Table 2.

Select Features of Congenital Central Hypoventilation Syndrome by PARM vs NPARM and PARM Genotype

FeatureGenotype
PARM genotypeNPARMs
20/24, 1 20/2520/2620/27NPARM in general38-bp deletion
Respiratory
(hypoventilation)		Asleep onlyAwake w/exertion & eating & asleepAwake & asleepAwake & asleepAwake & asleep
Cardiac arrhythmia:
Abrupt sinus pauses ≥3 sec warranting cardiac pacemaker		Variable: none w/childhood onset; subset will have prolonged sinus pauses in adulthood19%>80%None w/childhood onset to date
Hirschsprung disease<0.1%20%-30%80%-90%95%-100% severe long segment disease (i.e., entire colon & some small intestine)
Severe constipation~≥50%
Esophageal dysmotility/dysphagia1st yr of life
Neural crest tumorsNeuroblastoma0%0%See footnote 2.50%
Ganglio-
neuroblastoma		0%0%0%<5%
Ganglioneuroma0%0%0%<5%
ANSD:
Pupillary response to light		Normal responseMidsize pupils w/attenuated response to lightSmall pupils at rest; nearly absent response to lightLarge pupils at rest; negligible response to light

ANSD = autonomic nervous system dysregulation; NPARM = non-polyalanine repeat expansion mutation (i.e., missense, nonsense, frameshift, stop codon, splice site); PARM = polyalanine repeat expansion mutation

1.

Genotype 20/24 would be considered a susceptibility allele (needs another factor to manifest) or a low- or variable-penetrance allele with features that can be triggered by pharmacologic agents (a pharmaco-genetic phenomenon), or a gene x environment interaction (without main effects).

2.

Generally 0%; however, an infant with the 20/33 genotype had metastatic neuroblastoma [Armstrong et al 2015].

From: Congenital Central Hypoventilation Syndrome

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