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Test Catalog

Test ID: SLO    
Smith-Lemli-Opitz Screen, Plasma

Useful For Suggests clinical disorders or settings where the test may be helpful

Diagnosis of Smith-Lemli-Opitz syndrome (7-dehydrocholesterol reductase deficiency)

Genetics Test Information Provides information that may help with selection of the correct genetic test or proper submission of the test request

Smith-Lemli-Opitz syndrome (SLO) is a multiple congenital anomaly disorder caused by defective cholesterol biosynthesis due to deficiency of the enzyme 7-dehydrocholesterol reductase.

 

Clinical variability even within families has been noted and severity of SLO ranges from severe to mild.

 

Elevated plasma concentrations of 7-dehydrocholesterol (7-DHC) and 8-dehydrocholesterol (8-DHC) are highly suggestive of a biochemical diagnosis of SLO.

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Cholesterol plays an essential role in many cellular and developmental processes. In addition to its role as a membrane lipid, it is the precursor to numerous molecules that play important roles in cell growth and differentiation, protein glycosylation, and signaling pathways. The biosynthesis of cholesterol and its subsequent conversion to other essential compounds is complex, involving a number of intermediates and enzymes. Disorders that result from a deficiency of these enzymes lead to an accumulation of specific intermediates and inhibit the formation of important biomolecules. Clinical findings common to cholesterol biosynthesis disorders include congenital skeletal malformations, dysmorphic facial features, psychomotor retardation, and failure to thrive.

 

Smith-Lemli-Opitz syndrome (SLO) is an autosomal recessive disorder caused by variants in the DHCR7 gene leading to a deficiency of the 7-dehydrocholesterol reductase enzyme. It is characterized biochemically by markedly increased plasma concentrations of 7-dehydrocholesterol (7-DHC) and 8-dehydrocholesterol (8-DHC) levels. Clinically, features can include microcephaly, growth retardation, developmental delay, dysmorphic facial features, cleft palate, limb abnormalities (especially 2-3 syndactyly of the toes and postaxial polydactyly), and heart and kidney malformations. However, the clinical spectrum ranges from mild to severe with some mildly affected individuals presenting with only 2 to 3 toe syndactyly and mild cognitive impairment. The reported incidence is between 1 in 10,000 and 1 in 60,000, but it may be more prevalent due to underdiagnoses of mildly affected individuals.

 

Other disorders of cholesterol biosynthesis, including desmosterolosis (desmosterol reductase deficiency) and sitosterolemia, may present with similar manifestations. These disorders can be detected biochemically by performing a quantitative profile of plasma sterols (STER / Sterols, Plasma).

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

7-DEHYDROCHOLESTEROL

< or =2.0 mg/L

 

8-DEHYDROCHOLESTEROL

< or = 0.3 mg/L

Interpretation Provides information to assist in interpretation of the test results

Elevated plasma concentrations of 7-dehydrocholesterol (7-DHC) and 8-dehydrocholesterol (8-DHC) are highly suggestive of a biochemical diagnosis of Smith-Lemli-Opitz (SLO).

 

Mild elevations of these cholesterol precursors can be detected in patients with hypercholesterolemia and patients treated with some antipsychotic or antidepressant medications including haloperidol, aripiprazole, and trazodone. However, the 7-DHC to cholesterol ratio is typically elevated only in SLO patients.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

On very rare occasions, 7-dehydrocholesterol is not elevated in patients with Smith-Lemli-Opitz syndrome.

 

Cholesterol screening tests are unreliable for diagnosis for Smith-Lemli-Opitz syndrome.

 

Some antipsychotic or antidepressant medications such as aripiprazole and trazodone cause false elevations in 7-dehydrocholesterol.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Donoghue SE, Pitt JJ, Boneh A, White SM: Smith-Lemli-Opitz syndrome: clinical and biochemical correlates. J Pediatr Endocrinol Metab. 2018;31(4):451-459

2. Nowaczyk MJM: Smith-Lemli-Opitz syndrome. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; November 13, 1998. Updated January 30, 2020. Accessed July 20, 2020. Available at www.ncbi.nlm.nih.gov/books/NBK1143/

3. Hall P, Michels V, Gavrilov D, et al: Aripiprazole and trazodone cause elevations of 7-dehydrocholesterol in the absence of Smith-Lemli-Opitz syndrome. Mol Genet Metab. 2013 Sep-Oct;110(1-2):176-178

4. Genaro-Mattos TC, Tallman KA, Allen LB, et al: Dichlorophenyl piperazines, including a recently-approved atypical antipsychotic, are potent inhibitors of DHCR7, the last enzyme in cholesterol biosynthesis. Toxicol Appl Pharmacol. 2018 Jun 15;349:21-28. doi: 10.1016/j.taap.2018.04.029