Smith-lemli-opitz syndrome

Smith-Lemli-Opitz syndrome 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:

• Microcephaly (small head size)
• Intellectual disability
• Distinctive facial features such as a broad nasal bridge, upturned nose, and micrognathia (small jaw)
• Syndactyly (webbing) of the second and third toes
• Polydactyly (extra fingers or toes)
• Hypotonia (low muscle tone)
• Feeding difficulties
• Behavioral problems such as autism spectrum disorder and self-injurious behavior

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.

Diagnosis

Diagnosis of Smith-Lemli-Opitz syndrome is based on clinical features and can be confirmed by biochemical testing showing elevated levels of 7-dehydrocholesterol and reduced levels of cholesterol 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 primarily supportive and symptomatic. Management strategies may include:

• Dietary supplementation with cholesterol
• Physical therapy and occupational therapy
• Speech therapy
• Behavioral interventions and support for intellectual disability
• Surgical correction of congenital anomalies

Prognosis

The prognosis for individuals with Smith-Lemli-Opitz syndrome varies widely depending on the severity of the condition. Some individuals may have mild symptoms and lead relatively normal lives, while others may have severe disabilities and require lifelong care.

History

Smith-Lemli-Opitz syndrome was first described in 1964 by pediatricians David Smith, Luc Lemli, and John Opitz. The genetic basis of the disorder was identified in the 1990s.

Related Pages

• Genetic disorder
• Autosomal recessive
• Cholesterol
• Intellectual disability
• Microcephaly
• Syndactyly
• Polydactyly
• Hypotonia
• Autism spectrum disorder