Síndrome de hipoventilação central congênita associada à doença de Hirschsprung: relato de caso e revisão de literatura

Sandoval, Renata Lazari; Zaconeta, Carlos Moreno; Margotto, Paulo Roberto; Cardoso, Maria Teresinha de Oliveira; França, Evely Mirella Santos; Medina, Cristina Touguinha Neves; Canó, Talyta Matos; Faria, Aline Saliba de

doi:10.1016/j.rpped.2015.10.009

Cited by 12 publications

(2 citation statements)

References 24 publications

(30 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PHOX2B also encodes a transcription factor required for normal development of the ENS ( 81 ). Genetic defects in PHOX2B have been described primarily with congenital central hypoventilation syndrome (CCHS) ( 82 ), which occur with HSCR in 15–20% of cases ( 83 ) and in some reports with neuroblastoma ( 84 , 85 ). These strongly suggest a pathogenic role of PHOX2B in HSCR.…”

Section: Pre-gwas Era: Identification Of Core Hscr Pathways Through Linkage Mapping and Candidate Gene Studies On Syndromic And Familial mentioning

confidence: 99%

The Emerging Genetic Landscape of Hirschsprung Disease and Its Potential Clinical Applications

2021

View full text Add to dashboard Cite

Hirschsprung disease (HSCR) is the leading cause of neonatal functional intestinal obstruction. It is a rare congenital disease with an incidence of one in 3,500–5,000 live births. HSCR is characterized by the absence of enteric ganglia in the distal colon, plausibly due to genetic defects perturbing the normal migration, proliferation, differentiation, and/or survival of the enteric neural crest cells as well as impaired interaction with the enteric progenitor cell niche. Early linkage analyses in Mendelian and syndromic forms of HSCR uncovered variants with large effects in major HSCR genes including RET, EDNRB, and their interacting partners in the same biological pathways. With the advances in genome-wide genotyping and next-generation sequencing technologies, there has been a remarkable progress in understanding of the genetic basis of HSCR in the past few years, with common and rare variants with small to moderate effects being uncovered. The discovery of new HSCR genes such as neuregulin and BACE2 as well as the deeper understanding of the roles and mechanisms of known HSCR genes provided solid evidence that many HSCR cases are in the form of complex polygenic/oligogenic disorder where rare variants act in the sensitized background of HSCR-associated common variants. This review summarizes the roadmap of genetic discoveries of HSCR from the earlier family-based linkage analyses to the recent population-based genome-wide analyses coupled with functional genomics, and how these discoveries facilitated our understanding of the genetic architecture of this complex disease and provide the foundation of clinical translation for precision and stratified medicine.

show abstract

Section: Pre-gwas Era: Identification Of Core Hscr Pathways Through Linkage Mapping and Candidate Gene Studies On Syndromic And Familial mentioning

confidence: 99%

The Emerging Genetic Landscape of Hirschsprung Disease and Its Potential Clinical Applications

2021

View full text Add to dashboard Cite

show abstract

“…The second described mutation has been firstly reported: even if respiratory failure at birth was probably influenced by neonatal hypoxia, the subsequent recurrent and severe apnea ad cyanosis episodes were attributable to CCHS. The presence of severe hypoglycemia associated to seizures as well as the breathing hold spells occurring also during mechanical ventilation and dysphagia were interpreted as autonomic nervous system impairment yet described in NPARMs carrier patients [11, 13, 14, 15]. As previous clinical cases with NPARMs, also the third patient had HSCR.…”

Section: Discussionmentioning

confidence: 91%

Two novel mutations in exon 3 of PHOX2B gene: think about congenital central hypoventilation syndrome in patients with Hirschsprung disease

et al. 2019

View full text Add to dashboard Cite

Background Congenital central hypoventilation syndrome (CCHS) is characterized by alveolar hypoventilation increasing during sleep and affected patients are unable to perceive and respond to hypercarbia with increased ventilation and arousal during sleep. PHOX2B gene mutations are considered as responsible for CCHS. Most of patients with CCHS are heterozygous for polyalanine expansion mutations (PARMs) in exon 3, but 10% of patients with classic CCHS are heterozygous for non-polyalanine expansion mutations (NPARMs) of the PHOX2B gene. Methods Data are collected on 3 patients affected by CCHS who referred to the Paediatric Pulmonology Unit of Bambino Gesù Children’s Hospital (Rome, Italy) for a multidisciplinary follow-up program between 2000 and 2017. Results We describe three cases of patients affected by CCHS for which two novel mutations on exon 3 of PHOX2B gene were detected. Conclusions The description of these novel mutations and related clinical phenotypes allows to expand the knowledge into NPARM spectrum. Since the presence of Hirschsprung disease is related to NPARMs and the number of alanine repeats, we suggest performing CCHS genetic investigation and periodical assessment also in patients without a clear history of CCHS but affected by Hirschsprung disease. Trial registration Data are retrospectively collected.

show abstract

Evaluation of hypoglycemia

Winter

Harris

2021

Handbook of Diagnostic Endocrinology

View full text Add to dashboard Cite

Síndrome de hipoventilação central congênita associada à doença de Hirschsprung: relato de caso e revisão de literatura

Cited by 12 publications

References 24 publications

The Emerging Genetic Landscape of Hirschsprung Disease and Its Potential Clinical Applications

The Emerging Genetic Landscape of Hirschsprung Disease and Its Potential Clinical Applications

Two novel mutations in exon 3 of PHOX2B gene: think about congenital central hypoventilation syndrome in patients with Hirschsprung disease

Evaluation of hypoglycemia

Contact Info

Product

Resources

About