title: Brainstem anomalies in two patients affected by congenital central hypoventilation syndrome.
abstract: Congenital central hypoventilation syndrome (CCHS) is a rare neurocristopathy characterized by absence of automatic control of respiration; decreased sensibility to hypoxia and hypercapnia, mainly during sleep; and autosomal dominant inheritance due to heterozygous polyalanine expansions and frameshift mutations in the PHOX2B gene. Because the CCHS phenotype could hide other neurologic diseases, the American Thoracic Society established that the initial evaluation of suspected CCHS should exclude neuroanatomic impairments as the structural basis of the reduced autonomic system function. In this work, we describe the clinical history of two unrelated patients with hypoventilation during sleep and harboring hypoplasia of the pons and a Chiari I malformation, respectively. In both patients, CCHS was diagnosed by detection of PHOX2B polyalanine expansion, suggesting that the American Thoracic Society diagnostic criteria may be too restrictive. Moreover, to exclude a putative role of PHOX2B in non-CCHS neurologic diseases, we have performed PHOX2B mutation screening in a group of individuals with Chiari I malformation, confirming the exclusive role of PHOX2B in the pathogenesis of CCHS.
authors.affiliation: Laboratory of Molecular Genetics, Giannina Gaslini Institute, Genoa, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Bachetti
authors.forename: Angela
authors.initials: A
authors.lastname: Robbiano
authors.forename: Sara
authors.initials: S
authors.lastname: Parodi
authors.forename: Ivana
authors.initials: I
authors.lastname: Matera
authors.forename: Elisa
authors.initials: E
authors.lastname: Merello
authors.forename: Valeria
authors.initials: V
authors.lastname: Capra
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Baglietto
authors.forename: Andrea
authors.initials: A
authors.lastname: Rossi
authors.forename: Isabella
authors.initials: I
authors.lastname: Ceccherini
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Ottonello
mesh_terms: D000328:Adult; D001933:Brain Stem / Q000002:abnormalities*; D002675:Child, Preschool; D004247:DNA / Q000032:analysis*; D003937:Diagnosis, Differential; D005260:Female; D005820:Genetic Testing / Q000379:methods; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D020182:Sleep Apnea, Central / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D018398:Homeodomain Proteins; C109220:NBPhox protein; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; D004247:DNA