Collect whole blood in a purple top (EDTA) tube.
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.
Heparinized specimens, severely hemolyzed specimens, frozen, clotted or possibly commingled specimens, blood in non-sterile or leaky containers, mislabeled or inappropriately labeled specimens.
Do not heat, freeze or centrifuge blood before shipment. Refrigerate sample until shipment.
Mon - Fri 9:00am to 4:00pm
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.
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.
We offer DNA sequence analysis of the entire coding region of the PHOX2B gene. PCR amplification and sequencing is performed on all coding exons including splice junctions. The patient’s gene sequence is then compared to a reference sequence. Sequence variants are classified as mutations, variants of unknown significance or benign variants unrelated to disease. Variants of unknown significance may warrant further studies in the patient and other family members. Large deletions, mutations in promoters, deep intronic regions and other regulatory regions will not be identified with this assay.
Mutations in the PHOX2B gene have been identified in >92% of patients with a clinical diagnosis of CCHS.
Known mutation analysis is available to family members for previously identified mutations.
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.
Whole blood in EDTA purple top tubes is the preferred sample. High molecular weight genomic DNA, cheek epithelial cells, or other samples containing DNA may be acceptable. Contact the laboratory for specific instructions regarding such samples before sending the sample.