What is Smith-Lemli-Opitz syndrome?

From the Guidelines

Smith-Lemli-Opitz syndrome (SLOS) patients should be treated with cholesterol supplementation, usually 50-300 mg/kg/day, to improve growth and behavior, and simvastatin may be added to reduce toxic precursors, as the primary goal is to minimize morbidity and mortality while maximizing quality of life. The clinical spectrum and severity of presentation in SLOS vary, with patients presenting with prenatal and postnatal growth restriction, moderate-to-severe intellectual disability, distinctive facial features, cardiac defects, underdeveloped external genitalia in males, and 2–3 syndactyly of the toes 1. Laboratory findings are significant for elevated 7-dehydrocholesterol and usually low serum total cholesterol and LDL-C, albeit many patients will have normal cholesterol and LDL-C levels 1.

The pathophysiology of SLOS is unclear, but it is thought to be secondary to decreased cholesterol synthesis, lower cholesterol levels, or toxic accumulation of the pro-drome 7-DHC 1. Management of SLOS requires a multidisciplinary approach, including developmental specialists, cardiologists, gastroenterologists, and other specialists based on individual symptoms. Early intervention with physical, occupational, and speech therapy is crucial for maximizing developmental potential. Genetic counseling is recommended for affected families, as SLOS follows an autosomal recessive inheritance pattern 1.

Key aspects of SLOS management include:

• Cholesterol supplementation to improve growth and behavior
• Simvastatin to reduce toxic precursors
• Multidisciplinary approach to address individual symptoms
• Early intervention with physical, occupational, and speech therapy
• Genetic counseling for affected families It is essential to prioritize the patient's quality of life, minimizing morbidity and mortality, while managing the complex symptoms and anomalies associated with SLOS 1.

From the Research

Overview of Smith-Lemli-Opitz Syndrome

• Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive genetic condition characterized by a broad phenotype resulting from a deficiency of the final enzyme of the cholesterol synthesis pathway 2.
• This defect causes low or low-normal plasma cholesterol levels and increased 7- and 8-dehydrocholesterol (DHC) levels 2, 3.

Biochemical Features

• Cholesterol synthesis in SLOS subjects is significantly reduced compared to control subjects 3.
• The synthesis of 7-DHC and other cholesterol precursors is profoundly increased in SLOS subjects 3.
• Bile acid synthesis in SLOS subjects is normal and does not differ significantly from control subjects 3, 4.

Clinical Features

• SLOS is characterized by a range of malformations, including branchial arch abnormalities, immune dysfunction, and hypocalcemia 5, 6.
• Patients with SLOS often have intellectual disability and may have electrolyte abnormalities, necrotizing enterocolitis, and sepsis-like episodes 6.
• The severity of the clinical features of SLOS is correlated with the level of cholesterol, with patients having lower cholesterol levels tend to have more severe features 6.

Treatment and Management

• Various therapies for SLOS have been proposed, including dietary cholesterol therapy, statin treatment, bile acid supplementation, medical therapies, and surgical interventions 2.
• Early diagnosis and intervention to correct the biochemical consequences of SLOS may decrease mortality and improve long-term outcome in these patients 6.