An Overview of Smith Lemli Opitz Syndrome

Smith Lemli Opitz syndrome is a congenital developmental disorder characterized by distinctive facial features, intellectual and learning disability, behavioral issues, and small head (microcephaly), among other manifestations. Alongside malformations of important organs like the kidneys, heart, genitals, and intestinal tract, children with this condition display characteristics of autism and attention deficit hyperactivity disorder (ADHD). A majority of those with the condition have fused-together second and third toes, and some may have extra fingers. The condition is relatively rare, affecting about one in every 20,000 to 60,000 infants.

Symptoms

The signs of Smith Lemli Opitz syndrome are present at birth, and their severity varies a great deal. In 80 percent to 99 percent of these cases. these characteristics are seen:

• Webbed toes: A common feature of the condition is fusing between the second and third toes, a condition called “syndactyl.”
• Intellectual disability: While the degree of this can vary, this condition often leads to learning disabilities.
• Abnormally small skull: Smaller than average skull size, a condition called microcephaly, is another hallmark.
• Abnormal facial features: Those with Smith Lemli Opitz syndrome have characteristic facial features including a smaller lower jaw and a wide, flat nose. In rarer cases, individuals may have drooping eyelids, cat eyes, small or absent eyes, as well as a wide mouth.   
• Difficulty feeding: In infants, this condition can lead to difficulty breastfeeding, affecting development.
• Lower muscle tone: A common characteristic of the syndrome is a lower than average muscle tone.

There are numerous less frequent symptoms, occurring in anywhere from 5 percent to 79 percent of cases, including:

• Dental development abnormalities: Early eruption of adult teeth and enlarged gums are signs of Smith Lemli Opitz syndrome.
• Ambiguous genitals: The genitals of those affected may be less defined. Males are more likely to experience this, with an under-developed penis and undescended testes.
• Attention deficit hyperactivity disorder (ADHD): This developmental disorder is characterized by difficulty regulating behavior and impulses as well as hyperactivity.
• Autism: Also known as autism spectrum disorder (ASD), this condition leads to impaired social skills, speech, and nonverbal communication abilities as well as repetitive behaviors.
• Heart defects: Heart defects associated with Smith Lemli Opitz syndrome include the development of a hole in the wall between the two upper chambers (atrial septal defect), or one between lower chambers (ventricular septal defect).
• Altered hand anatomy: Those with the condition may have extra small fingers and toes. In addition, the position of the thumb may also be atypical in that it’s closer to the wrist. Webbed fingers have also been reported. Claw hand, an atypical curvature of fingers, has also been reported.
• Photosensitivity: In many cases, the skin of those affected is extra-sensitive to sunlight.
• Frequent infection: People with the syndrome are at elevated risk for bacterial infection.
• Cleft tongue: In approximately five to 30 percent of cases, those affected will have cleft tongue, in which the tip is split.
• Abnormalities in the spine: Along with other deformities in the vertebrae, scoliosis—a lateral curvature of the spine—as well as kyphosis, or hunchback, can also accompany the condition.
• Seizures: People with this condition are more prone to develop seizures.
• Involuntary eye movements: Uncontrolled and rapid eye movements (nystagmus) may also accompany the syndrome.

Causes

Smith Lemli Opitz syndrome is a genetic disorder caused by mutation of the DHCR7 gene. This gene regulates the important enzyme, 7-dehydrocholesterol reductase, which is involved in the production of the body’s cholesterol. Among its functions, cholesterol is a major component of cell membranes and helps form myelin, a substance which protects brain cells (neurons). It also plays a significant role in proper digestion.

DHCR7 mutation causes a lack of 7-dehydrocholesterol reductase causing deficits in cholesterol production. It also allows toxic byproducts of cholesterol to build up within the body, which hinders development and growth in multiple bodily systems. The exact mechanism of how this lack of cholesterol leads to Smith Lemli Opitz syndrome is still being researched.

A genetic defect, this condition follows what’s called an “autosomal recessive pattern,” which means that both copies of the gene—one from each parent—is necessary for it to develop. This means that parents of those with the condition carry the gene, but do not necessarily have symptoms themselves.

Diagnosis

As with other congenital diseases, diagnosis of Smith Lemli Opitz involves an assessment of physical symptoms as well as testing for the ratio of 7-dehydrocholesterol reductase to cholesterol. This is done using blood tests of suspected cases. In addition, prenatal genetic testing can also detect the mutations of the DHCR7 gene that lead to the development of the condition.

Treatment

Taking on this condition involves a coordinated effort; since there’s no direct cure for this condition, symptoms and manifestations need to be effectively managed. Such approaches include:

• Cholesterol supplementation: While there’s more research needed to assess the efficacy of this approach, a diet rich in cholesterol—alongside taking supplements—may help reduce some symptoms.
• Physical therapy: Physical and occupational therapy approaches, when delivered in a timely manner, can help with disabilities associated with the condition.
• Medical treatments: Approaches are available to take on some of the physical symptoms of Smith Lemli Opitz syndrome, including digestive difficulties, visual problems, as well as facial and other deformities.
• Surveillance: Successful management of this condition requires consistent monitoring of physical symptoms, developmental delays, and dietary factors.

Prognosis

The good news is that, if Smith Lemli Opitz syndrome is properly managed and adequate medical care delivered, those with the condition have the potential to have a normal life expectancy. That said, independent living is unlikely due to the severe intellectual disability that often accompanies this syndrome. Notably, survivability for infants with severe symptoms is severely impacted, and there’s a chance of death within a couple of months.

Coping

A major congenital disorder like Smith Lemli Opitz syndrome represents a significant challenge for the person affected, their family, and doctors alike. Even though successful management is possible, there’s no doubt that there’s significant psychological fallout from this burden. Those placed into the position of caring for someone with this disease may find counseling or disability support groups helpful. Notably, resources such as links to the latest research and support services are gathered together by the Smith Lemli Opitz/RSH Foundation.

A Word From Verywell

A condition that is this debilitating and difficult, that can affect so many aspects of quality of life, may seem overwhelming. That said, not only are existing treatment approaches to Smith Lemli Opitz syndrome constantly being refined and improved, but research into this disorder is ongoing. As the medical community learns more about the causes and effects of this condition—as well as the efficacy of treatment approaches—the prognosis and quality-of-life of those affected will only improve.