 2012;97.2:182.
Image adapted from ChatGPT.
This is your final attempt
Mission failed, moving on...
Case Study
Patient: Noah, 6 years old at baseline Height: 95.0 cm Height SDS (CLARITY chart): –1.2 After 12 Months on Navepegritide Therapy:
Continue
SDS, standard deviation score.van Dommelen P, et al. Arch Dis Child. 2012;97.2:182.
Image from ChatGPT.
Advanced Clinical Lab
Completed
Completed
Completed
Completed
Completed
Mission 6
Step 1 – Drag each measured domain into the correct box for the ACEM-IMPACT tool or the ACEM-Observable Signs Measure (OSM).
Measured Domain
ACEM-IMPACT Tool
ACEM-OSM Tool
Physical Functioning
Pain
EmotionalWell-Being
BalanceIssues
Daily Living Functioning
EarProblems
School
SocialFunctioning
SocialWell-Being
Sleep Apnea
Low-stamina
Step 2 – Rearrange the yellow letters on each domain in ACEM-IMPACT to decode a word related to achondroplasia
Submit
ACEM, Achondroplasia Child Experience Measure.1. Pfeiffer KM, et al. Am J Med Genet A. 2021;185:33-45. 2. Data on file. Ascendis Pharma, 2025.
Image adapted from ChatGPT. Ascendis. Global_PES_2025_ Navepegretide_Improved_Physical_Functioning_training_deck
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1. Pfeiffer KM, et al. Am J Med Genet A. 2021;185:33-45. 2. Data on file. Ascendis Pharma, 2025.
Image adapted from ChatGPT. Ascendis. Global_PES_2025_ Navepegretide_Improved_Physical_Functioning_training_deck
You have 2 attempts left
Step 1 – Drag to sort each measured domain into the correct box for ACEM-IMPACT tool vs. ACEM-Observable Signs Measure (OSM).
Measured Domain
ACEM-IMPACT Tool
ACEM-OSM Tool
Physical Functioning
Daily Living Functioning
Pain
EmotionalWell-Being
BalanceIssues
EarProblems
SocialFunctioning
School
SocialWell-Being
Sleep Apnea
Low-stamina
Step 2 – Rearrange the yellow letters on each domain in ACEM-IMPACT to decode a word related to achondroplasia
Submit
ACEM, Achondroplasia Child Experience Measure.1. Pfeiffer KM, et al. Am J Med Genet A. 2021;185:33-45. 2. Data on file. Ascendis Pharma, 2025.
Image adapted from ChatGPT. Ascendis. Global_PES_2025_ Navepegretide_Improved_Physical_Functioning_training_deck
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1. Pfeiffer KM, et al. Am J Med Genet A. 2021;185:33-45. 2. Data on file. Ascendis Pharma, 2025.
Image adapted from ChatGPT. Ascendis. Global_PES_2025_ Navepegretide_Improved_Physical_Functioning_training_deck
This is your final attempt
Mission failed, moving on...
Step 1 – Drag to sort each measured domain into the correct box for ACEM-IMPACT tool vs. ACEM-Observable Signs Measure (OSM).
Measured Domain
ACEM-IMPACT Tool
ACEM-OSM Tool
Physical Functioning
Daily Living Functioning
Pain
EmotionalWell-Being
BalanceIssues
EarProblems
SocialFunctioning
School
SocialWell-Being
Sleep Apnea
Low-stamina
Step 2 – Rearrange the yellow letters on each domain in ACEM-IMPACT to decode a word related to achondroplasia
Submit
ACEM, Achondroplasia Child Experience Measure.1. Pfeiffer KM, et al. Am J Med Genet A. 2021;185:33-45. 2. Data on file. Ascendis Pharma, 2025.
Image adapted from ChatGPT. Ascendis. Global_PES_2025_ Navepegretide_Improved_Physical_Functioning_training_deck
Advanced Clinical Lab
Completed
Completed
Completed
Completed
Completed
Completed
Continue
ASCEND Medical Center
You completed the puzzles in the Clinical Lab. Where's next?
Image generated by ChatGPT.
For the safety of our pediatric patients, the Patient Ward requires a numerical code to enter.
Enter the 3-digit code that corresponds to the highest dose of navepegritide (in mcg/kg/week) studied in our clinical trial program.
You have 2 attempts left
For the safety of our pediatric patients, the Patient Ward requires a numerical code to enter.
Enter the 3-digit code that corresponds to the highest dose of navepegritide (in mcg/kg/week) studied in our clinical trial program.
