Variable phenotypes in congenital central hypoventilation syndrome with PHOX2B nonpolyalanine repeat mutations

• Published in: Journal of clinical sleep medicine Vol. 17; no. 10; pp. 2049 - 2055
• Main Authors: Kasi, Ajay S, Li, Hong, Jurgensen, Taryn J, Guglani, Lokesh, Keens, Thomas G, Perez, Iris A
• Format: Journal Article
• Language: English
• Published: United States American Academy of Sleep Medicine 01.10.2021
• Subjects: Homeodomain Proteins - genetics; Humans; Hypoventilation - congenital; Hypoventilation - genetics; Mutation; Phenotype; Retrospective Studies; Scientific Investigations; Sleep Apnea, Central - complications; Sleep Apnea, Central - genetics; Transcription Factors - genetics; congenital central hypoventilation syndrome; NPARM; CCHS; PHOX2B
• ISSN: 1550-9389; 1550-9397
• DOI: 10.5664/jcsm.9370

Congenital central hypoventilation syndrome (CCHS) is a rare disorder affecting the autonomic nervous system that is caused by variants in the paired-like homeobox 2B ( ) gene. About 10% of patients with CCHS have nonpolyalanine repeat mutations (NPARM) that are associated with severe phenotypes requiring continuous assisted ventilation, Hirschsprung's disease, and increased neural crest tumor risk. However, some patients with NPARM have milder phenotypes. Our objective was to describe the phenotypes in patients with CCHS NPARM. Retrospective case series of patients with CCHS NPARM was conducted at 2 children's hospitals to evaluate their phenotypes. We identified 8 patients with CCHS NPARM aged 3-31 years. Seven patients were diagnosed in infancy and 1 patient at 2 years of age. All patients presented with respiratory depression in the first 2 months of life. Only 1 patient was identified with a severe phenotype requiring continuous assisted ventilation, Hirschsprung's disease, and a neural crest tumor, which was resected. Five patients required positive pressure ventilation via tracheostomy only during sleep and 2 patients required oxygen only during sleep. Four patients had Hirschsprung's disease and 1 patient had a cardiac pacemaker due to a bradyarrhythmia. None of the patients had echocardiographic abnormalities. Patients with CCHS NPARM can have variable phenotypes, emphasizing the importance of implementing a plan of care that is individualized for each patient. The type of NPARM and their respective location on the gene may play a critical role in the severity of phenotypes displayed by each patient. Kasi AS, Li H, Jurgensen TJ, Guglani L, Keens TG, Perez IA. Variable phenotypes in congenital central hypoventilation syndrome with nonpolyalanine repeat mutations. . 2021;17(10):2049-2055.