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PubMed This is a summary of 18 peer-reviewed journal articles Updated
Medical Genetics

Understanding Smith-Lemli-Opitz Syndrome: The First Steps

At a Glance

Smith-Lemli-Opitz Syndrome (SLOS) is a rare genetic disorder caused by a DHCR7 gene mutation that impairs cholesterol production and causes a toxic buildup of 7-DHC. While symptoms vary widely, care focuses on cholesterol supplementation and multidisciplinary support to improve quality of life.

Receiving a diagnosis of Smith-Lemli-Opitz Syndrome (SLOS) can be overwhelming and frightening. It is important to know that while this condition is rare, there is a dedicated community of researchers and clinicians working to understand and manage it. This page is designed to help you stabilize after the initial news by explaining the biological facts of the condition and providing a realistic outlook for you or your child’s journey.

Understanding the Biological Mechanism

SLOS is an autosomal recessive genetic disorder. This means a person must inherit one changed (mutated) copy of the DHCR7 gene from each parent to have the condition [1]. For parents who carry this mutation, there is a 25% (1 in 4) chance with each pregnancy of having a child with SLOS. This gene is responsible for providing instructions to make an enzyme that performs the final step in creating cholesterol [2].

In individuals with SLOS, this enzyme does not work correctly. This leads to two primary issues in the body:

  1. Cholesterol Deficiency: The body cannot produce enough cholesterol, which is essential for building cell membranes, producing hormones, and ensuring proper brain development [3][4].
  2. 7-DHC Buildup: A precursor molecule called 7-dehydrocholesterol (7-DHC)—which should have been turned into cholesterol—instead builds up to high levels in the blood and tissues [1][2].

Why Cholesterol Matters

While we often hear about cholesterol in the context of heart health, it is actually a vital building block. It is critical for Sonic Hedgehog (Shh) signaling, a biological pathway that tells cells how to organize themselves into organs and limbs during early development [4][5]. When cholesterol is low and 7-DHC is high, this signaling can be disrupted, leading to the physical and developmental features associated with SLOS.

Facts to Help You Move Forward

It is easy to feel lost in medical data, but these stabilizing facts can help you find your footing:

  • The Spectrum is Wide: SLOS is not a “one size fits all” condition. The symptoms range from very mild to more severe. Some individuals with milder forms of SLOS are diagnosed as adults, achieve near-normal cognitive development, and lead stable lives [6][7].
  • Survival into Adulthood: While there are serious health risks associated with SLOS, many individuals successfully grow into adulthood [8]. Medical management has improved significantly over the years, and a multidisciplinary care team can help address specific needs [9].
  • Proactive Management Exists: While there is currently no “cure,” doctors use several strategies to support individuals with SLOS. This often includes cholesterol supplementation (dietary or medical grade) to increase cholesterol levels and potentially lower the toxic buildup of 7-DHC [10][11].

Why You Might Not Have Heard of SLOS

SLOS is estimated to occur in roughly 1 in 20,000 to 1 in 60,000 births, particularly in populations of North American and European descent [12]. However, researchers believe it is frequently underdiagnosed [13].

Because the symptoms can be mild—sometimes appearing only as minor learning delays or small physical signs like 2,3 toe syndactyly (webbing between the second and third toes)—doctors who aren’t familiar with the syndrome may miss the diagnosis [14][7]. A formal diagnosis is a powerful tool because it allows you to stop wondering “why” and start building a targeted care plan.

Next Steps in Care

Standard clinical management focuses on an integrated, multidisciplinary approach [9]. This typically involves:

  • Nutritional Support: Monitoring growth and introducing cholesterol-rich diets or supplements [15].
  • Monitoring Health: Routine checks for potential issues with the heart, kidneys, vision, and hearing [16][17].
  • Developmental Support: Early intervention services, including physical, occupational, and speech therapy, to help reach full potential [18].

Common questions in this guide

How do you get Smith-Lemli-Opitz Syndrome?
SLOS is an autosomal recessive genetic disorder. This means a person must inherit one mutated copy of the DHCR7 gene from each parent to develop the condition. Parents who carry the mutation have a 25 percent chance with each pregnancy of having a child with SLOS.
What causes the symptoms of SLOS?
Symptoms are caused by an enzyme defect that prevents the body from producing enough cholesterol while causing a toxic buildup of a precursor molecule called 7-DHC. Because cholesterol is vital for cell signaling and brain development, this imbalance affects how the body and organs develop.
Is there a cure for Smith-Lemli-Opitz Syndrome?
While there is no cure, SLOS can be managed proactively. Doctors often recommend dietary or medical-grade cholesterol supplementation to improve cholesterol levels and help reduce the toxic buildup of 7-DHC in the body.
What kind of doctors manage SLOS care?
Because SLOS can affect many different body systems, care involves a multidisciplinary team. This often includes a medical geneticist, a specialized metabolic dietitian, and therapists who provide physical, occupational, and speech therapy support.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.What are the current serum cholesterol and 7-dehydrocholesterol (7-DHC) levels?
  2. 2.Does our local hospital have a specialized metabolic dietitian familiar with cholesterol supplementation?
  3. 3.What screening schedule do you recommend for monitoring potential internal complications, such as kidney, heart, or vision issues?
  4. 4.Can you refer us to a medical genetics team to discuss the specific DHCR7 mutations and what they might mean?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (18)
  1. 1

    Smith-Lemli-Opitz syndrome: A pathophysiological manifestation of the Bloch hypothesis.

    Chattopadhyay A, Sharma A

    Frontiers in molecular biosciences 2023; (10()):1120373 doi:10.3389/fmolb.2023.1120373.

    PMID: 36714259
  2. 2

    The role of cholesterol biosynthesis and metabolism causing medical complexity in patients with Smith-Lemli-Opitz Syndrome (SLOS).

