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Molecular Testing for Myhre Syndrome

Last updated April 7, 2017


What are other Names for this Test? (Equivalent terms)

  • Gene Mutation Analysis for Myhre Syndrome
  • Test for Molecular Diagnosis of Myhre Syndrome

What is Molecular Testing for Myhre Syndrome? (Background Information)

  • Molecular Testing for Myhre Syndrome is a genetic test that is helpful in aiding a diagnosis of the disorder. The lab test results may also be subsequently useful in taking appropriate treatment decisions
  • Myhre syndrome is an extremely uncommon genetic disorder characterized by several physical abnormalities and often accompanied by impaired intellectual development. Many cases are reported in males
  • Symptoms may include growth deficiency, skeletal abnormalities, certain characteristic facial features, stiff joints, abnormalities in formation and function of organs, and intellectual disability

The cause of Myhre syndrome may be due to genetic mutations. In majority of cases, spontaneous mutation(s) in the SMAD4 gene is observed.

  • The SMAD4 gene is an integral part of an important signaling pathway, which modulates several aspects of growth and development
  • A defective SMAD4 protein interferes with the proper functioning of this pathway, leading to the characteristic symptoms of the disorder
  • Molecular testing may be required for discerning the gene mutation(s) in some cases of Myhre Syndrome

A positive or negative test result should always be interpreted in the context of the individual’s overall signs and symptoms.

Molecular testing, in general, can be performed using a variety of methods. Some of these methods include:

  • In situ hybridization techniques, such as fluorescence in situ hybridization (FISH)
  • Immunohistochemistry (IHC)
  • Next-generation sequencing (NGS)
  • Polymerase chain reaction (PCR)
  • Comparative genomic hybridization (CGH)
  • Karyotyping including spectral karyotyping
  • mRNA analysis
  • Tissue microarrays (TMAs)
  • Southern blot test
  • Northern blot test
  • Western blot test
  • Eastern blot test

The methodology used for Myhre syndrome may vary from one laboratory to another.

Note: Molecular testing has limitations depending on the method being used, and genetic mutational abnormalities being tested. This can affect the results on a case-by-case basis. Consultation with your healthcare provider will help in determining the right test and right molecular method, based on individual circumstances.

What are the Clinical Indications for performing the Molecular Testing for Myhre Syndrome Test?

Molecular Testing for Myhre Syndrome may be undertaken in the following situations: 

  • To assist (and in some cases, confirm) the initial diagnosis of Myhre syndrome
  • To check for or ascertain a family history of the disorder
  • To distinguish other conditions that have similar features (signs and symptoms)
  • To help determine treatment options

How is the Specimen Collected for Molecular Testing for Myhre Syndrome?

Following is the specimen collection process for Molecular Testing for Myhre Syndrome:

The specimen sample requirements may vary from lab to lab. Hence, it is important to contact the testing lab for exact specimen requirements, before initiating the testing process.

  • Sample on which the test is performed may include:
    • Peripheral blood in individuals showing signs and symptoms suspected of Myhre syndrome
    • In case of expectant mothers, prenatal testing through amniotic fluid and chorionic villi sampling
    • Tissue from biopsy
    • Unstained tissue slides 
  • Process of obtaining the sample: As outlined by the laboratory testing facility
  • Preparation required: As outlined by the laboratory testing facility

Note:

  • In some cases, a different source of specimen (such as peripheral blood, bone marrow biopsy specimen, or other body fluids) may be acceptable to the laboratory performing the test
  • Occasionally, additional samples may be required to either repeat the test or to perform follow-up testing
  • Depending on the location of testing, it may take up to 2 weeks’ turnaround time, to obtain the test results
  • Many hospitals preserve the paraffin blocks for at least 7 years. In general, older paraffin blocks (over 5 years) may affect the detection of specific mutations, due to degradation of the tissue specimen over time

Cost of Molecular Testing for Myhre Syndrome:

  • The cost of the test procedure depends on a variety of factors, such as the type of your health insurance, annual deductibles, co-pay requirements, whether your healthcare provider/facility is in-network or out-of-network of your insurance company
  • In many cases, an estimate may be provided before the test is conducted. The final amount may depend upon the findings during the test procedure and post-operative care, if required

What is the Significance of the Molecular Testing for Myhre Syndrome Result?

