Hajdu-Cheney syndrome

Hajdu-Cheney syndrome (HCS), also known as acroosteolysis with osteoporosis and changes in skull and mandible, or serpentine fibula-polycystic kidney syndrome in some overlapping phenotypes, is an extremely rare autosomal dominant skeletal disorder caused by mutations in the NOTCH2 gene. The condition is characterized by progressive acro-osteolysis (resorption of the terminal phalanges of the hands and feet), severe generalized osteoporosis with frequent fractures, and distinctive craniofacial abnormalities including wormian bones in the skull, open cranial sutures, bathrocephaly (a step-like deformity of the occipital bone), and micrognathia. Short stature is common, and affected individuals may develop basilar invagination, which can lead to serious neurological complications. The syndrome affects multiple body systems beyond the skeleton. Craniofacial features include coarse facial appearance, thick eyebrows, low-set ears, and dental abnormalities such as premature tooth loss. Cardiovascular manifestations, including patent ductus arteriosus and other congenital heart defects, have been reported. Renal cysts, hearing loss, and joint hypermobility may also occur. Neurological complications can arise from basilar invagination, potentially causing hydrocephalus, syringomyelia, or brainstem compression. The severity and progression of symptoms are highly variable, even within the same family. There is currently no cure for Hajdu-Cheney syndrome, and treatment is primarily supportive and symptom-directed. Management of osteoporosis may include bisphosphonates, though their efficacy in HCS remains uncertain and is based on limited case reports. Surgical intervention may be necessary for basilar invagination or severe skeletal complications. Regular monitoring by a multidisciplinary team including orthopedics, neurology, nephrology, and cardiology is recommended. Genetic counseling is important for affected families given the autosomal dominant inheritance pattern, though many cases arise from de novo mutations.

Common questions about Hajdu-Cheney syndrome