Ordering Recommendation

Recommended test for suspected hereditary neuropathy with liability to pressure palsies (HNPP) and appropriate first-tier test for suspected Charcot-Marie-Tooth type 1 (CMT1) or CMT1A; does not detect sequence variants. Recommended test if there is a known familial PMP22 deletion or duplication previously identified in a family member.

Mnemonic

CMT DD

Methodology

Multiplex Ligation-dependent Probe Amplification

Performed

Varies

Reported

7-14 days

New York DOH Approval Status

Specimens from New York clients will be sent out to a New York DOH approved laboratory, if possible.

Specimen Required

Patient Preparation
Collect

Lavender (EDTA), pink (K2EDTA), or yellow (ACD Solution A or B).

Specimen Preparation

Transport 3 mL whole blood. (Min: 1 mL)

Storage/Transport Temperature

Preferred transport temp: Refrigerated. Also acceptable: Room temperature.

Unacceptable Conditions
Remarks
Stability

Room temperature: 1 week ; Refrigerated: 1 month; Frozen: Unacceptable

Reference Interval

By Report

Interpretive Data

BACKGROUND INFORMATION: Charcot-Marie-Tooth 1A (CMT1A)/ Hereditary Neuropathy with Liability to Pressure Palsies (HNPP), PMP22
Deletion/Duplication
CHARACTERISTICS: Charcot-Marie-Tooth disease, type 1A (CMT1A) is a subtype of CMT1, a hereditary neuropathy characterized by demyelinating progressive distal motor and sensory neuropathy, muscle weakness and atrophy, pes cavus foot deformity, and other findings. CMT1A is caused by duplication of the PMP22 gene. Hereditary neuropathy with liability to pressure palsies (HNPP) is a neurological disorder characterized by repeated focal
pressure neuropathies and peripheral neuropathy caused by deletion of the PMP22 gene.
INCIDENCE: CMT1A: 1/10,000; HNPP: 1/20,000-1/50,000.
INHERITANCE: Autosomal dominant; 10-20 percent of PMP22 duplications are de novo.
CAUSE: CMT1A is caused by a 1.5 Mb duplication at 17p11.2 including the PMP22 gene, while HNPP is caused by the reciprocal deletion of the same region.
CLINICAL SENSITIVITY: 70-80 percent for CMT1; 80 percent for HNPP.
METHODOLOGY: Multiplex ligation-dependent probe amplification (MLPA) of the PMP22 gene.
ANALYTICAL SENSITIVITY AND SPECIFICITY: 99 percent.
LIMITATIONS: Diagnostic errors can occur due to rare sequence variations. Single base pair substitutions, small deletions/duplications, regulatory region mutations, and deep intronic mutations are not detected. The breakpoints of large deletions/duplications are not determined.

This test was developed and its performance characteristics determined by ARUP Laboratories. It has not been cleared or approved by the U.S. Food and Drug Administration. This test was performed in a CLIA-certified laboratory and is intended for clinical purposes.

Counseling and informed consent are recommended for genetic testing. Consent forms are available online.

Compliance Category

Laboratory Developed Test (LDT)

Note

Hotline History

N/A

CPT Codes

81324

Components

Component Test Code* Component Chart Name LOINC
2012161 Charcot-Marie-Tooth/HNPP DelDup Specimen 31208-2
2012162 Charcot-Marie-Tooth/HNPP DelDup Interp 35474-6
* Component test codes cannot be used to order tests. The information provided here is not sufficient for interface builds; for a complete test mix, please click the sidebar link to access the Interface Map.

Aliases

  • Charcot-Marie-Tooth
  • CMT
  • Hereditary Neuropathy
  • Hereditary Neuropathy with liability to Pressure Palsies (HNPP)
Charcot-Marie-Tooth Type 1A (CMT1A)/Hereditary Neuropathy with Liability to Pressure Palsies (HNPP), PMP22 Deletion/Duplication