Central Hypoventilation Syndrome: PHOX2B Polyalanine Repeat

Test Information

Turnaround Time

7 days

CPT Code(s)





  • PHOX2B

Clinical Information

Central hypoventilation syndrome is an autosomal dominant disorder that is characterized by shallow breathing with occasional apnea. Age of onset is typically in the newborn period, and the features are due to autonomic dysregulation. Other symptoms may include cardiac arrhythmias, temperature instability, profuse sweating, and diminished reactivity of the pupils. Hirschsprung disease occurs in up to 20% of affected individuals with severe constipation in a significant number of additional patients. An increased risk for neural crest tumors such as neuroblastoma, ganglioneuroma, and ganglioneuroblastoma is present with a higher risk among individuals with non-polyalanine expansions in PHOX2B. Ventilatory support is required throughout life although some individuals will only require support during sleep.


Fragment analysis to detect expansion followed by Sanger sequencing when indicated.


Polyalanine repeat analysis can detect approximately 90-92% of pathogenic variants within PHOX2B. There are three types of PHOX2B pathogenic variants: polyalanine repeat expansion mutations, non-polyalanine repeat expansions (typically small out-of-frame deletions or duplications), and whole-gene or exon 3 deletions. This analysis can detect polyalanine repeat expansions and frameshift non-polyalanine repeat expansions within the second polyalanine repeat region. Sequencing may be needed to identify other non-polyalanine repeat expansions. Additionally, deletion/duplication analysis may be needed to identify whole-gene or exon 3 deletions.

Specimen Requirements

The preferred sample type is 3-5 ml of peripheral blood collected in an EDTA (purple top) tube. Extracted DNA, dried blood spots, and saliva are also accepted for this test. Saliva samples must be submitted in an approved saliva kit. Contact the lab to receive a saliva kit or to have one sent to your patient.

Transport Instructions

The specimen should be kept at room temperature and delivered via overnight shipping. If shipment is delayed by one or two days, the specimen should be refrigerated and shipped at room temperature. Do not freeze the specimen. Samples collected on Friday can be safely designated for Monday delivery.

Have Questions? Need Support?

Call our laboratory at 1-800-473-9411 or contact one of our Laboratory Genetic Counselors for assistance.
Robin Fletcher, MS, CGC
Falecia Thomas, MS, CGC
Alex Finley, MS, CGC

Meet Reggie Roper

Reggie has been part of the GGC family for over 18 years. He has short stature, webbing of his hands, pulmonary stenosis, seizures and hydrocephalus along with developmental delay. He carried an initial diagnosis of cardiofaciocutaneous (CFC) syndrome; however, as genetic testing advanced, GGC made the diagnosis of Noon...

In The News