NOTCH2 related disorders: Description and review of the fetal presentation

Eur J Med Genet. 2023 Jul;66(7):104769. doi: 10.1016/j.ejmg.2023.104769. Epub 2023 Apr 28.

Abstract

Signs of skeletal dysplasias are relatively common in fetuses with abnormal ultrasound (US) findings. The diversity of congenital skeletal disorders, the possibility of late-onset severe phenotypes and overlapping syndromes can be a challenge in the way of diagnosis, even if prenatal high-throuput sequencing allows for a better diagnosis, prognosis and genetic counseling. Hajdu-Cheney spectrum pathologies are rarely described in prenatal, and the signs associated remain poorly known, and do not include specific postnatal signs as acro-osteolysis and premature osteoporosis. We hereby report a couple for whom a medical termination of pregnancy was performed because a severe polymalformative syndrome associating severely short limbs with bowed long bones, severe cardiopathy, hyperechogenic kidneys and dysmorphism. After fetopathological and radiological examinations, Exome Sequencing (ES) was performed and revealed a de novo truncating mutation in the last exon of NOTCH2, responsible for Hajdu-Cheney or Serpentine Fibula Polycystic Kidney syndromes.

Publication types

  • Review

MeSH terms

  • Acro-Osteolysis* / genetics
  • Exons
  • Female
  • Hajdu-Cheney Syndrome* / diagnostic imaging
  • Hajdu-Cheney Syndrome* / genetics
  • Humans
  • Labor Presentation
  • Osteoporosis* / genetics
  • Pregnancy
  • Receptor, Notch2 / genetics

Substances

  • NOTCH2 protein, human
  • Receptor, Notch2