Late-onset central hypoventilation syndrome: a family genetic study

Doherty, Liam S.; Kiely, John; Deegan, Paul; Nolan, Geraldine; McCabe, Steven J.; Green, Andrew J.; Ennis, Sean; McNicholas, Walter T.

doi:10.1183/09031936.00001606

Cited by 46 publications

(32 citation statements)

References 32 publications

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“…A penetração incompleta desta alteração gênica pode ocorrer em famílias; portanto, a intensidade dos sintomas pode variar. Indica-se a realização de uma avaliação genética em familiares de casos afetados para se estabelecer o risco reprodutivo e de desenvolvimento de hipoventilação alveolar 40,41 .…”

Section: Apnéia Obstrutiva Do Sonounclassified

The genetics of sleep disorders in childhood and adolescence

Nunes

Bruni

2008

J Pediatr (Rio J)

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ResumoObjetivo: O objetivo deste artigo é revisar a literatura sobre a genética dos distúrbios do sono na infância e adolescência. Fontes dos dados:As palavras-chave "sono" e "genética" foram usadas para pesquisar por artigos publicados nos últimos cinco anos no banco de dados MEDLINE. A seguir, seus resumos foram analisados. A pesquisa também incluiu artigos clássicos, com a primeira descrição dos genes. Síntese dos dados:A recorrência familiar de muitos distúrbios do sono é um achado freqüente, mas loci genéticos foram descobertos para poucos deles. Descrevemos aqui distúrbios do sono transmitidos por herança genética e também aqueles que apresentam altos índices de recorrência familiar, apesar de nenhum gene específico haver sido encontrado. Conclusões:Apesar da maioria dos distúrbios do sono ainda não terem uma base molecular identificada, técnicas modernas são cada vez mais utilizadas para determinar a contribuição dos genes ao sono e aos seus distúrbios associados. A importância clínica destas descobertas pode estar relacionada com a melhoria de métodos diagnósticos, mas também como alvo para o desenvolvimento de medicações específicas. J Pediatr (Rio J). 2008;84(4 Supl):S27-32:Sono, genética, narcolepsia, síndrome das pernas inquietas, parassônias, infância. AbstractObjective: To review the literature regarding the genetics of sleep disorders in childhood and adolescence.Sources: Articles published in the past 5 years were searched on MEDLINE using the keywords sleep and genetics. Abstracts were then analyzed. Classical articles with the first description of genes were also included. Summary of the findings:We often find familial recurrence in many sleep disorders. However, gene loci were discovered for only a

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Section: Apnéia Obstrutiva Do Sonounclassified

The genetics of sleep disorders in childhood and adolescence

Nunes

Bruni

2008

J Pediatr (Rio J)

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“…The molecular basis of CCHS was identified in 2009 and attributed to mutations in the paired-like homeobox 2B gene, PHOX2B . Two types of mutations have been described: polyalanine repeat mutations (PARMs), which are frequent, have a variable clinical presentation, and disease severity correlates with allele size; and nonpolyalanine repeat mutations (NPARMS) that are usually associated with a more severe presentation including Hirschsprung disease (HSCR) and an increased tumor risk [1,3]. Milder forms of CCHS have been also described and are due to smaller PARMs [1-6].…”

Section: Introductionmentioning

confidence: 99%

Extreme intra-familial variability of congenital central hypoventilation syndrome: a case series

2013

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IntroductionCongenital central hypoventilation syndrome is an autosomal dominant disorder that classically presents as sudden death in infancy secondary to central hypoventilation. Most cases are caused by polyalanine repeat mutations in the paired-like homeobox 2B gene, PHOX2B. More severe disease is typically associated with nonpolyalanine repeat mutations. We report the case of a family with nonpolyalanine repeat mutations that uncharacteristically has many individuals who were mildly symptomatic and only diagnosed after genetic testing. We highlight the highly variable clinical presentation of this condition and the need for clinicians to remain vigilant.Case presentationWe identified 10 individuals in a large extended Caucasian family of German and Austrian background with congenital central hypoventilation syndrome.Case 1: A 16-year old male proband presented for reproductive counseling. He had a previous history of apneic spells and Hirschsprung disease in the neonatal period. A PHOX2B nonpolyalanine repeat mutation was identified in the proband and used to screen his extended family.Cases 2 to 10: Several mildly symptomatic family members (males aged 5, 13, 42 and 80 years; females aged 28, 44, 46 and 48 years) spanning four generations were identified after genetic screening. A newborn boy from this family was also recently diagnosed with Hirschsprung disease and went on to have an abnormal sleep study.ConclusionsIn this report, we highlight the significant phenotypic variability of congenital central hypoventilation syndrome, previously thought to be a rare genetic condition. Given the extreme clinical variability, it is possible that the prevalence of congenital central hypoventilation syndrome in the general population is much higher than previous estimates. This is of major importance to all clinicians who will need to maintain a high index of suspicion for this not so rare and highly clinically variable genetic condition that spans all ages. As the familial mutation has been identified, presymptomatic and prenatal diagnostic testing are available options for family members.

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“…Cases of late-onset CCHS with pulmonary hypertension or clinically significant, persistent alveolar hypoventilation following an acute respiratory illness have been described [26][27][28][29][30]. However, the patients had subclinical or unrecognized diseases when they were children.…”

Section: Clinical Featuresmentioning

confidence: 99%