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

• Published in: Journal of clinical sleep medicine Vol. 13; no. 7; pp. 925 - 927
• Main Authors: Kasi, Ajay S, Jurgensen, Taryn J, Yen, Stephanie, Kun, Sheila S, Keens, Thomas G, Perez, Iris A
• Format: Journal Article
• Language: English
• Published: United States American Academy of Sleep Medicine 15-07-2017
• Subjects: Case Reports; congenital central hypoventilation syndrome; NPARM; CCHS; PHOX2B
• ISSN: 1550-9389; 1550-9397
• DOI: 10.5664/jcsm.6670

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
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
NPARM who are considered asymptomatic in childhood.