Diagnostic Test Directory

Molecular Genetics Laboratory

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Neuroblastoma / Classic Congenital Central Hypoventilation Syndrome,CCHS (PHOX2B Known Mutation)

  • LIS Mnemonic: MBPHOX2BKM


    Collect whole blood in a purple top (EDTA) tube (preferred). Extracted DNA is also acceptable.

    Volume Required

    5 ml whole blood or 1 ug DNA

    Minimum Required

    3 ml whole blood


    Refrigerate sample until shipment. Send the sample at room temperature with overnight delivery for receipt Monday through Friday within 24 hours of collection.


    Whole blood can be refrigerated until shipment.

    Unacceptable conditions

    Heparinized specimens, severely hemolyzed specimens, frozen, clotted or possibly commingled specimens, blood in non-sterile or leaky containers, mislabeled or inappropriately labeled specimens.

    Specimen Handling

    Do not heat, freeze or centrifuge blood before shipment. Refrigerate sample until shipment.

Days Performed

Mon - Fri 9:00am to 4:00pm


2-3 weeks



Disease Information

Clinical Features:

Classic congenital central hypoventilation syndrome (CCHS) is characterized by adequate ventilation while the affected individual is awake and by hypoventilation with normal respiratory rates and shallow breathing during sleep; more severely affected individuals hypoventilate when both awake and asleep. Both phenotypes present in the newborn period. Children with CCHS often have physiologic and anatomic manifestations of a generalized autonomic nervous system dysfunction/dysregulation (ANSD); a subset (16-20%) have altered development of neural crest-derived structures (i.e., Hirschsprung disease) and 5-6% of affected children have tumors of neural crest origin including neuroblastoma, ganglioneuroma, and ganglioneuroblastoma.

Molecular Genetics:

CCHS is inherited in an autosomal dominant manner. PHOX2B maps to chromosome 4p12 and encodes a highly conserved homeobox domain transcription factor. Most individuals with CCHS are heterozygous for de novo repeat expansions in PHOX2B (Paired mesoderm homeobox protein 2B). Approximately 5% of individuals with CCHS have an asymptomatic parent who has somatic mosaicism for a PHOX2B mutation.

Test Methods:

Sequence analysis of the mutation previously identified in a family member will be performed.

Detection Rate:

The analytical sensitivity is close to 100% for point mutations by DNA sequencing.

Related Tests:

Prenatal testing is available to individuals who are confirmed carriers of mutations. Please contact the laboratory director to discuss appropriate testing prior to collecting a prenatal specimen.


Test results with interpretation will be mailed and/or faxed to the referring physician following completion of the test. Additional reports will be provided as requested.


The clinical utility of the assay is in confirming the clinical diagnosis, assessing the risk to other first degree relatives, genotyping at risk family members (such as parents) for already identified mutations and confirming their risk for late onset CCHS. It is also useful in establishing the need for continued clinical surveillance of the patient for the purpose of early detection of tumors.

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