A Further Case of Hajdu-Cheney Syndrome Having a Novel Mutation in the NOTCH2 Gene

Hajdu-Cheney syndrome (HCS) is a very rare, autosomal dominant syndrome characterized by acroosteolysis of distal phalanges, generalized osteoporosis often leading to multiple fractures, craniofacial and dental abnormalities, and proportionate short stature. It was first described by Hajdu and Kauntze (1948) and Cheney (1965). In 2011, several groups identified mutations in the NOTCH2 gene, located on chromosome 1 which was responsible for HCS. Most cases of HCS are sporadic, but rare familial forms with autosomal dominant mode of inheritance have been described. We describe here a 35-year-old male patient who had a novel mutation in exon 34 of the NOTCH2 gene. The patient exhibited typical facial features including hypertelorism, bushy eyebrows, long philtrum, micrognatia, dental anomalies, low-set ears, full cheeks, short neck, and short fingers. X-ray studies showed Wormian bones in the skull, acro-osteolysis of distal phalanges, and short, bowed long bones. On echocardiography, minimal mitral and aortic regurgitation were observed. Odiological examination revealed a conductive hearing loss. Regarding clinical findings, he was considered to have Hajdu-Cheney syndrome. Molecular analysis showed a heterozygous truncating c.6616 G>T (p.E2206X) mutation in the last exon of the NOTCH2 gene. This Hajdu-Cheney case with a novel mutation is the first case whose molecular diagnosis was performed in Turkey and may help to establish phenotype-genotype correlation in the syndrome.