Table 4.

Clinical Evaluations to Characterize CCHS Phenotype Based on PHOX2B Variant

PHOX2B VariantAnnual In-Hospital Comprehensive Testing 1Annual Neurocognitive AssessmentAnnual 72-hr Holter and ECGHirschsprung Disease AssessmentTumors of Neural Crest Origin Assessment
PARM genotype:
20/24, 20/25
PARM genotype:
20/26, 20/27
PARM genotype:
Deletion/ duplication 4XXXX2

PARM = polyalanine repeat expansion mutation with number of repeats on each allele, e.g., 20/24

NPARM = non-polyalanine repeat expansion mutation (i.e., missense, nonsense, frameshift, stop codon)

Note: In infants and those newly diagnosed with LO-CCHS the recommendation is for above-described evaluation every 6 months until age 3 years (or 3 years from the LO-CCHS diagnosis).


Awake and asleep physiologic testing in varying levels of concentration and activity simulating activities of daily living; exogenous and endogenous gas challenges; comprehensive age-appropriate clinical autonomic testing


Annual chest and abdominal imaging to identify ganglioneuromas and ganglioneuroblastomas and potentially neuroblastomas


Chest and abdominal imaging and urine cathecholamines every 3 months in the first 2 years, then every 6 months until age 7 years to identify neuroblastomas


Exon or whole-gene deletion or duplication

From: Congenital Central Hypoventilation Syndrome

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