Later-onset congenital central hypoventilation syndrome due to a heterozygous 24-polyalanine repeat expansion mutation in the PHOX2B gene

Aim: to describe a family with later onset congenital central hypoventilation syndrome (LO‐CCHS) and heterozygosity for a 24‐polyalanine repeat expansion mutation in the PHOX2B gene, rendered phenotypically apparent with exposure to anesthetics. Case summary: An otherwise healthy 2.75‐year‐old boy p...

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Bibliographic Details
Published in:Acta Paediatrica 2009-01, Vol.98 (1), p.192-195
Main Authors: Repetto, Gabriela M, Corrales, Raul J, Abara, Selim G, Zhou, Lili, Berry-Kravis, Elizabeth M, Rand, Casey M, Weese-Mayer, Debra E
Format: Article
Language:English
Subjects:
Age of Onset
Anesthetics
Biological and medical sciences
Central sleep apnea
Child, Preschool
Congenital central hypoventilation syndrome
DNA Mutational Analysis
General aspects
Homeodomain Proteins - genetics
Humans
Hypoventilation - genetics
Male
Medical sciences
Peptides - genetics
PHOX2B gene
Pneumology
Respiratory system : syndromes and miscellaneous diseases
Sleep Apnea, Central - congenital
Sleep Apnea, Central - surgery
Time Factors
Transcription Factors - genetics
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Summary:Aim: to describe a family with later onset congenital central hypoventilation syndrome (LO‐CCHS) and heterozygosity for a 24‐polyalanine repeat expansion mutation in the PHOX2B gene, rendered phenotypically apparent with exposure to anesthetics. Case summary: An otherwise healthy 2.75‐year‐old boy presented with alveolar hypoventilation after adenoidectomy and tonsillectomy for obstructive sleep apnea, requiring invasive ventilatory support during sleep. He had a heterozygous 24‐polyalanine repeat expansion in the PHOX2B gene (20/24 genotype), a genotype that has not been previously described in association with CCHS or LO‐CCHS symptoms. Clinical findings in members of the family with the same 20/24 genotype ranged from asymptomatic to prolonged sedation after benzodiazepines. Conclusion: CCHS should be suspected in individuals presenting with unexplained hypoventilation and/or seizures after anesthetics or sedatives. This is the first report of LO‐CCHS in a kindred with the PHOX2B 20/24 genotype. The incomplete penetrance observed in this family suggests a gene–environment interaction.
ISSN:0803-5253
1651-2227
DOI:10.1111/j.1651-2227.2008.01039.x