Context: Mutations in the cathepsin K gene (CTSK) cause a very rare form of short-limb dwarfism called pyknodysostosis (online inheritance in man 265800) that reduces adult height to 130-150 cm.
Objective: To study the effects of GH in children with pyknodysostosis.
Design and methods: This was a pilot open study of three children with pyknodysostosis (P1, P2, P3) and 16 age-matched children with idiopathic short stature (ISS) treated with a similar IGF-I-based dosing of GH therapy. P1, P2, and P3 received a mean GH dose of 29, 67, and 120 microg/kg x d, respectively, during 12, 6.5, and 5 yr, whereas the ISS group received a mean dose of 62 +/- 21 microg/kg x d during 5.4 +/- 2 yr.
Results: P1, P2, and P3 had the typical clinical and radiological features of pyknodysostosis. They were shown to carry three different homozygous missense mutations of the CTSK gene. After onset of GH at 4.5, 5.4, and 10.9 yr of age, respectively, height increased from -2, -4.2, and -3 SD score to -1, -0.5, and -1 SD score after a 12, 6.5, and 5 yr GH treatment. Remarkably, body disproportion was largely corrected by GH treatment. IGF-I levels in P1, P2, and P3 were within the range of the ISS group.
Conclusions: Pyknodysostotic patients can reach near-normal stature and skeletal proportions with a personalized GH treatment targeted at appropriate IGF-I levels. Given the severity of this rare dwarfism, we propose that GH should be offered to affected children.