From the Guidelines
Smith-Lemli-Opitz syndrome (SLOS) should be diagnosed through a combination of blood tests measuring cholesterol and 7-dehydrocholesterol (7-DHC) levels, as well as genetic testing for mutations in the DHCR7 gene, to confirm the diagnosis and initiate appropriate management. The diagnosis of SLOS is crucial for the management of the condition, as it allows for early intervention with cholesterol supplementation, which may improve growth and development [ 1 ].
Diagnostic Approach
The diagnostic approach for SLOS typically begins with a blood sample to analyze sterol levels, which can be performed at any age, including prenatally through amniocentesis or chorionic villus sampling. Patients with SLOS typically have low cholesterol and elevated 7-DHC levels [ 1 ].
Genetic Testing
Genetic testing for mutations in the DHCR7 gene, which encodes the enzyme 7-dehydrocholesterol reductase, confirms the diagnosis [ 1 ]. This enzyme is essential for converting 7-DHC to cholesterol, and its deficiency causes the characteristic biochemical abnormalities.
Clinical Considerations
For newborns or children showing symptoms like distinctive facial features, developmental delays, or congenital anomalies, testing should be promptly initiated [ 1 ]. Early diagnosis allows for earlier intervention with cholesterol supplementation (typically 20-300 mg/kg/day), which may improve growth and development, though it cannot reverse existing malformations. Patients diagnosed with SLOS require multidisciplinary care including neurology, gastroenterology, and developmental specialists to address the various manifestations of this condition [ 1 ].
Management and Outcome
The management of SLOS is focused on improving the quality of life and reducing morbidity and mortality. Cholesterol supplementation is the mainstay of treatment, and it has been shown to improve growth and development in patients with SLOS [ 1 ]. However, the long-term outcomes of patients with SLOS are still uncertain, and further research is needed to determine the most effective management strategies [ 1 ].
From the Research
Smith-Lemli-Opitz Syndrome Overview
- Smith-Lemli-Opitz syndrome is a severe developmental disorder associated with multiple congenital anomalies, caused by a defect of cholesterol biosynthesis 2.
- The syndrome is characterized by low cholesterol and high concentrations of its direct precursor, 7-dehydrocholesterol, in plasma and tissues 2, 3.
Genetic Aspects
- Mutations in the DHCR7 gene lead to deficient activity of 7-dehydrocholesterol reductase (DHCR7), the final enzyme of the cholesterol biosynthetic pathway 2, 4, 5, 6.
- The human DHCR7 gene is localized on chromosome 11q13 and its structure has been characterized 2.
- Over 150 different mutations in the DHCR7 gene have been identified, including missense, nonsense, deletions, insertions, and splice site mutations 4, 5, 6.
Diagnosis and Management
- The plasma sterol concentrations correlate with severity and disease outcome, and can be used as diagnostic biochemical hallmarks of the syndrome 2, 3.
- Therapy with simvastatin and cholesterol supplement has been shown to lead to significant improvement in laboratory findings and clinical symptoms in some patients 5.
- The diagnosis of Smith-Lemli-Opitz syndrome can be confirmed by molecular genetic analysis of the DHCR7 gene 4, 5, 6.