Pycnodysostosis: A Case Series of Eight Saudi Patients with Cathepsin K Gene Mutation and a Literature Review

Afaf Alsaghier ^1* Raghad Alhuthil ¹ Ahmad T Alissa ² Faisal Muhieddine Joueidi ² Ahmed G Sayed ² Waleed Al-Amoudi ² Alanoud S Al Abdulhadi ² Bassam Bin-Abbas ^1*

• ¹ King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
• ² Alfaisal University, Riyadh, Saudi Arabia

Pycnodysostosis, a rare osteopetrosis subtype, is mainly caused by homozygous or compound heterozygous biallelic pathogenic mutation of the cathepsin K (CTSK) gene. The cohort included eight patients (four males and four females) with a mean current age of 13 years (SD ± 3.6) and a mean age at diagnosis of 5 years (SD ± 2). All patients had a positive family history of pycnodysostosis and were born to consanguineous parents. Genetic analysis revealed that all individuals carried the same mutation: NM_000396.3(CTSK):c.244-29A>G. Clinically, they exhibited characteristic craniofacial features and skeletal deformities consistent with the diagnosis.Bone fractures were reported in 7 out of 8 patients, highlighting a significant clinical burden. All affected individuals received growth hormone therapy(GHT), though response to treatment varied among the group.These findings emphasize the importance of early genetic screening, particularly in families with a known history of pycnodysostosis, to enable timely diagnosis and intervention. Although pycnodysostosis is typically described as a nonprogressive skeletal dysplasia, the presence of complications such as osteomyelitis and recurrent fractures may contribute to a more complex and progressive clinical course in some patients.