Is Smith-Lemli-Opitz Syndrome hereditary?

TL;DR: Smith-Lemli-Opitz syndrome is a hereditary genetic condition inherited in an autosomal recessive pattern, meaning an affected individual must inherit two copies of a mutated DHCR7 gene—one from each parent. Because both parents are typically asymptomatic carriers, each subsequent pregnancy for carrier couples carries a 25% risk of having a child with the syndrome.

Is Smith-Lemli-Opitz syndrome hereditary?

Smith-Lemli-Opitz syndrome is a strictly hereditary, autosomal recessive metabolic disorder. It is not caused by environmental factors, nor is it a multifactorial condition; it is caused specifically by mutations in the DHCR7 gene, which provides instructions for making the enzyme 7-dehydrocholesterol reductase. This enzyme is the final step in the body's cholesterol production pathway. Because it is autosomal recessive, a child only develops Smith-Lemli-Opitz syndrome if they inherit a pathogenic variant from both biological parents. A person who carries only one mutated copy is considered a "carrier" and typically does not show symptoms of the condition.

What is the risk of recurrence for parents?

When both parents are identified as carriers of a DHCR7 gene mutation, the mathematical risk for each pregnancy is as follows:

• 25% chance that the child will have Smith-Lemli-Opitz syndrome (inheriting two mutated copies).


• 50% chance that the child will be an asymptomatic carrier (inheriting one mutated copy).


• 25% chance that the child will be unaffected and not a carrier (inheriting two normal copies).

It is important to note that de novo (spontaneous) mutations in Smith-Lemli-Opitz syndrome are extremely rare. In the vast majority of clinical cases, both parents are confirmed to be carriers, even if they have no family history of the condition.

How is genetic testing and counseling utilized?

Genetic testing for Smith-Lemli-Opitz syndrome is highly accurate and involves molecular genetic testing of the DHCR7 gene. If a child is diagnosed with the syndrome, clinical geneticists strongly recommend that parents undergo carrier testing to confirm their status and determine the specific familial mutations. For families planning future pregnancies, genetic counseling is essential to discuss reproductive options, which may include:

• Prenatal diagnosis: Using chorionic villus sampling (CVS) or amniocentesis to test the fetus during pregnancy.


• Preimplantation Genetic Testing (PGT): Utilizing IVF to screen embryos for the DHCR7 mutations before implantation.


• Carrier screening: Testing extended family members who may also be at risk of being carriers.

Why connect with the community?

Navigating a rare diagnosis like Smith-Lemli-Opitz syndrome can feel isolating. At DiseaseMaps.org, 61 people with Smith-Lemli-Opitz syndrome have joined our community to share their personal experiences, management strategies, and emotional support. Connecting with others who understand the clinical and daily complexities of this syndrome can provide invaluable insights that go beyond medical literature.

Next steps

• Consult with a board-certified clinical geneticist to discuss family testing and recurrence risks.


• Request a referral to a metabolic specialist to manage the specific cholesterol-deficiency needs associated with Smith-Lemli-Opitz syndrome.


• Join the DiseaseMaps.org community to share experiences and connect with other families affected by this condition.


• Review your family history and discuss with a genetic counselor whether extended family members should pursue carrier screening.

Medical disclaimer: This information is for educational purposes and should not replace professional medical advice, diagnosis, or treatment; always consult with a qualified healthcare provider regarding your specific medical condition.

References

• NIH Genetic and Rare Diseases (GARD) Information Center: Smith-Lemli-Opitz syndrome.


• Orphanet: Smith-Lemli-Opitz syndrome (ORPHA:817).


• Online Mendelian Inheritance in Man (OMIM): 7-DEHYDROCHOLESTEROL REDUCTASE; DHCR7.


• Smith-Lemli-Opitz Syndrome Foundation: Patient and family support resources.