Adult With PHOX2B Mutation and Late-Onset Congenital Central Hypoventilation Syndrome

J Clin Sleep Med. 2018 Dec 15;14(12):2079-2081. doi: 10.5664/jcsm.7542.

Abstract

PHOX2B 20/27 polyalanine repeat mutation (PARM) in patients with congenital central hypoventilation syndrome (CCHS) is generally associated with full-time ventilator dependence, Hirschsprung disease, and increased risk for cardiac asystole. We follow a 14-year-old boy with CCHS PHOX2B 20/27 PARM who is full-time ventilator dependent via tracheostomy and has Hirschsprung disease. His mother, age 52 years, has a history of prolonged recovery from anesthesia and an elevated serum bicarbonate level of 45 mEq/L discovered on routine blood chemistry. PHOX2B gene mutation analysis was performed and showed an identical 20/27 PARM, diagnostic of CCHS. Late-onset CCHS has been reported in those with 20/24, 20/25 PHOX2B PARM, and in nonpolyalanine repeat mutations. This is the first report of a patient with PHOX2B 20/27 PARM with a mild phenotype diagnosed during adulthood. This unusual presentation supports the screening for PHOX2B mutations in parents of children with CCHS.

Keywords: CCHS; PHOX2B; congenital central hypoventilation syndrome.

MeSH terms

  • Adolescent
  • DNA Mutational Analysis*
  • Female
  • Genetic Testing
  • Homeodomain Proteins / genetics*
  • Humans
  • Hypoventilation / congenital*
  • Hypoventilation / diagnosis
  • Hypoventilation / genetics
  • Hypoventilation / therapy
  • Male
  • Middle Aged
  • Phenotype*
  • Polysomnography
  • Positive-Pressure Respiration
  • Sleep Apnea Syndromes / diagnosis
  • Sleep Apnea Syndromes / genetics
  • Sleep Apnea Syndromes / therapy
  • Sleep Apnea, Central / diagnosis
  • Sleep Apnea, Central / genetics*
  • Sleep Apnea, Central / therapy
  • Tracheostomy
  • Transcription Factors / genetics*

Substances

  • Homeodomain Proteins
  • NBPhox protein
  • Transcription Factors

Supplementary concepts

  • Congenital central hypoventilation syndrome