Congenital central hypoventilation syndrome without hypoventilation: is it congenital central hypoventilation syndrome? 2023

Laura Lazzarini Wo, and Reem Itani, and Thomas G Keens, and Araz Marachelian, and Jianling Ji, and Iris A Perez
Division of Pulmonology and Sleep Medicine, Children's Hospital Los Angeles, Los Angeles, California.

Congenital central hypoventilation syndrome (CCHS) is a rare condition caused by pathogenic variants of the PHOX2B gene. There have been case reports describing variable phenotypes and mutations of the PHOX2B gene, not commonly tested for, that may challenge the classic definition of CCHS. We report on 3 family members with a rare heterozygous deletion encompassing the entire PHOX2B gene with variable phenotypes, including sleep-disordered breathing and autonomic nervous system involvement, but an unexpected lack of alveolar hypoventilation, which is usually a defining feature of CCHS. Our cases highlight the dilemmas in making a diagnosis of CCHS and emphasize the need for expanded genetic testing, including for PHOX2B gene deletion. More patients with variable phenotypes of CCHS may be identified through comprehensive genetic testing and warrant surveillance as they are still at risk for high-risk complications of CCHS. Wo LL, Itani R, Keens TG, Marachelian A, Ji J, Perez IA. Congenital central hypoventilation syndrome without hypoventilation: is it congenital central hypoventilation syndrome? J Clin Sleep Med. 2023;19(6):1161-1164.

UI MeSH Term Description Entries
D007040 Hypoventilation A reduction in the amount of air entering the pulmonary alveoli. Hypoventilations
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014157 Transcription Factors Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. Transcription Factor,Factor, Transcription,Factors, Transcription
D018398 Homeodomain Proteins Proteins encoded by homeobox genes (GENES, HOMEOBOX) that exhibit structural similarity to certain prokaryotic and eukaryotic DNA-binding proteins. Homeodomain proteins are involved in the control of gene expression during morphogenesis and development (GENE EXPRESSION REGULATION, DEVELOPMENTAL). Homeo Domain Protein,Homeobox Protein,Homeobox Proteins,Homeodomain Protein,Homeoprotein,Homeoproteins,Homeotic Protein,Homeo Domain Proteins,Homeotic Proteins,Domain Protein, Homeo,Protein, Homeo Domain,Protein, Homeobox,Protein, Homeodomain,Protein, Homeotic,Proteins, Homeo Domain,Proteins, Homeobox,Proteins, Homeodomain,Proteins, Homeotic
D020182 Sleep Apnea, Central A condition associated with multiple episodes of sleep apnea which are distinguished from obstructive sleep apnea (SLEEP APNEA, OBSTRUCTIVE) by the complete cessation of efforts to breathe. This disorder is associated with dysfunction of central nervous system centers that regulate respiration. Apnea, Sleep, Central,Central Sleep Apnea,Hypoventilation, Central Alveolar,Ondine Syndrome,Sleep-Disordered Breathing, Central,Apnea, Central,Apnea, Central Sleep,Central Alveolar Hypoventilation Syndrome,Central Sleep Apnea Syndrome,Central Sleep Apnea, Primary,Central Sleep Apnea, Secondary,Central Sleep Disordered Breathing,Newborn Primary Sleep Apneas,Primary Central Sleep Apnea,Primary Sleep Apneas of Newborn,Secondary Central Sleep Apnea,Sleep Apnea, Lethal Central,Sleep Apnea, Newborn, Primary,Alveolar Hypoventilation, Central,Alveolar Hypoventilations, Central,Apneas, Central,Apneas, Central Sleep,Breathing, Central Sleep-Disordered,Breathings, Central Sleep-Disordered,Central Alveolar Hypoventilation,Central Apnea,Central Apneas,Central Sleep Apneas,Central Sleep-Disordered Breathing,Central Sleep-Disordered Breathings,Hypoventilations, Central Alveolar,Sleep Apneas, Central,Sleep Disordered Breathing, Central,Sleep-Disordered Breathings, Central

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