Smith-Lemli-Opitz syndrome: clinical and biochemical correlates

Area of Science:

• Biochemistry
• Genetics
• Developmental Biology

Background:

• Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder.
• It is caused by mutations in the DHCR7 gene, leading to impaired cholesterol biosynthesis.
• Cholesterol plays a critical role in morphogenesis and steroidogenesis.

Purpose of the Study:

• To investigate the biochemical and clinical manifestations of SLOS.
• To correlate cholesterol levels with disease severity and patient outcomes.

Main Methods:

• Retrospective review of medical records for 18 patients (including fetuses) with confirmed SLOS.
• Documentation of clinical and biochemical features.

Main Results:

• Seven patients presented with branchial arch abnormalities, micrognathia, immune dysfunction, and hypocalcemia.
• Four patients with cholesterol levels ≤0.35 mmol/L died, exhibiting severe electrolyte abnormalities, necrotizing enterocolitis, sepsis-like episodes, and midline defects.
• Patients with cholesterol levels ≥1.7 mmol/L showed milder symptoms and later diagnosis (9 months to 25 years).
• Intellectual disability was present in all 10 patients.
• A novel DHCR7 mutation (c.1220A>G, p.Asn407Ser) was identified.

Conclusions:

• Routine screening for adrenal insufficiency, hypoparathyroidism, hypothyroidism, and immunodeficiency is recommended for early-diagnosed SLOS infants.
• Early diagnosis and intervention for biochemical abnormalities can reduce mortality and improve long-term outcomes in SLOS patients.