PHOX2B mutation-confirmed congenital central hypoventilation syndrome: presentation in adulthood.

@article{Antic2006PHOX2BMC,
  title={PHOX2B mutation-confirmed congenital central hypoventilation syndrome: presentation in adulthood.},
  author={Nick A. Antic and Beth A. Malow and Neale Lange and R Doug McEvoy and Amy L. Olson and Peter M. Turkington and Wolfram Windisch and Martin Samuels and Cathy A. Stevens and Elizabeth M Berry-Kravis and Debra E. Weese-Mayer},
  journal={American journal of respiratory and critical care medicine},
  year={2006},
  volume={174 8},
  pages={
          923-7
        }
}
Congenital central hypoventilation syndrome (CCHS) typically presents in the newborn period. A case series of five adults is presented, each heterozygous for a documented polyalanine expansion mutation in the PHOX2B gene and evidence of nocturnal alveolar hypoventilation. All cases had symptoms in childhood, but survived to adulthood without ventilatory support. After identification of physiologic compromise, artificial ventilation was initiated. These adults have the mildest of the CCHS… 
View on PubMed
normanet.ne.jp
134 Citations
Highly Influential Citations
3
Background Citations
40
Results Citations
1

134 Citations

Citation Type

Citation Type

Adult-onset congenital central hypoventilation syndrome due to PHOX2B mutation
TLDR
A 25-year-old woman with severe central hypoventilation triggered by analgesics is described, who was treated with nocturnal non-invasive ventilation and genetic analysis confirmed the diagnosis of adult-onset CCHS caused by a heterozygous de novo poly-alanine repeat expansion of the PHOX2B gene.
Congenital Central Hypoventilation Syndrome with PHOX2B Gene Mutation: Are We Missing the Diagnosis?
TLDR
A 37-old girl infant with recurrent apnea requiring repeated mechanical ventilation with no evidence of neuromuscular, cardiac or lung disease is reported and a mutation analysis of PHOX2B gene revealed 25 polyalanine repeat expansion mutation on chromosome 4p12.
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.
The genetics of congenital central hypoventilation syndrome: clinical implications
TLDR
Knowledge of the patient’s PHOX2B gene mutation helps predict a patient's clinical presentation and outcome and aids in anticipatory management of the respiratory and ANS dysfunction.
Congenital central hypoventilation syndrome: four families
TLDR
It is demonstrated that nasal mask ventilation from birth can provide adequate treatment and improved quality of life for children with CCHS and Phenotypic variability in expression of disease is seen in families with the same mutations in PHOX2B gene.
PHOX2B mutation-confirmed congenital central hypoventilation syndrome in a Chinese family: presentation from newborn to adulthood.
TLDR
A Chinese family with paired-like homeobox 2B (PHOX2B) mutation-confirmed CCHS is reported, with a clinical spectrum from newborn to adulthood, to increase awareness of its various manifestations.
Congenital central hypoventilation syndrome due to PHOX2B mutation in a Saudi child: a case report
TLDR
An autosomal-dominant inherited heterozygous pairedlike homeobox 2B (PHOX2B) gene de novo mutation has been identified in 92% to 95% of CCHS cases and encodes a highly conserved transcription factor devoted to the formation of autonomic medullary reflex pathways.
A novel missense mutation in the PHOX2Bgene is associated with late onset central hypoventilation syndrome
TLDR
The present association of LO‐CHS and HSCR in a patient harboring a rare and atypical PHOX2B mutation allows to refine the mutational spectrum of this disease and suggests individualized ventilatory care along with specific surgical and oncological approaches.
[The congenital central hypoventilation syndrome (CCHS): a late presentation].
Late-onset, insidious course and invasive treatment of congenital central hypoventilation syndrome in a case with the Phox2B mutation: case report
TLDR
Supporting the view that this gene is a master switch for the development of the autonomic nervous system network linked to respiratory control, Transgenic animals carrying the human Phox2B mutation develop a similar phenotype and lack glutamatergic neurons located in the parafacial region in the brainstem, which are involved in breathing control.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 14 REFERENCES
Congenital central hypoventilation syndrome: PHOX2B mutations and phenotype.
TLDR
These data suggest that nonpolyalanine repeat mutations produce more severe disruption of PHOX2B function and patients carrying these mutations should be evaluated for HSCR and neural crest tumors.
Adult identified with congenital central hypoventilation syndrome--mutation in PHOX2b gene and late-onset CHS.
TLDR
It is suggested that adult pulmonologists and intensivists consider the possibility of lateonset CHS, confirmable by PHOX2b assay, when caring for adults with hypercarbia of unknown etiology.
In pursuit (and discovery) of a genetic basis for congenital central hypoventilation syndrome
PHOX2B mutations and polyalanine expansions correlate with the severity of the respiratory phenotype and associated symptoms in both congenital and late onset Central Hypoventilation syndrome
TLDR
A family transmission study has shown that the risk of developing an ANSD symptom including CCHS, regarded as the most severe expression of ANS imbalance, mainly depends on the genotype at a major locus, while significant residual variants could be due to additional minor genes, modifying loci effects or environmental factors.
Molecular analysis of congenital central hypoventilation syndrome
TLDR
The prominent role of mutations in the PHOX2B gene in the pathogenesis of CCHS is confirmed and the analysis of more cases and further candidates concerned with the development of the autonomic nervous system is required.
PHOX2B genotype allows for prediction of tumor risk in congenital central hypoventilation syndrome.
TLDR
Analysis of genotype-phenotype interactions strongly supports the contention that patients with CCHS who develop malignant TSNS will harbor either a missense or a frameshift heterozygous mutation of the PHOX2B gene, highlighting the link between congenital malformations and tumor predisposition when a master gene in development is mutated.
Idiopathic congenital central hypoventilation syndrome: Analysis of genes pertinent to early autonomic nervous system embryologic development and identification of mutations in PHOX2b
Idiopathic congenital central hypoventilation syndrome (CCHS) has been linked to autonomic nervous system dysregulation and/or dysfunction (ANSD) since it was first described in 1970. A genetic basis…
Distinct pathogenetic mechanisms for PHOX2B associated polyalanine expansions and frameshift mutations in congenital central hypoventilation syndrome.
TLDR
In vitro analyses aimed at identifying the pathogenetic mechanisms which underlie the effects of PHOX2B mutations in CCHS observed that the two sets of mutations play different roles in the transcriptional regulation of these genes, showing a correlation between the length of polyalanine expansions and the severity of reduced transcriptional activity.
Idiopathic congenital central hypoventilation syndrome: diagnosis and management. American Thoracic Society.
TLDR
Infants with CCHS need to be evaluated in pediatric referral centers that have expertise in this category of abnormality both from the diagnostic and treatment perspectives, and have the interest and expertise to provide and/or coordinate the long-term followup.
Polyalanine expansion and frameshift mutations of the paired-like homeobox gene PHOX2B in congenital central hypoventilation syndrome
TLDR
An essential role of PHOX2B in the normal patterning of the autonomous ventilation system and, more generally, of the autonomic nervous system in humans is supported.
...
1
2
...