Smith-Lemli-Opitz syndrome (SLOS) is a variable genetic disorder that is characterized by slow growth before and after birth, small head (microcephaly), mild to moderate mental retardation and multiple birth defects including particular facial features, cleft palate, heart defects, fused second and third toes, extra fingers and toes and underdeveloped external genitals in males. The severity of SLOS varies greatly in affected individuals, even in the same family, and some have normal development and only minor birth defects. SLOS is caused by a deficiency in the enzyme 7-dehydrocholesterol reductase that results in an abnormality in cholesterol metabolism. SLOS is inherited as an autosomal recessive genetic disorder.

The features of SLOS are not the same in every patient. Common findings are slowed growth before and after birth, a Small head (microcephaly) and a spilt in the roof of the mouth (cleft palate). Most babies have differences in their fingers and/or toes. This includes Fused toes (2-3 syndactyly) and extra fingers or toes (polydactyly). Males with SLOS can have underdeveloped genitals that may resemble female genitals. People with SLOS often experience behavioral problems, sleep problems and mild to severe intellectual disability.

Individuals with SLOS have specific facial features. Their eyes may appear to be drooping (ptosis). There can also be a fold in the inner corner of the eye (epicanthal folds) and wrinkles on the eyelids. Children with SLOS can have a small nose and nostril differences (anteverted nares). Other common facial features include differences of the upper lip, a small jaw and large ears. Vision problems can occur, including cataracts. There may also be differences in the number and/or spacing of teeth.

Less common findings include seizures, Heart defects and low muscle tone (hypotonia). People with SLOS can have a narrowing at the top of the stomach (pyloric stenosis) and blockage (obstruction) of the bowel. A Sensitivity to light (photosensitivity) is also common.

The chromosomes in our cells carry our genes which occur in pairs and are instructions to make proteins. One copy of each gene is inherited from the mother, and the other from the father. SLOS is caused by having a harmful change (mutation) in both copies of the DHCR7 gene. This causes lack of an enzyme (7-dehydrocholesterol reductase) which is needed to make cholesterol. Cholesterol is a waxy substance that is important for making cell structures. Cholesterol is necessary for development before and after birth. Mistakes in DHCR7 also leads to a buildup of 7-dehydrocholesterol (7-DHC) which is toxic to the body. Buildup of 7-DHC along with low cholesterol cause the features of SLOS.

SLOS is an autosomal recessive genetic condition. Recessive genetic conditions occur when an individual inherits a non-working gene from each parent. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass on the non-working gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive working genes from both parents is 25%. The risk is the same for males and females.

Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same harmful gene change, which increases the risk to have children with a recessive genetic condition.

Treatment for SLOS is based on the child’s specific problems. Some children may require surgery to correct cleft palate, heart defects and genital anomalies. Early educational intervention is important for learning and developmental disabilities. Food with extra cholesterol and bile acid supplements may improve some of the symptoms of SLOS including growth. Statins, such as Simvastatin, can safely reduce DHC levels and may improve some behavioral problems.