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Molecular Testing for Smith-Lemli-Opitz Syndrome

Last updated July 9, 2019

Approved by: Krish Tangella MD, MBA, FCAP

Molecular Testing for Smith-Lemli-Opitz 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.


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

  • Gene Mutation Analysis for Smith-Lemli-Opitz Syndrome
  • Molecular Testing for SLOS
  • Test for Molecular Diagnosis of Smith-Lemli-Opitz Syndrome

What is Molecular Testing for Smith-Lemli-Opitz Syndrome? (Background Information)

  • Molecular Testing for Smith-Lemli-Opitz 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
  • Smith-Lemli-Opitz syndrome (SLOS) is an inherited developmental disorder, in which the body is unable to produce enough cholesterol, because of shortage of 7-dehydrocholesterol reductase enzyme, which catalyzes the last step in cholesterol synthesis
  • Since cholesterol is involved in embryonic development, the synthesis of certain hormones and vitamin D3, its deficiency leads to developmental and metabolic disorders
  • The disorder is characterized by multiple congenital anomalies, intellectual abnormalities, and behavioral defects resembling autism spectrum disorders, which can either be mild (type I) or severe (type II)

Smith-Lemli-Opitz syndrome is caused by genetic mutations.

  • Currently, studies indicate that SLOS is caused by mutation(s) in the DHCR7 gene, which codes for the enzyme 7-dehydrocholesterol reductase
  • The disorder is inherited in an autosomal recessive manner
  • Molecular testing may be required for discerning the gene mutation(s) in some cases of SLOS

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 Smith-Lemli-Opitz 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 Smith-Lemli-Opitz Syndrome Test?

Molecular Testing for Smith-Lemli-Opitz Syndrome may be undertaken in the following situations:

  • To assist (and in some cases, confirm) the initial diagnosis of SLOS
  • To check for or ascertain a family history of SLOS
  • 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 Smith-Lemli-Opitz Syndrome?

The type and source and specimen sample requirements will depend on the preference of the individuals and the preference of the testing lab. Thus, it may vary from one individual to another and from one lab to another. Therefore, it is important to contact the testing lab for exact specimen requirements, before initiating the collecting and testing process.

Following is the specimen collection process for Molecular Testing for Smith-Lemli-Opitz Syndrome:

  • Sample on which the test is performed may include:
    • Peripheral blood in individuals showing signs and symptoms suspected of SLOS
    • Bone marrow biopsy specimen
    • For mitochondrial DNA testing, usually a muscle biopsy or a liver biopsy is preferred
    • In case of expectant mothers, prenatal testing through amniotic fluid and chorionic villi sampling
    • Fetal cord blood
    • Fresh tissue from biopsy
    • Fresh tissue from autopsy sample
    • Fresh tissue from fetal demise
    • Buccal brushes: Using the kit that is provided by the testing laboratory, buccal brushes can be used to collect the specimen, by scraping the inner cheek lining (buccal mucosa)
    • Oral rinse specimens
    • Body fluids such as saliva, tears, and semen
    • Dried blood spots: This specimen type is usually requested in situations where the collection and/or shipping of whole blood is not practical
    • In some cases, hair samples (with attached roots), finger nails, and buccal swabs, may be acceptable
    • Formalin-fixed paraffin-embedded solid tumor tissue (FFPE tumor tissue), often referred to as paraffin block of the tumor
    • Products of conception sample from aborted pregnancy
  • Process of obtaining the sample: As outlined by the laboratory testing facility
  • Preparation required: As outlined by the laboratory testing facility

Important Information:

Limitations of specimen while testing for Smith-Lemli-Opitz syndrome

  • For blood specimens: Individuals, who have received platelet transfusions, red blood transfusion, or white blood (leukocyte) transfusion, should wait at least 4 weeks before providing a blood specimen
  • The following specimens may not be acceptable in individuals who have received heterologous bone marrow transplant (in the past):
    • Peripheral blood samples
    • Oral rinse specimens
    • Bone marrow biopsy specimens
  • Testing for Smith-Lemli-Opitz syndrome should not be performed on a transplanted organ/specimen, since the genetic material belongs to the donor and not to the individual being tested
  • Formalin-fixed paraffin-embedded solid tumor tissue: In many cases, FFPE tissue blocks are usually not acceptable. Please contact the testing lab to ascertain, if it is an acceptable sample specimen
  • In some cases, a different source of specimen 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.

Turnaround time for test results

  • Depending on the location of testing, it may take from 2 to 8 weeks from the time of sample collection, to obtain the test results

Sample storage information

•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 Smith-Lemli-Opitz 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 Smith-Lemli-Opitz Syndrome Result?

The significance of Molecular Testing for Smith-Lemli-Opitz Syndrome is explained below:

  • A positive test result helps aid, and in some cases, confirm the diagnosis of SLOS
  • 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 SLOS 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.

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:


Helpful Peer-Reviewed Medical Articles:


Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: April 30, 2017
Last updated: July 9, 2019