    Elias ER

    The Journal of steroid biochemistry and molecular biology 2025; (254()):106822 doi:10.1016/j.jsbmb.2025.106822.

    PMID: 40609800
  3. 3

    Temporal changes in the brain lipidome during neurodevelopment of Smith-Lemli-Opitz syndrome mice.

    Li A, Hines KM, Ross DH, et al.

    The Analyst 2022; (147(8)):1611-1621 doi:10.1039/d2an00137c.

    PMID: 35293916
  4. 4

    Reduced cholesterol levels impair Smoothened activation in Smith-Lemli-Opitz syndrome.

    Blassberg R, Macrae JI, Briscoe J, Jacob J

    Human molecular genetics 2016; (25(4)):693-705 doi:10.1093/hmg/ddv507.

    PMID: 26685159
  5. 5

    Endogenous B-ring oxysterols inhibit the Hedgehog component Smoothened in a manner distinct from cyclopamine or side-chain oxysterols.

    Sever N, Mann RK, Xu L, et al.

    Proceedings of the National Academy of Sciences of the United States of America 2016; (113(21)) doi:10.1073/pnas.1604984113.

    PMID: 27162362
  6. 6

    Smith-Lemli-Opitz Syndrome with Biallelic c.1295A>G (p.Tyr432Cys) Variant in the DHCR7 Gene in a 73-Year-Old Woman: Report of the Oldest Patient.

    Yılmaz M, Bebek O, Turkyilmaz A

    Molecular syndromology 2024; (15(4)):317-323 doi:10.1159/000536343.

    PMID: 39119449
  7. 7

    Familial DHCR7 genotype presenting as a very mild form of Smith-Lemli-Opitz syndrome and lethal holoprosencephaly.

    Temple SEL, Sachdev R, Ellaway C

    JIMD reports 2020; (56(1)):3-8 doi:10.1002/jmd2.12155.

    PMID: 33204589
  8. 8

    Assessing Postnatal Mortality in Smith-Lemli-Opitz Syndrome.

    Selvaraman A, Rahhal S, Bianconi S, et al.

    American journal of medical genetics. Part A 2025; (197(2)):e63875 doi:10.1002/ajmg.a.63875.

    PMID: 39271956
  9. 9

    Smith-Lemli-Opitz syndrome: Clinical, biochemical, and genetic insights with emerging treatment opportunities.

    Kritzer A, Dutta R, Pramparo T, et al.

    Genetics in medicine : official journal of the American College of Medical Genetics 2025; (27(7)):101450 doi:10.1016/j.gim.2025.101450.

    PMID: 40314187
  10. 10

    Cholic acid increases plasma cholesterol in Smith-Lemli-Opitz syndrome: A pilot study.

    Elias ER, Orth LE, Li A, et al.

    Molecular genetics and metabolism reports 2024; (38()):101030 doi:10.1016/j.ymgmr.2023.101030.

    PMID: 38077958
  11. 11

    The Smith-Lemli-Opitz syndrome and dentofacial anomalies diagnostic: Case reports and literature review.

    Rojare C, Opdenakker Y, Laborde A, et al.

    International orthodontics 2019; (17(2)):375-383 doi:10.1016/j.ortho.2019.03.020.

    PMID: 31005410
  12. 12

    Smith-Lemli-Opitz syndrome - Fetal phenotypes with special reference to the syndrome-specific internal malformation pattern.

    Schoner K, Witsch-Baumgartner M, Behunova J, et al.

    Birth defects research 2020; (112(2)):175-185 doi:10.1002/bdr2.1620.

    PMID: 31840946
  13. 13

    Smith-Lemli-Opitz syndrome carrier frequency and estimates of in utero mortality rates.

    Lazarin GA, Haque IS, Evans EA, Goldberg JD

    Prenatal diagnosis 2017; (37(4)):350-355 doi:10.1002/pd.5018.

    PMID: 28166604
  14. 14

    Keeping you on your toes: Smith-Lemli-Opitz Syndrome is an easily missed cause of developmental delays.

    Coupe S, Hertzog A, Foran C, et al.

    Clinical case reports 2023; (11(2)):e6920 doi:10.1002/ccr3.6920.

    PMID: 36814711
  15. 15

    Biochemical and Clinical Effects of Vitamin E Supplementation in Hungarian Smith-Lemli-Opitz Syndrome Patients.

    Koczok K, Horváth L, Korade Z, et al.

    Biomolecules 2021; (11(8)) doi:10.3390/biom11081228.

    PMID: 34439893
  16. 16

    Smith-Lemli-Opitz Syndrome: Oral Characteristics and Risk Factors for Caries Development.

    Olczak-Kowalczyk D, Witt-Porczyk A, Piekoszewska-Ziętek P, Krajewska-Walasek M

    Biomedicines 2025; (13(3)) doi:10.3390/biomedicines13030574.

    PMID: 40149551
  17. 17

    A Case of Smith-Lemli-Opitz Syndrome Diagnosed with Hypertrophic Pyloric Stenosis.

    Eren EE, Bilgin N, Urganci N, Kose G

    Sisli Etfal Hastanesi tip bulteni 2021; (55(2)):268-271 doi:10.14744/SEMB.2020.34651.

    PMID: 34349606
  18. 18

    Smith-Lemli-Opitz Syndrome (SLOS)-Case Description and the Impact of Therapeutic Interventions on Psychomotor Development.

    Kozera N, Śmigiel R, Rozensztrauch A

    Journal of clinical medicine 2025; (14(23)) doi:10.3390/jcm14238569.

    PMID: 41375871

This page provides educational information about Smith-Lemli-Opitz Syndrome. Always consult a geneticist or specialized metabolic care team for personalized medical advice and treatment.

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