ABSTRACT
We present five Danish individuals with Hajdu-Cheney syndrome (HJCYS) (OMIM #102500), a rare multisystem skeletal disorder with distinctive facies, generalised osteoporosis and progressive focal bone destruction. In four cases positive genetic screening of exon 34 of NOTCH2 supported the clinical diagnosis; in one of these cases, mosaicism was demonstrated, which, to our knowledge, has not previously been reported. In one case no genetic testing was performed since the phenotype was definite, and the diagnosis in the mother was genetically confirmed. The age of the patients differs widely from ten to 57 years, allowing a natural history description of the phenotype associated with this ultra-rare condition. The evolution of the condition is most apparent in the incremental bone loss leading to osteoporosis and the acro-osteolysis, both of which contribute significantly to disease burden.
Subject(s)
Hajdu-Cheney Syndrome/diagnosis , Hajdu-Cheney Syndrome/genetics , Receptor, Notch2/genetics , Acro-Osteolysis/congenital , Acro-Osteolysis/diagnostic imaging , Acro-Osteolysis/genetics , Acro-Osteolysis/physiopathology , Adult , Bone Diseases, Metabolic/congenital , Bone Diseases, Metabolic/genetics , Child , Exons , Female , Hajdu-Cheney Syndrome/blood , Hajdu-Cheney Syndrome/diagnostic imaging , Humans , Male , Middle Aged , Mosaicism , Mutation , Osteoporosis/congenital , Osteoporosis/diagnostic imaging , Osteoporosis/genetics , Osteoporosis/physiopathology , Pedigree , Phenotype , Rare Diseases/genetics , Rare Diseases/physiopathology , Exome SequencingABSTRACT
Hajdu-Cheney syndrome is an autosomal dominant disorder characterized by acroosteolysis of the distal phalanges associated with digit abnormalities, distinctive craniofacial changes, dental anomalies, and a proportionate short stature. The pubertal development of children with Hajdu-Cheney syndrome is usually normal in the literature, although we here first describe a girl who was found to have Hajdu-Cheney syndrome accompanied with premature ovarian failure. She showed a follicle-stimulating hormone-dominant response on luteinizing hormone-releasing hormone test and did not show any sex differentiation abnormality or adrenal steroid hormone deficiency. On the basis of the findings in our patient, premature ovarian failure may be a complication of Hajdu-Cheney syndrome and thus an early endocrinological evaluation of patients is important.