Refer to the following and try again – Breinholt VM, et al. Phase 1 safety, tolerability, pharmacokinetics and pharmacodynamics results of a long-acting C-type natriuretic peptide prodrug, TransCon CNP. Br J Clin Pharmacol. 2022;88:4763-4772.
This is your final attempt
Mission failed, moving on...
For the safety of our pediatric patients, the Patient Ward requires a numerical code to enter.
Enter the 3-digit code that corresponds to the highest dose of navepegritide (in mcg/kg/week) studied in our clinical trial program.
Refer to the following and try again – Breinholt VM, et al. Phase 1 safety, tolerability, pharmacokinetics and pharmacodynamics results of a long-acting C-type natriuretic peptide prodrug, TransCon CNP. Br J Clin Pharmacol. 2022;88:4763-4772.
Patient Ward
Mission 1
Locked
Locked
Locked
AGV, annualized growth velocity; LS, least-square.
Savarirayan R, et al. JAMA Pediatr. 2026;180:18-25.
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Mission Failed
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Refer to the following (click on image):
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Savarirayan R, et al. JAMA Pediatr. 2026;180:18-25.
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You have 2 attempts left
Refer to the following and try again – Savarirayan R, et al. Once-weekly navepegritide in children with achondroplasia: the APPROACH randomized clinical trial. JAMA Pediatr. 2026;180:18-25.
AGV, annualized growth velocity; LS, least-square.
Savarirayan R, et al. JAMA Pediatr. 2026;180:18-25.
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Mission Failed
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To Lecture Hall
Refer to the following (click on image):
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Savarirayan R, et al. JAMA Pediatr. 2026;180:18-25.
Image adapted from ChatGPT.
This is your final attempt
Mission failed, moving on...
Refer to the following and try again – Savarirayan R, et al. Once-weekly navepegritide in children with achondroplasia: the APPROACH randomized clinical trial. JAMA Pediatr. 2026;180:18-25.
AGV, annualized growth velocity; LS, least-square.
Savarirayan R, et al. JAMA Pediatr. 2026;180:18-25.
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Patient Ward
Mission 2
Locked
Completed
Locked
Savarirayan R, et al. EClinicalMedicine. 2023;65:102258.
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Mission Failed
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Refer to the following (click on image):
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Savarirayan R, et al. EClinicalMedicine. 2023;65:102258.
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You have 2 attempts left
Refer to the following and try again – Savarirayan R, et. al. Once-weekly TransCon CNP (navepegritide) in children with achondroplasia (AComplisH): a phase 2, multicentre, randomized, double-blind, placebo-controlled, dose escalation trial. EClinicalMedicine. 2023;65:102258.
Savarirayan R, et al. EClinicalMedicine. 2023;65:102258.
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Mission Failed
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Refer to the following (click on image):
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Savarirayan R, et al. EClinicalMedicine. 2023;65:102258.
Image adapted from ChatGPT.
This is your final attempt
Mission failed, moving on...
Refer to the following and try again – Savarirayan R, et. al. Once-weekly TransCon CNP (navepegritide) in children with achondroplasia (AComplisH): a phase 2, multicentre, randomized, double-blind, placebo-controlled, dose escalation trial. EClinicalMedicine. 2023;65:102258.
Savarirayan R, et al. EClinicalMedicine. 2023;65:102258.
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Patient Ward
Mission 3
Completed
Completed
Locked
1. Blum WF, et al. Endocr Connect. 2018;7:R212 R222. 2. Chikani V, et al. J Mol Endocrinol. 2013;52:R107-R123. 3. Sacca L, et al. Endocr Rev. 1994;15:555-573. 4. Isgaard J, et al. Endocrine. 2015;48:25-35. 5. Betts JG, et al. Anatomy and Physiology 2e. OpenStax Publications. 2022. Available at: https://openstax.org/details/books/anatomy-and-physiology-2e. 6. Olarescu NC, et al. Normal Physiology of Growth Hormone in Adults. In: Pituitary Disease and Neuroendocrinology. Levy M, Korbonits M, eds. Available at: https://www.endotext.org/sections/neuroendo/. 7. Yuen KCJ, et al. Endocr Pract. 2019;25:1191-1232. 8. Stabler B, et al. Horm Res. 1996;45(1-2):30-33. 9. Leong GM, et al. Horm Res. 2003;60(suppl 1):78-85.
