• Test code: 04740
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit

Invitae Smith-Lemli-Opitz Syndrome Test

Test description

The Invitae Smith-Lemli-Opitz Syndrome Test analyzes DHCR7, a gene associated with Smith-Lemli-Opitz syndrome (SLOS), a severe developmental disorder characterized by prenatal and postnatal growth retardation, distinctive facial features, microcephaly, hypotonia, intellectual disability, and multiple congenital anomalies including cleft palate, 2-3 toe syndactyly and abnormal external genitalia.

Genetic testing of this gene may confirm a diagnosis and help guide treatment and management. Identification of a disease-causing variant can inform recurrence-risk assessment and genetic counseling.

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Primary panel (1 gene)

Smith-Lemli-Optiz syndrome (SLOS) is a congenital developmental disorder caused by a deficiency of the enzyme 7-dehydrocholesterol (7-DHC) reductase causing an abnormality in cholesterol synthesis. SLOS is characterized by prenatal and postnatal growth retardation, distinctive facial features, microcephaly, hypotonia, intellectual disability, and behavioral problems. In addition, cardiac defects, hypospadias in males, 2-3 toe syndactyly, postaxial polydactyly, and other additional features have been reported. Affected individuals exhibit elevated serum concentration of 7-DHC. The clinical spectrum of SLOS varies and patients may present with a mild or severe form of disease.

Greater than 95% of patients with a clinical suspicion of Smith-Lemli Opitz syndrome have pathogenic variants in DHCR7.

Smith-Lemli-Opitz syndrome is inherited in an autosomal recessive manner.

Smith-Lemli-Opitz syndrome is a highly penetrant condition with variable expressivity.

The prevalence of Smith-Lemli-Opitz syndrome is estimated to be 1:20,000 to 1:60,000 newborns.

This test could be considered for patients with 2-3 toe syndactyly, microcephaly, short stature, intellectual disability, cleft palate, postaxial polydactyly, characteristic SLO facial features, and elevated serum concentration of 7-dehydrocholesterol (7-DHC) reductase.

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
DHCR7 NM_001360.2