Three-Generation Family With Congenital Central Hypoventilation Syndrome and Novel PHOX2B Gene Non-Polyalanine Repeat Mutation

J Clin Sleep Med. 2017 Jul 15;13(7):925-927. doi: 10.5664/jcsm.6670.

Abstract

PHOX2B non-polyalanine repeat mutation (NPARM) in patients with congenital central hypoventilation syndrome (CCHS) is generally considered to be associated with full-time ventilator dependence and severe autonomic nervous system dysfunction. We report a three-generation family with four individuals possessing a novel PHOX2B NPARM (c.245C > T) with variable phenotypes. This mutation was inherited in an autosomal dominant pattern with variable penetrance. The affected family members with CCHS have a milder phenotype than is typically expected with a NPARM. Two family members are ventilator dependent only during sleep and do not have Hirschsprung disease or neural crest tumors. One family member was asymptomatic until systemic hypertension developed during adulthood and another family member remains asymptomatic as an adult. Our findings emphasize the importance of monitoring adults with a PHOX2B NPARM who are considered asymptomatic in childhood.

Keywords: CCHS; NPARM; PHOX2B; congenital central hypoventilation syndrome.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Family
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Homeodomain Proteins / genetics*
  • Humans
  • Hypoventilation / congenital*
  • Hypoventilation / genetics
  • Hypoventilation / therapy
  • Mutation / genetics*
  • Positive-Pressure Respiration / methods
  • Sleep Apnea, Central / genetics*
  • Sleep Apnea, Central / therapy*
  • Transcription Factors / genetics*
  • Treatment Outcome

Substances

  • Homeodomain Proteins
  • NBPhox protein
  • Transcription Factors

Supplementary concepts

  • Congenital central hypoventilation syndrome