Hajdu-Cheney Syndrome, a Rare Cause of Acro-Osteolysis and Osteoporosis With Zoledronic Acid Experience

Hajdu-Cheney syndrome (HCS), caused by a heterozygous gain of function variant of the NOTCH2 gene, is a rare skeletal dysplasia. Although the main presentation is acro-osteolysis, osteoporosis, and facial dysmorphism, having a wide range of clinical manifestations creates diagnostic difficulties. Here, a 15-year-old male patient with HCS who had no complaints until this age except for two short bone fractures and one vertebral collapse fracture due to a fall was reported. The patient presented with acro-osteolysis, facial anomalies, skull deformity, and osteoporosis. The clinical diagnosis of HCS was supported by a positive genetic test of a novel de novo heterozygous pathogenic variant in exon 34 of NOTCH2 c.6614dupAfs*. Zoledronic acid treatment was applied for 2 years, and the patient responded well to the treatment, showing signs of improved bone density and improvement in vertebral height. We identified a novel NOTCH2 gene variant related to HCS. Our findings could extend phenotypic spectrum and genotype-phenotype correlations. The results of this case report support that antiresorptive treatment with zoledronic acid increased bone mineral density. Nevertheless, because of the low prevalence of the syndrome and the small number of reported cases, further studies are required to understand the syndrome better and establish treatment guidelines.