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1. Blum WF, et al. Endocr Connect. 2018;7:R212 R222. 2. Chikani V, et al. J Mol Endocrinol. 2013;52:R107-R123. 3. Sacca L, et al. Endocr Rev. 1994;15:555-573. 4. Isgaard J, et al. Endocrine. 2015;48:25-35. 5. Betts JG, et al. Anatomy and Physiology 2e. OpenStax Publications. 2022. Available at: https://openstax.org/details/books/anatomy-and-physiology-2e. 6. Olarescu NC, et al. Normal Physiology of Growth Hormone in Adults. In: Pituitary Disease and Neuroendocrinology. Levy M, Korbonits M, eds. Available at: https://www.endotext.org/sections/neuroendo/. 7. Yuen KCJ, et al. Endocr Pract. 2019;25:1191-1232. 8. Stabler B, et al. Horm Res. 1996;45(1-2):30-33. 9. Leong GM, et al. Horm Res. 2003;60(suppl 1):78-85.
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You have 2 attempts left
Refer to the following and try again – Global COACH Trial Design and Rationale - slide 17 (v2.0).
1. Blum WF, et al. Endocr Connect. 2018;7:R212 R222. 2. Chikani V, et al. J Mol Endocrinol. 2013;52:R107-R123. 3. Sacca L, et al. Endocr Rev. 1994;15:555-573. 4. Isgaard J, et al. Endocrine. 2015;48:25-35. 5. Betts JG, et al. Anatomy and Physiology 2e. OpenStax Publications. 2022. Available at: https://openstax.org/details/books/anatomy-and-physiology-2e. 6. Olarescu NC, et al. Normal Physiology of Growth Hormone in Adults. In: Pituitary Disease and Neuroendocrinology. Levy M, Korbonits M, eds. Available at: https://www.endotext.org/sections/neuroendo/. 7. Yuen KCJ, et al. Endocr Pract. 2019;25:1191-1232. 8. Stabler B, et al. Horm Res. 1996;45(1-2):30-33. 9. Leong GM, et al. Horm Res. 2003;60(suppl 1):78-85.
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Mission Failed
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1. Blum WF, et al. Endocr Connect. 2018;7:R212 R222. 2. Chikani V, et al. J Mol Endocrinol. 2013;52:R107-R123. 3. Sacca L, et al. Endocr Rev. 1994;15:555-573. 4. Isgaard J, et al. Endocrine. 2015;48:25-35. 5. Betts JG, et al. Anatomy and Physiology 2e. OpenStax Publications. 2022. Available at: https://openstax.org/details/books/anatomy-and-physiology-2e. 6. Olarescu NC, et al. Normal Physiology of Growth Hormone in Adults. In: Pituitary Disease and Neuroendocrinology. Levy M, Korbonits M, eds. Available at: https://www.endotext.org/sections/neuroendo/. 7. Yuen KCJ, et al. Endocr Pract. 2019;25:1191-1232. 8. Stabler B, et al. Horm Res. 1996;45(1-2):30-33. 9. Leong GM, et al. Horm Res. 2003;60(suppl 1):78-85.
Image adapted from ChatGPT.
This is your final attempt
Mission failed, moving on...
Refer to the following and try again – Global COACH Trial Design and Rationale - slide 17 (v2.0).
1. Blum WF, et al. Endocr Connect. 2018;7:R212 R222. 2. Chikani V, et al. J Mol Endocrinol. 2013;52:R107-R123. 3. Sacca L, et al. Endocr Rev. 1994;15:555-573. 4. Isgaard J, et al. Endocrine. 2015;48:25-35. 5. Betts JG, et al. Anatomy and Physiology 2e. OpenStax Publications. 2022. Available at: https://openstax.org/details/books/anatomy-and-physiology-2e. 6. Olarescu NC, et al. Normal Physiology of Growth Hormone in Adults. In: Pituitary Disease and Neuroendocrinology. Levy M, Korbonits M, eds. Available at: https://www.endotext.org/sections/neuroendo/. 7. Yuen KCJ, et al. Endocr Pract. 2019;25:1191-1232. 8. Stabler B, et al. Horm Res. 1996;45(1-2):30-33. 9. Leong GM, et al. Horm Res. 2003;60(suppl 1):78-85.
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Mission 4
AGV, annualized growth velocity; hGH, human growth hormone.
McDonell C, et al. Presented at: ASBMR. September 5-8, 2025. Seattle, WA. Oral Presentation 1126.
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McDonell C, et al. Presented at: ASBMR. September 5-8, 2025. Seattle, WA. Oral Presentation 1126.
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Refer to the following and try again – McDonell C, et al. Once-weekly lonapegsomatropin (TransCon hGH) Added to Once-weekly Navepegritide (TransCon CNP) in children with Achondroplasia: 26-week Result from the Phase 2 COACH trial. ASBMR 2025.
AGV, annualized growth velocity; hGH, human growth hormone.
McDonell C, et al. Presented at: ASBMR. September 5-8, 2025. Seattle, WA. Oral Presentation 1126.
