Phenotypic presentations of Hajdu-Cheney syndrome according to age - 5 distinct clinical presentations

Eur J Med Genet. 2020 Feb;63(2):103650. doi: 10.1016/j.ejmg.2019.04.007. Epub 2019 Apr 11.

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.

Keywords: Acro-osteolysis; Genetic diseases; Hajdu-Cheney syndrome; Mosaicism; NOTCH2; Osteoporosis; Rare diseases.

Publication types

  • Case Reports

MeSH terms

  • Acro-Osteolysis / congenital
  • Acro-Osteolysis / diagnostic imaging
  • Acro-Osteolysis / genetics
  • Acro-Osteolysis / physiopathology
  • Adult
  • Bone Diseases, Metabolic / congenital
  • Bone Diseases, Metabolic / genetics
  • Child
  • Exome Sequencing
  • Exons
  • Female
  • Hajdu-Cheney Syndrome / blood
  • Hajdu-Cheney Syndrome / diagnosis*
  • Hajdu-Cheney Syndrome / diagnostic imaging
  • Hajdu-Cheney Syndrome / genetics*
  • Humans
  • Male
  • Middle Aged
  • Mosaicism
  • Mutation
  • Osteoporosis / congenital
  • Osteoporosis / diagnostic imaging
  • Osteoporosis / genetics
  • Osteoporosis / physiopathology
  • Pedigree
  • Phenotype
  • Rare Diseases / genetics
  • Rare Diseases / physiopathology
  • Receptor, Notch2 / genetics*

Substances

  • NOTCH2 protein, human
  • Receptor, Notch2