Smith-Lemli-Opitz Syndrome
Description
Smith-Lemli-Opitz Syndrome (SLOS) is a rare genetic disorder that affects multiple body systems. This condition is caused by a deficiency in the enzyme 7-dehydrocholesterol reductase (DHCR7), which is crucial for the production of cholesterol. This deficiency leads to a buildup of 7-dehydrocholesterol, a cholesterol precursor, in the body. SLOS can result in a wide range of physical, cognitive, and behavioral challenges. However, with early diagnosis and proper management, individuals with SLOS can live fulfilling lives.
Genes Involved
Genes Involved: SLOS is caused by mutations in the DHCR7 gene, which provides instructions for the production of the 7-dehydrocholesterol reductase (DHCR7) enzyme. This enzyme is essential for the final step in cholesterol biosynthesis. Mutations in the DHCR7 gene disrupt the function of the DHCR7 enzyme, leading to a buildup of 7-dehydrocholesterol and the development of SLOS.
Recognizing the Signs and Symptoms
Recognizing the Signs and Symptoms: SLOS can present with a wide range of signs and symptoms, which may vary in severity from person to person. Some common signs and symptoms include:
- Physical Characteristics:
- Facial features: Microcephaly (small head), a distinctive facial appearance with a prominent forehead, small jaw, and widely spaced eyes
- Hand and foot abnormalities: Syndactyly (webbed fingers or toes), polydactyly (extra fingers or toes), and short fingers or toes
- Heart defects: Patent ductus arteriosus (a hole in the heart), ventricular septal defect (a hole in the wall between the heart chambers)
- Genital abnormalities: Hypospadias (an opening of the urethra on the underside of the penis) in males, and ambiguous genitalia in some cases
- Cognitive and Behavioral:
- Developmental delays: Delays in speech, motor skills, and cognitive development
- Intellectual disability: Variable levels of intellectual disability ranging from mild to severe
- Behavioral issues: Anxiety, aggression, and difficulty with social interactions
- Other:
- Feeding difficulties: May experience difficulties with sucking, swallowing, and gaining weight
- Gastrointestinal issues: Frequent vomiting, diarrhea, and constipation
- Hearing and vision problems: Hearing loss and vision problems can also occur.
Causes
Causes: SLOS is a genetic disorder caused by mutations in the DHCR7 gene. These mutations are inherited from the parents. In most cases, the mutations are spontaneous, meaning they occur randomly in the egg or sperm cell during the formation of the child. However, there is also a chance of inheriting the mutated gene from one or both parents, depending on the family history.
Inheritance/recurrence risk
Inheritance or Recurrence Risk: SLOS is an autosomal recessive disorder, which means that both parents must carry a copy of the mutated gene for their child to inherit the condition. If both parents are carriers, there is a 25% chance for each pregnancy that the child will be affected by SLOS. There is a 50% chance that the child will be a carrier, and a 25% chance the child will not carry the mutation. For families with a child diagnosed with SLOS, genetic counseling is highly recommended to understand the risks of having another child with the condition.
