Smith–Lemli–Opitz syndrome

Smith-Lemli-Opitz Syndrome 1

Smith–Lemli–Opitz syndrome (SLOS) is a rare autosomal recessive genetic disorder characterized by multiple congenital anomalies and intellectual disability. It is caused by mutations in the DHCR7 gene, which encodes the enzyme 7-dehydrocholesterol reductase. This enzyme is crucial for the final step in the cholesterol biosynthesis pathway.

Signs and Symptoms

Individuals with Smith–Lemli–Opitz syndrome exhibit a wide range of symptoms, which can vary in severity. Common features include:

• Intellectual disability and developmental delays
• Distinctive facial features such as microcephaly, broad nasal bridge, and upturned nostrils
• Hypotonia (low muscle tone)
• Syndactyly (webbing) of the second and third toes
• Polydactyly (extra fingers or toes)
• Cleft palate
• Genital abnormalities in males, such as hypospadias or cryptorchidism
• Feeding difficulties and failure to thrive
• Behavioral problems, including autism spectrum disorder-like behaviors

Genetics

Smith–Lemli–Opitz syndrome is inherited in an autosomal recessive manner. This means that an affected individual must inherit two copies of the mutated DHCR7 gene, one from each parent. Carriers of a single mutated gene typically do not show symptoms of the disorder.

Pathophysiology

The DHCR7 gene mutation leads to a deficiency in the enzyme 7-dehydrocholesterol reductase, which is responsible for converting 7-dehydrocholesterol to cholesterol. As a result, individuals with SLOS have low levels of cholesterol and elevated levels of 7-dehydrocholesterol. Cholesterol is essential for normal embryonic development, cell membrane structure, and the synthesis of steroid hormones and bile acids.

Diagnosis

Diagnosis of Smith–Lemli–Opitz syndrome is based on clinical features and confirmed by biochemical testing showing elevated levels of 7-dehydrocholesterol in the blood. Genetic testing can identify mutations in the DHCR7 gene.

Treatment

There is no cure for Smith–Lemli–Opitz syndrome, and treatment is symptomatic and supportive. Management may include:

• Dietary supplementation with cholesterol
• Physical therapy and occupational therapy to address developmental delays and hypotonia
• Surgical interventions for congenital anomalies such as cleft palate or genital abnormalities
• Behavioral therapy and educational support for intellectual disability and behavioral issues

Prognosis

The prognosis for individuals with Smith–Lemli–Opitz syndrome varies depending on the severity of the condition. Early intervention and supportive care can improve the quality of life for affected individuals.

Related Pages

• Autosomal recessive disorder
• Genetic disorder
• Cholesterol
• Developmental delay
• Intellectual disability
• Congenital anomaly