Charcot-Marie-Tooth Disease Type 1A: PMP22 Deletion/Duplication MLPA

Turnaround Time

2 weeks

CPT Code(s)

81324

Cost

$500

Genes

• Charcot-Marie-Tooth disease

Charcot-Marie-Tooth (CMT) disease is the most common form of inherited peripheral neuropathy, and these conditions have a prevalence of approximately 1 in 3000 individuals. Clinical symptoms include distal muscle weakness with atrophy, loss of deep tendon reflexes, high-arched feet, and loss of sensation. These conditions tend to be progressive, and while most families demonstrate autosomal dominant inheritance, autosomal recessive and X-linked inheritance also occurs. Symptoms and age of onset are variable, but early signs of the disorder include clumsiness, balance problems, and difficulty using the hands to grasp. Hearing loss occurs in some affected individuals, and eventually, some patients require the assistance of a wheelchair. Lifespan and intelligence are not typically affected. Charcot-Marie-Tooth disease is comprised of several types and subtypes. CMT1 is responsible for almost half of all cases of CMT, with CMT2 and CMTX making up an additional 10-15% each. Within the CMT1 type, about 70-80% of cases are due to changes in the PMP22 most often associated with a duplication involving chromosome 17p12. Reciprocal deletions of this region are associated with hereditary neuropathy with liability to pressure palsies, HNPP.

Molecular testing is useful to confirm the diagnosis and to identify the disease causing mutations within a family to allow for carrier testing and prenatal diagnosis.

multiplex ligation-dependent probe amplification (MLPA)

An estimated 30-50% of patients diagnosed with Charcot-Marie-Tooth disease will have a copy number variant in the PMP22 gene. This analysis also detects deletions and duplications in the MPZ and GJB1 genes although sequence variants in these two genes are more common than copy number variants. This test is available individually or as first-tier testing with reflex to the Charcot-Marie-Tooth Hereditary Neuropathy 54-gene panel.

The preferred sample type is 3-5 ml of peripheral blood collected in an EDTA (purple top) tube. Extracted DNA 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.

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.

Prenatal diagnosis is available if the familial mutations are known. Additional fees for cell culture and maternal cell contamination may apply. Maternal cell contamination studies are required for all prenatal molecular tests. Contact the laboratory prior to sending a prenatal specimen.