Hajdu-Cheney Syndrome as a Rare Cause of Acroosteolysis: A Case Report

Hajdu-Cheney syndrome (HCS) is a rare autosomal dominant multisystem disorder caused by mutations in the NOTCH2 gene, leading to dysregulation of the Notch signaling pathway. It is characterized by a broad and variable clinical spectrum, including acroosteolysis, osteoporosis, short stature, craniofacial dysmorphism, and potential cardiovascular, renal, and neurological involvement. We report the case of a 16-year-old boy, born to consanguineous parents, who was referred for evaluation of facial dysmorphism. Clinical examination revealed typical features of HCS, including brachycephaly with a prominent occiput, hypertelorism with telecanthus, low-set ears, long philtrum, micrognathia, thick hair and eyebrows, periodontal disease with early tooth loss, brachydactyly with pseudo-clubbing, and pectus carinatum. The patient had a history of surgically treated patent ductus arteriosus. Radiological investigations showed kyphoscoliosis, generalized osteoporosis with multiple fractures, delayed closure of cranial sutures, an enlarged J-shaped sella turcica, and transverse acroosteolysis of the distal phalanges. Brain MRI revealed basilar invagination with compression of the acoustic-facial nerve bundle, explaining progressive bilateral hearing loss. Laboratory findings were within normal limits, with no abnormalities in calcium-phosphate metabolism or inflammatory markers. Whole-exome sequencing identified a heterozygous nonsense mutation in the NOTCH2 gene (NM_024408.4.6484del), classified as likely pathogenic, confirming the diagnosis of HCS. The patient was treated with IV zoledronic acid every six months, along with calcium and vitamin D supplementation. This case illustrates the multisystem and highly variable presentation of HCS. The combination of characteristic skeletal, craniofacial, neurological, and cardiovascular features associated with a de novo NOTCH2 mutation broadens the clinical spectrum of this exceptionally rare disorder. Advances in understanding the role of Notch signaling may lead to targeted therapies in the future. Prognosis depends on the severity of systemic complications, particularly neurological involvement and thoracic deformities leading to respiratory impairment.