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McDonell C, et al. Presented at: ASBMR. September 5-8, 2025. Seattle, WA. Oral Presentation 1126.
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Mission failed, moving on...
Refer to the following and try again – McDonell C, et al. Once-weekly lonapegsomatropin (TransCon hGH) Added to Once-weekly Navepegritide (TransCon CNP) in children with Achondroplasia: 26-week Result from the Phase 2 COACH trial. ASBMR 2025.
AGV, annualized growth velocity; hGH, human growth hormone.
McDonell C, et al. Presented at: ASBMR. September 5-8, 2025. Seattle, WA. Oral Presentation 1126.
Image generated from ChatGPT.
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Compared to endogenous CNP, where might you find navepegritide’ s 38-amino acid sequence? Use this range of amino acid location as the code to open your patient’s chart.
CNP, C-type natriuretic peptide.
Carlsson Petri KC, et at: PAGE Meeting. 2024; abstr 11219.
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CNP, C-type natriuretic peptide.
Carlsson Petri KC, et at: PAGE Meeting. 2024; abstr 11219.
Image adapted from ChatGPT.
You have 2 attempts left
Compared to endogenous CNP, where might you find navepegritide’ s 38-amino acid sequence? Use this range of amino acid location as the code to open your patient’s chart.
Refer to the following and try again – Carlsson Petri KC, et al. TransCon CNP (Navepegritide): A semi-mechanistic model to describe the prolonged half-life of C-type natriuretic peptide through TransConTM technology. PAGE 2024; abstr 11219.
CNP, C-type natriuretic peptide.
Carlsson Petri KC, et at: PAGE Meeting. 2024; abstr 11219.
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Mission Failed
You are still locked in...
To Lecture Hall
Refer to the following (click on image):
Try Again
CNP, C-type natriuretic peptide.
Carlsson Petri KC, et at: PAGE Meeting. 2024; abstr 11219.
Image adapted from ChatGPT.
This is your final attempt
Mission failed, moving on...
Compared to endogenous CNP, where might you find navepegritide’ s 38-amino acid sequence? Use this range of amino acid location as the code to open your patient’s chart.
Refer to the following and try again – Carlsson Petri KC, et al. TransCon CNP (Navepegritide): A semi-mechanistic model to describe the prolonged half-life of C-type natriuretic peptide through TransConTM technology. PAGE 2024; abstr 11219.
CNP, C-type natriuretic peptide.
Carlsson Petri KC, et at: PAGE Meeting. 2024; abstr 11219.
Image generated from ChatGPT.
Ascendis Pharma. (2026). YUVIWEL® (navepegritide) for injection, for subcutaneous use [Package insert]. https://ascendispharma.us/products/pi/yuviwel/yuviwel_pi.pdf.
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Ascendis Pharma. (2026). YUVIWEL® (navepegritide) for injection, for subcutaneous use [Package insert]. https://ascendispharma.us/products/pi/yuviwel/yuviwel_pi.pdf.
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You have 2 attempts left
Refer to the APPROVED LABEL.
Ascendis Pharma. (2026). YUVIWEL® (navepegritide) for injection, for subcutaneous use [Package insert]. https://ascendispharma.us/products/pi/yuviwel/yuviwel_pi.pdf.
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Mission Failed
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To Lecture Hall
Click on APPROVED LABEL
Try Again
Ascendis Pharma. (2026). YUVIWEL® (navepegritide) for injection, for subcutaneous use [Package insert]. https://ascendispharma.us/products/pi/yuviwel/yuviwel_pi.pdf.
Image adapted from ChatGPT.
This is your final attempt
Mission failed, moving on...
Refer to the APPROVED LABEL.
Ascendis Pharma. (2026). YUVIWEL® (navepegritide) for injection, for subcutaneous use [Package insert]. https://ascendispharma.us/products/pi/yuviwel/yuviwel_pi.pdf.
Image generated from ChatGPT.
Patient Ward
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Subgroup Analysis of ApproaCH, a pivotal trial with navepegritide in Achondroplasia
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Today's Lecture
Subgroup Analysis of ApproaCH, a pivotal trial with navepegritide in Achondroplasia
Presented by the Senior Medical Director of Clinical Development
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The Staff Mailbox – With all the Center's top secret research and HIPAA concerns, it makes sense that everything is locked up!
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Today's Lecture
Subgroup Analysis of ApproaCH, a pivotal trial with navepegritide in Achondroplasia
Presented by the Senior Medical Director of Clinical Development
You wish you had time to attend, but you are a little busy. Maybe you can use some of the lecture notes later on...
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