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Congenital Central Hypoventilation Syndrome (congenital + central_hypoventilation_syndrome)

Distribution by Scientific Domains
Medical Sciences72%

Selected Abstracts

Congenital central hypoventilation syndrome: genotype,phenotype correlation in parents of affected children carrying a PHOX2B expansion mutation

CLINICAL GENETICS, Issue 3 2010
S Parodi
Parodi S, Vollono C, Baglietto MP, Balestri M, Di Duca M, Landri PA, Ceccherini I, Ottonello G, Cilio MR. Congenital central hypoventilation syndrome: genotype,phenotype correlation in parents of affected children carrying a PHOX2B expansion mutation. Congenital Central Hypoventilation Syndrome (CCHS) is a rare genetic disorder. Although most CCHS associated PHOX2B mutations occur de novo, about 10% of the cases are inherited from apparently asymptomatic parents, thus confirming variable expressivity and incomplete penetrance of PHOX2B mutations. Three asymptomatic parents of children affected with CCHS, and found to carry the same PHOX2B expansion mutations as their siblings, were studied by overnight polysomnography and somatic mosaicism analysis. In one case, significant sleep breathing control anomalies were detected, while the other two resulted in normal. In tissue-specific allele studies, mosaicism with a comparatively low mutant allele proportion was showed in the two unaffected adult carriers. Accurate polysomnography and assessment of the degree of somatic mosaicism should be conducted in asymptomatic carriers of PHOX2B mutations, as they may unmask subclinical but significant anomalies [source]

Congenital central hypoventilation syndrome from past to future: Model for translational and transitional autonomic medicine,

PEDIATRIC PULMONOLOGY, Issue 6 2009
Debra E. Weese-Mayer
Abstract The modern story of CCHS began in 1970 with the first description by Mellins et al., came most visibly to the public eye with the ATS Statement in 1999, and continues with increasingly fast paced advances in genetics. Affected individuals have diffuse autonomic nervous system dysregulation (ANSD). The paired-like homeobox gene PHOX2B is the disease-defining gene for CCHS; a mutation in the PHOX2B gene is requisite to the diagnosis of CCHS. Approximately 90% of individuals with the CCHS phenotype will be heterozygous for a polyalanine repeat expansion mutation (PARM); the normal allele will have 20 alanines and the affected allele will have 24,33 alanines (genotypes 20/24,20/33). The remaining ,10% of individuals with CCHS will have a non-PARM (NPARM), in the PHOX2B gene; these will be missense, nonsense, or frameshift. CCHS and PHOX2B are inherited in an autosomal dominant manner with a stable mutation. Approximately 8% of parents of a CCHS proband will be mosaic for the PHOX2B mutation. A growing number of cases of CCHS are identified after the newborn period, with presentation from infancy into adulthood. An improved understanding of the molecular basis of the PHOX2B mutations and of the PHOX2B genotype/CCHS phenotype relationship will allow physicians to anticipate the clinical phenotype for each affected individual. To best convey the remarkable history of CCHS, and to describe the value of recognizing CCHS as a model for translational and transitional autonomic medicine, we present this review article in the format of a chronological story, from 1970 to the present day. Pediatr Pulmonol. 2009; 44:521,535. © 2009 Wiley-Liss, Inc. [source]

Alcohol use in congenital central hypoventilation syndrome

PEDIATRIC PULMONOLOGY, Issue 3 2006
Maida Lynn Chen MD
Abstract Congenital central hypoventilation syndrome (CCHS) is a rare disorder where there is failure of automatic control of breathing. With improved recognition of CCHS, more children are appropriately diagnosed and treated in infancy, allowing survival into adult years. Because most of these children are able to participate in regular school, they are exposed to common adolescent behaviors, such as abusing alcohol and drugs. Alcohol and many illicit substances are known respiratory depressants. We report on 3 cases of adolescents/young adults with CCHS who had severe adverse events related to alcohol, including coma and death. This series illustrates the dangers of alcohol abuse in CCHS. We speculate that adolescents with CCHS may be less able to perceive the risks of substance abuse and impulsive behavior, leading to increased morbidity and mortality. Patients with CCHS appear to lack anxiety and the awareness that their inability to perceive physiologically dangerous levels of hypercarbia and hypoxia deprives them of important protective mechanisms. Pediatr Pulmonol. © 2006 Wiley-Liss, Inc. [source]

Congenital central hypoventilation syndrome: genotype,phenotype correlation in parents of affected children carrying a PHOX2B expansion mutation