The significance of Molecular Testing for Myhre Syndrome is explained below:

  • A positive test result helps aid, and in some cases, confirm the diagnosis of Myhre syndrome
  • The test results can help in the following manner:
    • Exclude other conditions presenting with similar signs and symptoms
    • Determine the prognosis of the patient
    • In management of the condition following birth of the child, if the condition is diagnosed prenatally
    • In making treatment decisions
  • Individuals showing a positive test result during pregnancy may benefit from genetic counseling
  • If a causative gene mutation for Myhre syndrome is identified in a family, then genetic counseling may be recommended to help assess the risk, before planning for a child

The laboratory test results are NOT to be interpreted as results of a "stand-alone" test. The test results have to be interpreted after correlating with suitable clinical findings and additional supplemental tests/information. Your healthcare providers will explain the meaning of your tests results, based on the overall clinical scenario.

Additional and Relevant Useful Information:

  • Many laboratories may not have the capability to perform this test. Only highly-specialized labs with advanced facilities and testing procedures may offer this test
  • Ongoing research may discover additional gene mutations for this condition. This may further contribute towards diagnosis and treatment. Please consult with your healthcare provider for updates

Certain medications may influence the outcome of the test. Hence, it is important to inform your healthcare provider of the complete list of medications (including any herbal supplements) you are currently taking. This will help the healthcare provider interpret your test results more accurately and avoid any possibility of a misdiagnosis.

What are some Useful Resources for Additional Information?

Please visit our Laboratory Procedures Center for more physician-approved health information:

http://www.dovemed.com/common-procedures/procedures-laboratory/

References and Information Sources used for the Article:

https://ghr.nlm.nih.gov/primer/testing/genetictesting (accessed on 03/21/2017) 

https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5806a1.htm (accessed on 03/21/2017)

http://www.nature.com/gim/journal/v10/n5/full/gim200852a.html (accessed on 03/21/2017)

http://pediatrics.aappublications.org/content/106/6/1494 (accessed on 03/21/2017)

https://media.bcm.edu/documents/2014/84/smad4-mutation-analysis.pdf (accessed on 03/21/2017)

https://www.ncbi.nlm.nih.gov/gtr/conditions/C0796081/ (accessed on 03/21/2017)

Helpful Peer-Reviewed Medical Articles:

Carrano, A. V., et al. Measurement and purification of human chromosomes by flow cytometry and sorting. Proceedings of the National Academy of Sciences 76, 1382–1384 (1979)

Drets, M. E., & Shaw, M. W. Specific banding patterns of human chromosomes. Proceedings of the National Academy of Sciences 68, 2073–2077 (1971)

Druker, B. J. Perspectives on the development of a molecularly targeted agent. Cancer Cell 1, 31–36 (2002)

Parra, I., & Windle, B. High resolution visual mapping of stretched DNA by fluorescent hybridization. Nature Genetics 5, 17–21 (1993) doi:10.1038/ng0993-17

Pinkel, D., et al. High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays. Nature Genetics 20, 207–211 (1998) doi:10.1038/2524

Speicher, M. R., et al. Karyotyping human chromosomes by combinatorial multi-fluor FISH. Nature Genetics 12, 368–375 (1996) doi:10.1038/ng0496-368

Burglen, L., Heron, D., Moerman, A., Dieux-Coeslier, A., Bourguignon, J. P., Bachy, A., ... & Verloes, A. (2003). Myhre syndrome: new reports, review, and differential diagnosis. Journal of medical genetics, 40(7), 546-551.

Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: April 7, 2017
Last updated: April 7, 2017