Smith-Lemli-Opitz syndrome

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ORPHA:818OMIM:270400Q87.1
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1Active trials7Specialists8Treatment centers

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UniteRare data is sourced from FDA.gov, ClinicalTrials.gov, Orphanet, OMIM, and NORD.
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Overview

Smith-Lemli-Opitz syndrome (SLOS), also known as 7-dehydrocholesterol reductase deficiency or RSH syndrome, is an inborn error of cholesterol biosynthesis caused by mutations in the DHCR7 gene. This gene encodes the enzyme 7-dehydrocholesterol reductase, which catalyzes the final step in cholesterol synthesis. Deficiency of this enzyme leads to accumulation of 7-dehydrocholesterol (7-DHC) and reduced levels of cholesterol in the blood and tissues, disrupting normal embryonic and postnatal development. SLOS affects multiple body systems and presents with a wide clinical spectrum ranging from mild to severe. Key features include distinctive facial characteristics (microcephaly, ptosis, small upturned nose, micrognathia), intellectual disability of variable degree, behavioral abnormalities (including features of autism spectrum disorder), growth restriction, and limb anomalies — most characteristically syndactyly of the second and third toes. Congenital malformations may involve the heart, kidneys, brain, ganitalia (particularly ambiguous genitalia or hypospadias in males), and gastrointestinal tract (including pyloric stenosis and Hirschsprung disease). Cleft palate and photosensitivity are also commonly observed. Severely affected individuals may have holoprosencephaly and may not survive the neonatal period. There is no cure for SLOS. The primary treatment approach involves dietary cholesterol supplementation, which can improve growth, behavior, and overall well-being in some patients, although it does not reverse structural malformations or significantly cross the blood-brain barrier. Simvastatin has been investigated as an adjunctive therapy to reduce toxic 7-DHC levels, but evidence for its efficacy remains limited. Management is otherwise supportive and multidisciplinary, addressing feeding difficulties, developmental delays, surgical correction of congenital anomalies, and behavioral interventions. Diagnosis is confirmed by elevated 7-DHC levels in plasma and/or molecular testing of the DHCR7 gene.

Also known as:

Clinical phenotype terms— hover any for plain English:

2-3 toe syndactylyHP:0004691Elevated circulating 7-dehydrocholesterol concentrationHP:0010569Increased nuchal translucencyHP:0010880
Inheritance

Autosomal recessive

Passed on when both parents carry the same gene change; often skips generations

Age of Onset

Neonatal

Begins at or shortly after birth (first 4 weeks)

Orphanet ↗OMIM ↗NORD ↗

FDA & Trial Timeline

1 event
Dec 2008Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)

University of Colorado, Denver — PHASE2

TrialRECRUITING

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Treatments

No FDA-approved treatments are currently listed for Smith-Lemli-Opitz syndrome.

1 clinical trialare actively recruiting — trials can provide access to cutting-edge therapies.

View clinical trials →

Clinical Trials

1 recruitingView all trials with filters →
Phase 21 trial
Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)
Phase 2
Actively Recruiting
PI: Ellen R Elias, MD (University of Colorado, Denver) · Sites: Aurora, Colorado · Age: 065 yrs

Specialists

7 foundView all specialists →
FM
Forbes D Porter, MD
BETHESDA, MD
Specialist
PI on 1 active trial
FM
Forbes D Porter, M.D.
Bethesda, Maryland
Specialist

Rare Disease Specialist

PI on 14 active trials
EM
Ellen R Elias, MD
AURORA, CO
Specialist
PI on 2 active trials
WM
William B Rizzo, MD
ORLANDO, FL
Specialist
PI on 3 active trials1 Smith-Lemli-Opitz syndrome publication
MM
Mira Irons, M.D.
BOSTON, MA
Specialist
PI on 1 active trial
JM
James E. Haddow, M.D.
Specialist
PI on 1 active trial
LS
Laurent Servais
Specialist
PI on 1 active trial28 Smith-Lemli-Opitz syndrome publications

Treatment Centers

8 centers
🏥 NORD

Baylor College of Medicine Rare Disease Center

Baylor College of Medicine

📍 Houston, TX

🏥 NORD

Stanford Medicine Rare Disease Center

Stanford Medicine

📍 Stanford, CA

🔬 UDN

NIH Clinical Center Undiagnosed Diseases Program

National Institutes of Health

📍 Bethesda, MD

🔬 UDN

UCLA UDN Clinical Site

UCLA Health

📍 Los Angeles, CA

🔬 UDN

Baylor College of Medicine UDN Clinical Site

Baylor College of Medicine

📍 Houston, TX

🔬 UDN

Harvard/MGH UDN Clinical Site

Massachusetts General Hospital

📍 Boston, MA

🏥 NORD

Mayo Clinic Center for Individualized Medicine

Mayo Clinic

📍 Rochester, MN

👤 Mayo Clinic Center for Individualized Medicine

🏥 NORD

UCLA Rare Disease Day Program

UCLA Health

📍 Los Angeles, CA

Travel Grants

No travel grants are currently matched to Smith-Lemli-Opitz syndrome.

Search all travel grants →NORD Financial Assistance ↗

Community

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Caregiver Resources

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Common questions about Smith-Lemli-Opitz syndrome

What is Smith-Lemli-Opitz syndrome?

Smith-Lemli-Opitz syndrome (SLOS), also known as 7-dehydrocholesterol reductase deficiency or RSH syndrome, is an inborn error of cholesterol biosynthesis caused by mutations in the DHCR7 gene. This gene encodes the enzyme 7-dehydrocholesterol reductase, which catalyzes the final step in cholesterol synthesis. Deficiency of this enzyme leads to accumulation of 7-dehydrocholesterol (7-DHC) and reduced levels of cholesterol in the blood and tissues, disrupting normal embryonic and postnatal development. SLOS affects multiple body systems and presents with a wide clinical spectrum ranging from m

How is Smith-Lemli-Opitz syndrome inherited?

Smith-Lemli-Opitz syndrome follows a autosomal recessive inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.

At what age does Smith-Lemli-Opitz syndrome typically begin?

Typical onset of Smith-Lemli-Opitz syndrome is neonatal. Age of onset can vary across affected individuals.

Are there clinical trials for Smith-Lemli-Opitz syndrome?

Yes — 1 recruiting clinical trial is currently listed for Smith-Lemli-Opitz syndrome on UniteRare. See the clinical trials section on this page for phase, sponsor, and site details sourced from ClinicalTrials.gov.

Which specialists treat Smith-Lemli-Opitz syndrome?

7 specialists and care centers treating Smith-Lemli-Opitz syndrome are listed on UniteRare, sourced from ClinicalTrials.gov principal investigators, published research, and the NPPES NPI registry.