CLINICAL GENETICS, Issue 3 2010
S Parodi
Parodi S, Vollono C, Baglietto MP, Balestri M, Di Duca M, Landri PA, Ceccherini I, Ottonello G, Cilio MR. Congenital central hypoventilation syndrome: genotype,phenotype correlation in parents of affected children carrying a PHOX2B expansion mutation. Congenital Central Hypoventilation Syndrome (CCHS) is a rare genetic disorder. Although most CCHS associated PHOX2B mutations occur de novo, about 10% of the cases are inherited from apparently asymptomatic parents, thus confirming variable expressivity and incomplete penetrance of PHOX2B mutations. Three asymptomatic parents of children affected with CCHS, and found to carry the same PHOX2B expansion mutations as their siblings, were studied by overnight polysomnography and somatic mosaicism analysis. In one case, significant sleep breathing control anomalies were detected, while the other two resulted in normal. In tissue-specific allele studies, mosaicism with a comparatively low mutant allele proportion was showed in the two unaffected adult carriers. Accurate polysomnography and assessment of the degree of somatic mosaicism should be conducted in asymptomatic carriers of PHOX2B mutations, as they may unmask subclinical but significant anomalies [source]

Alcohol use in congenital central hypoventilation syndrome

PEDIATRIC PULMONOLOGY, Issue 3 2006
Maida Lynn Chen MD
Abstract Congenital central hypoventilation syndrome (CCHS) is a rare disorder where there is failure of automatic control of breathing. With improved recognition of CCHS, more children are appropriately diagnosed and treated in infancy, allowing survival into adult years. Because most of these children are able to participate in regular school, they are exposed to common adolescent behaviors, such as abusing alcohol and drugs. Alcohol and many illicit substances are known respiratory depressants. We report on 3 cases of adolescents/young adults with CCHS who had severe adverse events related to alcohol, including coma and death. This series illustrates the dangers of alcohol abuse in CCHS. We speculate that adolescents with CCHS may be less able to perceive the risks of substance abuse and impulsive behavior, leading to increased morbidity and mortality. Patients with CCHS appear to lack anxiety and the awareness that their inability to perceive physiologically dangerous levels of hypercarbia and hypoxia deprives them of important protective mechanisms. Pediatr Pulmonol. © 2006 Wiley-Liss, Inc. [source]

Home mechanical ventilation in children: Retrospective survey of a pediatric population

PEDIATRICS INTERNATIONAL, Issue 6 2007
GIANCARLO OTTONELLO
Abstract Background: Home care support is beneficial for children needing mechanical ventilation, when clinically stable. Methods: A retrospective analysis was carried out of the long-term home ventilation management of a pediatric population with chronic respiratory failure composed of 20 ventilator-dependent children categorized according to age, diagnosis and ventilation support. Age groups consisted of 10% under 1 year, 30% between 2 and 5 years, 30% between 6 and 12 years, and 30% older than 12 years. Diagnostic categories included myopathic disorder, n = 5; congenital central hypoventilation syndrome, n = 6; chest wall disorder, n = 5; cystic fibrosis, n = 1; pulmonary hypertension, n = 1; and diaphragmatic paralysis, n = 2. Results: Sixty-five percent were ventilated using non-invasive mode (NIMV): eight with nasal mask, five with full-face mask, and two children in NIMV also used negative pressure mode; 35% were ventilated using tracheostomy, one of them also used a diaphragmatic pacer. Seventy percent needed nocturnal ventilatory support, (20% 12,18 h, 10% full-day). A total of 18 children were included in the home care and follow-up program. Two children died: one because of worsening of his chronic disease and one because of septic shock. Conclusion: Although home care ventilation is not yet widely diffused, it represents a valid alternative to long hospitalization for children with stable chronic respiratory failure. [source]

2462: Phenotype/genotype in congenital central hypoventilation syndrome

ACTA OPHTHALMOLOGICA, Issue 2010
D BREMOND-GIGNAC
Purpose To report and to classify the ocular motility disorders in congenital central hypoventilation syndrome. This rare syndrome, 1 of 200,000 livebirths, is characterized by a lack of ventilation due to defects of autonomic control especially of hypercapnia. Methods We examine in a study 34 children (range 9 days-old to 15 yo) with congenital central hypoventilation syndrome. They underwent a complete ocular and orthoptic consultation. An informed consent was signed to perform a DNA analysis to precise PHOX-2B gene mutations. Results Anisocoria, stabismus, eso and exotropia or phoria, ptosis, craniofacial palsy were found and we evaluated disorders considering intrinsic ocular motility and extrinsic ocular motility. We classified ocular anomalies in minor and major types with a score. The phenotype score was established in correlation with genotype. The score is higher in patients with genotype of equal or more 7 ALA mutations and a precise table correlation was established. Conclusion The high incidence of ocular motility disorders may result of neurologic defects of the oculomotor nerves and muscles involving neural crest development. A precise phenotype contributes to an evaluation of the severity of the disease and can also lead to a better reeducation of oculomotor anomalies. [source]

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

ACTA PAEDIATRICA, Issue 1 2009
Gabriela M Repetto
Abstract 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. [source]