Smith-Lemli-Opitz syndrome (SLOS) is a rare genetic disorder that impacts the body’s ability to produce cholesterol. This condition leads to a wide range of developmental and physical challenges, affecting individuals in varied ways. Understanding SLOS provides context for its long-term health outlook.
Understanding Smith-Lemli-Opitz Syndrome
Smith-Lemli-Opitz syndrome arises from a genetic defect in the DHCR7 gene. This gene provides instructions for the enzyme 7-dehydrocholesterol reductase (DHCR7). This enzyme converts 7-dehydrocholesterol (7-DHC) into cholesterol, the final step in the body’s cholesterol synthesis pathway. When mutations occur in the DHCR7 gene, this conversion is impaired, leading to low cholesterol and an accumulation of 7-DHC.
Cholesterol is a fundamental component for cell membrane structure and function, fetal development, and the production of various hormones and digestive acids. The imbalance of low cholesterol and high 7-DHC can disrupt normal cellular processes and development, resulting in the diverse range of features observed in individuals with SLOS.
Key Factors Affecting Life Expectancy
Life expectancy for individuals with Smith-Lemli-Opitz syndrome is largely influenced by the presence and severity of specific medical complications. Infants with the most severe forms of SLOS, characterized by very low plasma cholesterol levels, may experience multi-organ system failure and often do not survive beyond the first weeks or months of life. Survival is unlikely if plasma cholesterol levels fall below approximately 20 mg/dL.
Severe congenital heart defects can lead to issues such as cyanosis or congestive heart failure. Life-threatening feeding difficulties, which can result in malnutrition or aspiration, are also a leading cause of early mortality, alongside infections, hypoglycemia, and adrenal insufficiency. Profound neurological impairments and severe respiratory problems contribute to the challenges faced by affected individuals and can impact their survival, particularly in early childhood.
Diagnosis and Management Approaches
Diagnosing Smith-Lemli-Opitz syndrome begins with clinical suspicion based on physical features and developmental delays. Biochemical testing confirms the diagnosis by measuring plasma sterol levels, which reveal elevated 7-dehydrocholesterol (7-DHC) and low cholesterol levels. Genetic testing, identifying mutations in the DHCR7 gene, provides further confirmation.
Management of SLOS focuses on addressing specific symptoms and complications, as there is currently no long-term cure. A primary intervention involves cholesterol supplementation, administered through purified preparations or high-cholesterol foods like egg yolks, cream, and butterfat. This aims to increase plasma and tissue cholesterol levels and reduce the accumulation of toxic 7-DHC.
Care for individuals with SLOS often requires a multidisciplinary team of specialists, including geneticists, cardiologists, gastroenterologists, and neurologists. Symptomatic treatments include cardiac care for heart defects, respiratory support for breathing difficulties, and nutritional interventions, which may involve feeding tubes for severe feeding problems. Physical, occupational, and speech therapies are also implemented to support development and improve overall function.
Outlook and Long-Term Considerations
The overall prognosis and long-term outlook for individuals with Smith-Lemli-Opitz syndrome are highly variable, depending heavily on the severity of their symptoms and the effectiveness of ongoing medical management. While severe cases can result in early mortality, many individuals with milder forms of SLOS can live into adulthood and beyond. Recent research indicates that affected individuals can live beyond 35 years, with about 75% surviving past this age.
Continuous, specialized medical care and proactive management of complications play a role in improving health outcomes and extending life for those with SLOS. Advancements in medical understanding and treatment strategies, including more refined approaches to cholesterol supplementation and symptomatic support, enhance the quality and length of life for individuals living with this complex disorder.