Individuals affected with Congenital Central Hypoventilation Syndrome (CCHS) have adequate ventilation when awake and hypoventilation with normal respiratory rates and shallow breathing during sleep. In severe cases, hypoventilation can also occur while awake. Symptoms usually appear during the newborn period though CCHS is increasingly recognized in older children and adults. Some children with CCHS also show symptoms of a generalized autonomic nervous system dysfunction including Hirschsprung Disease in 20%. Neural crest tumors are found in 6%.

In a few cases, CCHS is inherited in an autosomal dominant pattern, but the majority of cases are de novo. Approximately 92% of affected individuals have an in-frame expansion of a polyalanine repeat in exon 3 of the PHOX2B gene from the normal 20 repeats to 25-33 repeats. The remaining ~8% of patients have other mutations at the end of exon 2 or within exon 3. Mutation type and repeat length generally correlate with disease severity.

The Ambry Test is full gene sequence analyses of the PHOX2B gene. Polyalanine repeat numbers are reported as well as any known or novel non-repeat mutations. Results are reported 10-21 days after testing is initiated.

The following CPT Codes for the Ambry Test reflects Ambry Genetics’ interpretation of CPT coding requirements based on AMA guidelines:

Ambry Test: Congenital Central Hypoventilation Syndrome
83891, 83894, 83898, 83904, 83909, 83912
CPT codes are provided only as a guide to assist you in billing. CPT coding is the sole responsibility of the billing party.

Disclaimer:

This test was developed and its performance characteristics were determined by Ambry Genetics Corporation. The laboratory is regulated under the Clinical Laboratory Improvement Amendments 2003 as qualified to perform nonwaived testing. The Ambry Test: CCHS analyzes the following types of mutations: nucleotide substitutions, small deletions, small insertions (including small repeat expansion), and small indels. It is not intended to analyze the following types of mutations: gross insertions, gross deletions, gross rearrangements, deep intronic variations, and other unknown abnormalities. The pattern of mutation types varies with the gene tested and the Ambry Test detects a high but variable percentage of known and unknown mutants of the classes stated. A negative result from the analysis cannot rule out the possibility that the tested individual carries a rare unexamined mutation or mutation in the undetectable group. The Ambry Test: CCHS is designed and validated to be capable of detecting about 99% of PHOX2B mutations (considering less than 1% to be the other types of mutations). Low-level somatic mosaicism (<10%) for mutations or alanine repeat expansions is not reliably detected by this assay. CCHS is a complex clinical disorder, which in most cases is due to alterations in the PHOX2B gene generally detected by the Ambry Test: CCHS except as noted above. Mutations in other genes or the regions not tested by the Ambry Test: CCHS can also give rise to clinical conditions similar to CCHS. Although molecular tests are highly accurate, rare diagnostic errors may occur. Possible diagnostic errors include sample mix-up, erroneous paternity identification, technical errors, clerical errors, and genotyping errors. Genotyping errors can result from trace contamination of PCR reactions, from maternal cell contamination in fetal samples, from rare genetic variants, which interfere with analysis, or from other sources. This report does not represent medical advice. Any questions, suggestions, or concerns regarding interpretation of results should be forwarded to a genetic counselor, medical geneticist, or physician skilled in interpretation of the relevant medical literature. References are available upon request.