Multiple Endocrine Neoplasia Type 2: RET Gene Deletion/Duplication

Condition Description

Multipleendocrine neoplasia type 2 (MEN2) is an autosomal dominant disorder classifiedinto three subtypes: MEN2A, FMTC (familial medullary thyroid carcinoma), and MEN2B. All three subtypes carry a high riskfor development of medullary carcinoma of the thyroid (MTC). MEN2A and MEN2Bcarry an increased risk for pheochromocytoma. MEN2A carries an increased riskfor parathyroid adenoma or hyperplasia. Additional features in MEN2B includemucosal neuromas of the lips and tongue, distinctive facies with enlarged lips,ganglioneuromatosis of the gastrointestinal tract, and an asthenic"Marfanoid" body habitus. The onset of MTC is typically in earlychildhood in MEN2B, early adulthood in MEN2A, and middle age in FMTC.

MEN2A is diagnosed clinically by the occurrence of two or morespecific endocrine tumors [medullary carcinoma of the thyroid (MTC),pheochromocytoma, or parathyroid adenoma/hyperplasia] in a single individual orin close relatives.

Familial medullary thyroid carcinoma (FMTC) is diagnosed in families with four cases of MTC in theabsence of pheochromocytoma or parathyroid adenoma/hyperplasia.

MEN 2B is diagnosed clinically by the presence of mucosalneuromas of the lips and tongue, as well as medullated corneal nerve fibers,distinctive facies with enlarged lips, an asthenic "Marfanoid" bodyhabitus, and MTC.

RET (10q11.2) is the only gene known to be associated with MEN type 2. Molecular genetictesting of the RET gene identifies disease-causing mutations in 95% of individuals with MEN2A and MEN2Band in about 88% of families with FMTC. All MEN2 subtypes are inherited in an autosomal dominant manner. The probability of a de novo gene mutation is 5% or less in index cases with MEN2A and 50% in index cases with MEN2B.

Hirschsprungdisease (HSCR) is a disorder of the enteric plexus of the colon thattypically results in enlargement of the bowel and constipation or obstipationin neonates. Overall, about 20%-40% of all cases of HSCR are caused by germline mutations in the RET and are designated HSCR1. However, most of themutations that cause HSCR1 occur outside of the codons that are mutated inMEN2A

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Genes (1)

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This test is indicated for:

  • Confirmation of a clinical diagnosis of MEN2 in individuals who have tested negative for sequence analysis
  • Individuals at-risk for MEN2 due to family history who have tested negative for sequence analysis


DNA isolated from peripheral blood is hybridized to a CGH array to detect deletions and duplications. The targeted CGH array has overlapping probes which cover the entire genomic region.


Detection is limited to duplications and deletions. The CGH array will not detect point or intronic mutations. Results of molecular analysis must be interpreted in the context of the patient's clinical and/or biochemical phenotype.

Specimen Requirements

Listed below are EGL's preferred sample criteria. For any questions, please call 470.378.2200 and ask to speak with a laboratory genetic counselor (
Submit only 1 of the following specimen types
Whole Blood (EDTA)

EDTA (Purple Top)
Infants and Young Children (<2 years of age): 2-3 ml
Children > 2 years of age to 10 years old: 3-5 ml
Older Children & Adults: 5-10 ml
Autopsy: 2-3 ml unclotted cord or cardiac blood
Collection and Shipping
Ship sample at room temperature for receipt at EGL within 72 hours of collection. Do not freeze.
DNA, Isolated

Isolation using the Perkin Elmer™Chemagen™ Chemagen™ Automated Extraction method or Qiagen™ Puregene kit for DNA extraction is recommended.
Collection and Shipping
Refrigerate until time of shipment in 100 ng/µL in TE buffer. Ship sample at room temperature with overnight delivery.

Special Instructions

Submit copies of diagnostic biochemical test results with the sample, if appropriate. Contact the laboratory if further information is needed.

Sequence analysis is required before deletion/duplication analysis by targeted CGH array. If sequencing is performed outside of EGL Genetics, please submit a copy of the sequencing report with the test requisition.

  • Sequencing analysis of the RET gene is available (VT) and is required before deletion/duplication analysis.
  • Prenataltesting is available to individuals who are confirmed carriers ofmutations. Please contact the laboratory genetic counselor to discussappropriate testing prior to collecting a prenatal specimen.

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