Smith-Lemli-Opitz syndrome: what is it, symptoms, treatment, prognosis

What is Smith-Lemli-Opitz Syndrome?

Smith-Lemli-Opitz Syndrome (abbr. CRO, 7-dehydrocholesterol reductase deficiency) Is a variable genetic disorder characterized by slow growth before and after birth, small head (microcephaly), mild to moderate mental retardation and multiple birth defects, including certain facial features, cleft palate, heart defects, fused fingers of the second and third fingers, extra fingers and toes, and underdeveloped external genitals in men. The severity of FMDF varies greatly among patients, even among the same family, and some have normal development and only minor birth defects. CCLO is caused by a deficiency of the enzyme 7-dehydrocholesterol reductase, which leads to impaired cholesterol metabolism. The disease is inherited as an autosomal recessive genetic disorder.

Signs and symptoms

Symptoms of Smith-Lemli-Opitz syndrome vary greatly between patients, but a typical pattern of abnormalities includes:

• growth retardation;
• microcephaly;
• extra fingers and toes;
• fusion of the second and third toes;
• cleft palate;
• underdevelopment of the external genital organs in men;
• mental retardation.

Facial features associated with a deficiency of the enzyme 7-dehydrocholesterol reductase include drooping eyelids, folds in the inner corners of the eyes, fine wrinkles on the skin of the upper and lower eyelids, nostrils turned forward, a long upper lip, an inverted V-shaped upper lip, a small jaw and large outer ears. Sometimes gingival abnormalities are present and some patients have various visual impairments, including cataract.

Occasional findings include:

• epilepsy;
• heart defects;
• low muscle tone (hypotension) in young children;
• Narrowing of the distal opening of the stomach (pyloric stenosis);
• intestinal obstruction.

Many people with Smith-Lemli-Opitz syndrome have unusual painful eye sensitivity to light (photophobia).

Causes and risk factors

CCLO is caused by a deficiency of the enzyme 7-dehydrocholesterol reductase. An enzyme deficiency results from a gene mutation DHCR7inherited from each parent.

Smith-Lemli-Opitz syndrome is an autosomal recessive genetic disorder. Recessive genetic disorders occur when a person inherits the same abnormal gene for the same trait from each parent. If a person receives one normal gene and one gene for the disease, they will be a carrier of the disease, but usually not asymptomatic. The risk for two carrier parents of passing on the defective gene and therefore having a sick child is 25% with every pregnancy. The risk of having a child who will be a carrier, like the parents, is 50% with every pregnancy. The probability that a child will receive normal genes from both parents and be genetically normal for this trait is 25%. The risk is the same for men and women.

All humans carry 4 to 5 abnormal genes. Parents who are close relatives (blood relatives) have more risks than unrelated ones parents who have the same abnormal gene, which increases the risk of having children with a recessive genetic disease.

Affected populations

The prevalence of 7-dehydrocholesterol reductase enzyme deficiency at birth is estimated to be about 1 in 20,000–60,000 live births. Predicted prevalence based on newborn screening for carriers of the gene is estimated from 1 in 1590 to 13 500, and this discrepancy may be due to the fact that many fruits with CFO are born stillborn. This condition occurs equally in men and women, but in women it is often not diagnosed because genital abnormalities are not visible. CFO is more common in people of European descent.

Diagnostics

The diagnosis of CCLO is based on physical signs and the detection of an elevated serum 7-dehydrocholesterol (7-DHC) concentration or an elevated 7-dehydrocholesterol to cholesterol ratio. Molecular genetic testing for gene mutations DHCR7 available and mainly used for media testing and prenatal diagnostics.

Standard treatments

Medical treatment for Smith-Lemli-Opitz syndrome is based on the specific problems the affected child has. It is important that the child is examined for a variety of conditions associated with CFO, including diseases of the eyes, heart, musculoskeletal system, of the genitourinary system and gastrointestinal tract, and that care is monitored by a specialist doctor familiar with the deficiency of the enzyme 7-dehydrocholesterol reductase. Patients with severe illnesses may need surgery to correct cleft palates, heart defects, and genital abnormalities. Cholesterol supplements (one or two egg yolks), sometimes combined with bile acids, appear to improve growth and reduce photosensitivity in people with CFO without harmful side effects.

Genetic counseling is recommended for the parents of the affected child.

Forecast

The prognosis depends on the severity of the disease and associated malformations. Heart disease and malformations of the brain can be fatal. Some patients live into adulthood. Patients with a mild degree of injury can live and work at home.

Complications

Many potential complications are recognized. Virtually every cell in the body depends on cholesterol to maintain normal function; therefore, cholesterol deficiency in patients with Smith-Lemli-Opitz syndrome can affect every organ.

Those most severely affected by the syndrome either spontaneously miscarry or die in the neonatal period despite maximum therapy.

Surviving patients may have renal failure, adrenal insufficiency, epilepsy, developmental delay and dysfunction liver.