Skeletal involvement in Joubert syndrome: From low bone mineral density to severe secondary osteoporosis

Joubert syndrome (JS) is a rare ciliopathy characterized by neurological and multisystem manifestations; however, skeletal involvement remains poorly recognized. We report two genetically confirmed pediatric patients with JS illustrating different degrees of bone impairment. The first patient, a 2.5-year-old boy with a TMEM67 mutation, presented with severe hypotonia, profound immobility, multiple fractures, and markedly reduced bone mineral density (DXA Z-score -5.875), fulfilling the criteria for secondary osteoporosis and requiring bisphosphonate therapy. The second patient, a 5-year-old girl with an OFD1 mosaic mutation, showed delayed motor development and reduced bone mineral density (DXA Z-score -2.2) without fractures and was managed conservatively. These cases demonstrate the broad spectrum of skeletal manifestations in JS, ranging from low bone mineral density to severe secondary osteoporosis. Reduced mobility and chronic hypotonia may contribute to impaired bone mineralization. Increased awareness and early bone health surveillance, including fracture assessment and densitometric evaluation, may facilitate timely diagnosis and improve management of bone complications in patients with Joubert syndrome.