title: Heterozygous 24-polyalanine repeats in the PHOX2B gene with different manifestations across three generations.
abstract: Congenital central hypoventilation syndrome (CCHS) is an uncommon genetic disorder that is characterized by alveolar hypoventilation and autonomic dysregulation. More than 90% of the patients are heterozygous for polyalanine repeat expansion mutations in the paired-like homeobox 2b (PHOX2B) gene. The normal genotype has a 20-polyalanine sequence whereas expanded alleles are usually 25-33. Heterozygous 24-polyalanine repeat expansion mutation in the PHOX2B gene has rarely been reported. We report three consecutive generations harboring heterozygous 24-polyalanine repeats in the PHOX2B gene with manifestations ranging from apparently asymptomatic to alveolar hypoventilation and apnea requiring mechanical ventilation. The 3-year-old proband developed cor pulmonale and central hypoventilation following an upper respiratory tract infection. Our findings add to the accumulating evidence that the 24-polyalanine repeat in the PHOX2B is a disease-causing mutation. In addition, a high index of suspicion and careful monitoring after anesthesia, sedation, or respiratory illnesses should be exercised when evaluating asymptomatic family members with this genotype.
authors: Department of Pediatrics, Washington University School of Medicine in St. Louis, St. Louis, Missouri.
authors: Piyaporn
authors: P
authors: Chuen-im
authors: Shinawi
authors: S
authors: Marwan
authors: Jodi
authors: J
authors: Carter
authors: James
authors: J
authors: Kemp
authors: Katherine
authors: K
authors: Rivera-Spoljaric
mesh_terms: D000328:Adult; D002675:Child, Preschool; D042622:DNA Repeat Expansion; D005260:Female; D005819:Genetic Markers; D006579:Heterozygote; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007040:Hypoventilation / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics; D010455:Peptides / Q000235:genetics*; D020182:Sleep Apnea, Central / Q000175:diagnosis / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D018398:Homeodomain Proteins; C109220:NBPhox protein; D010455:Peptides; D014157:Transcription Factors; C019529:polyalanine
keywords: PHOX2B; central hypoventilation syndrome; cor pulmonale