Smith-Lemli-Opitz syndrome (SLOS) is a rare genetic disorder involving several of the body’s systems. Initially reported in 1964 by Drs. David Smith, Luc Lemli, and John Opitz, SLOS is an error of cholesterol metabolism resulting in a broad spectrum of physical, mental and behavioral deficits. Despite its intricate nature, current research has enhanced the understanding of the syndrome and laid a foundation for new therapeutic approaches.
What Causes Smith-Lemli-Opitz Syndrome?
SLOS is an autosomal recessive condition, so a child must have two copies of the defective gene (one from each parent) to have it. The mutation is in the DHCR7 gene, which instructs the body to make an enzyme known as 7-dehydrocholesterol reductase. This enzyme is important in the body’s cholesterol production.
Cholesterol isn’t only crucial for heart health; it’s necessary for creating cell membranes, creating hormones as well as for the brain as well as the nervous-system’s normal growth. In SLOS, the deficient enzyme causes there to be little cholesterol and too much of the abnormal sterol precursors in the body, which are responsible for the symptoms.
Signs and Symptoms
The severity of SLOS can vary significantly, even among siblings. Symptoms may include:
Physical abnormalities:
- Unusual looking face (small head, wide bridge of the nose, droopy eyelids)
- Cleft palate
- Microcephaly (small head size)
- Additional fingers or toes (polydactyly)
- Webbing of the 2nd and 3rd toes
- Heart defects
- Malformations of gonads and related structure in males
Any developmental and behavioral issues:
- Intellectual disability
- Late in the development of speaking and moving
- Autism spectrum behaviors
- Feeding difficulties
- Sleep disturbances
Growth issues:
- Pre- and perinatal growth retardation
- Non-Growth failure in an infant
The severity of the condition may vary from mild (in which case affected individuals may have normal development) to severe (which may cause life-threatening complications in infancy).
How Is SLOS Diagnosed?
Diagnosis is often initiated upon the identification of typical physical features as well as developmental delay. SLOS Diagnosis Doctors often diagnose SLOS by:
Blood tests:
A test that measures elevated amounts of 7-dehydrocholesterol (7-DHC) and low levels of cholesterol.
Genetic testing:
Identifying Mutations in the DHCR7 gene.
Prenatal testing:
Amniocentesis or chorionic villus sampling (CVS) can diagnose increased 7-DHC levels or mutations in families with an affected sibling.
Treatment and Management
There is no effective treatment for SLOS but the symptoms are managed to increase the quality of life. Possible management can be:
- Cholesterol replacement: Cholesterol administered by mouth will increase blood cholesterol, however, the response to this treatment is variable.
- Nutrition: Feeding or feeding tubes may be used to supplement for nutritional needs.
- Therapies such as Physical, Occupational and Speech Therapies: All early intervention development programs are important to maximize ones developmental potential.
- Surgery: Some children may need surgery to repair physical abnormalities, like a cleft palate or a heart defect.
- Behavioral support: Combating autism-like behaviors and other difficulties with interventions planned supports.
A care team that includes pediatricians, geneticists, cardiologists, surgeons, therapists, and nutritionists often offers the best approach to care for those with SLOS.
What is it like to live with Smith-Lemli-Opitz Syndrome
The families of children with SLOS often face emotional, financial, and practical hardships. Support groups, counseling and meeting other families dealing with SLOS can lead to much-needed emotional support and practical advice.
Early recognition and treatment have a significant impact on quality of life for those affected by Smith-Lemli-Opitz syndrome. And progress on the research front offers hope for improved treatments, and possibly preventive strategies down the road.