Germline mosaicism of PHOX2B mutation accounts for familial recurrence of congenital central hypoventilation syndrome (CCHS)

@article{Rand2012GermlineMO,
  title={Germline mosaicism of PHOX2B mutation accounts for familial recurrence of congenital central hypoventilation syndrome (CCHS)},
  author={Casey M. Rand and Min Yu and Lawrence Jennings and Kelvin Panesar and Elizabeth M Berry-Kravis and Lili Zhou and Debra E. Weese-Mayer},
  journal={American Journal of Medical Genetics Part A},
  year={2012},
  volume={158A}
}
Congenital central hypoventilation syndrome (CCHS), a rare disorder characterized by alveolar hypoventilation and autonomic dysregulation, is caused by mutations in the PHOX2B gene. Most mutations occur de novo, but recent evidence suggests that up to 25% are inherited from asymptomatic parents with somatic mosaicism for these mutations. However, to date, germline mosaicism has not been reported. This report describes a family with recurrence of PHOX2B mutation‐confirmed CCHS due to germline… 
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Causative and common PHOX2B variants define a broad phenotypic spectrum
TLDR
The role of PHOX2B in the ANS development, causative mutations, common variants, and gene expression deregulation of the PHOx2B gene are discussed, though the involvement of synonymous variants and contractions requires further confirmations with respect to ANS disorders and molecular mechanisms underlying the PHOX1B phenotypic heterogeneity.
Congenital central hypoventilation syndrome: Severe disease caused by co‐occurrence of two PHOX2B variants inherited separately from asymptomatic family members
TLDR
A co‐occurrence of two asymptomatic PHOx2B variants with a classical CCHS presentation highlights the importance of clinical PHOX2B testing in parents and family members of all CCHs probands.
Mutations in MYO1H cause a recessive form of central hypoventilation with autonomic dysfunction
TLDR
The results identify MYO1H as an important gene in CO2 sensitivity and respiratory control and as the cause of a rare recessive form of congenital central hypoventilation with autonomic dysfunction.
Recurrence of CCHS associated PHOX2B poly‐alanine expansion mutation due to maternal mosaicism
TLDR
A CCHS patient, carrying a +13Ala PHOX2B expansion, whose asymptomatic mother resulted with a low level of mosaicism for the same mutation in peripheral blood cells is reported, confirming germline mosaicism in the mother and the need of proper genetic counseling to CCHs families.
A respiratory/Hirschsprung phenotype in a three‐generation family associated with a novel pathogenic PHOX2B splice donor mutation
TLDR
Mutations in the PHOX2B gene cause congenital central hypoventilation syndrome, a rare autonomic nervous system dysfunction disorder characterized by a decreased ventilatory response to hypercapnia, and is associated with disorders characterized by the defective migration/differentiation of neural crest derivatives, including aganglionic megacolon or milder gastrointestinal phenotypes, such as constipation.
Rare cause of neonatal apnea from congenital central hypoventilation syndrome
TLDR
Diagnosis of CCHS in neonates includes the main clue of the absence of hypercapnic ventilatory response which worsens during non-rapid eye movement (NREM) sleep after exclusion of other causes.
Guidelines for diagnosis and management of congenital central hypoventilation syndrome
TLDR
A state-of-the-art comprehensive description of CCHS and of the components of diagnostic evaluation and multi-disciplinary management, as well as considerations for future research are provided.
Hypoventilation Syndromes of Infancy, Childhood, and Adulthood: Congenital Central Hypoventilation Syndrome (CCHS), Later-Onset CCHS, and Rapid-Onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation
A case of congenital central hypoventilation syndrome in a three‐generation family with non‐polyalanine repeat PHOX2B mutation
We describe a three generation family in whom multiple individuals are variably affected due to a PHOX2B non‐polyalanine repeat mutation. This family demonstrates extreme phenotypic variability and…
Congenital central hypoventilation syndrome and sudden infant death syndrome: disorders of autonomic regulation.
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References

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TLDR
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TLDR
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TLDR
Two families in which a PHOX2b defect was inherited from an asymptomatic parent are reported, suggesting that germline mosaicism may lead to CCHS in children from unaffected parents.
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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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