Smith-Lemli-Opitz syndrome

If your child has been diagnosed with Smith-Lemli-Opitz syndrome, your doctor will most likely test you and your partner’s blood to confirm that you are carriers and to identify which change in the DHCR7 gene you carry.

Based on the results of this test, your doctor will likely recommend that you speak with other adult members of your family who are planning to have children (for example, you siblings, cousins, etc) as these individuals may also be at risk for being a carrier of the same gene change as you.

If you already have another child who does not have symptoms of Smith-Lemli-Opitz, your genetics specialist will often recommend that the child consider getting tested themselves when they turn 18 years old or when they begin planning to start their own family.

If you are considering having more children, prenatal diagnosis is available in subsequent pregnancies to determine if the baby has Smith-Lemli-Opitz.

To find a genetic professional near you who can discuss genetic testing, visit the following two sites: A listing of medical geneticists can be found at the American College of Medical Geneticists website ([link url="” target=”_blank”>www.acmg.net) and genetic counselors can be found on the National Society of Genetic Counselors website: [link url="” target=”_blank”>www.nsgc.org.

Because Smith-Lemli-Opitz syndrome is rare, you may not know anyone else with the disease in your town. You can connect with other families through online support groups such as http://www.smithlemliopitz.org/, https://www.rareconnect.org/en, and https://www.patientslikeme.com

Taking care of someone with a long-term or chronic condition can be tiring and challenging and this is no different for parents or other caregivers of people with Smith-Lemli-Opitz syndrome. If you are a caregiver in need of support, try to take time for yourself, set aside time for personal counseling, or look for other resources at the Caregiver Action Network. This organization works to improve the quality of life for people who care for loved ones with chronic conditions, disabilities, disease, or the frailties of old age. Support groups can also help provide support and advice for caregivers. Support groups for Smith-Lemli-Opitz syndrome include: The Smith-Lemli-Opitz Syndrome Association

Since Smith-Lemli-Opitz is a complex disease, and there may be many doctors involved in your child’s care. In addition to regular visits with your primary care provider, children and adults with Smith-Lemli-Opitz syndrome can benefit from routine visits with the following specialists:

Smith-Lemli-Opitz (SLO) syndrome is a rare metabolic disease. It was named for the 3 doctors who first identified the disease in patients, back in 1964: David Smith, Luc Lemli, and John Opitz.

People with SLO have a problem making cholesterol. They are missing an enzyme (called 7-dehydrocholesterol reductase) that helps our bodies synthesize or make cholesterol.

While you may have heard that too much cholesterol is bad for you, our bodies need cholesterol to grow properly both before and after birth. Because cholesterol is an important component in our cells and brains, SLO affects many parts of the body.

People with SLO typically have distinct facial features, poor growth, and developmental delays and/or mental retardation. They can also have physical malformations such as abnormally small heads, webbing between the 2nd and 3rd toes, small or abnormal genitalia in males, and problems with their organs, particularly the heart, eyes, and/or kidneys. The symptoms of SLO will be different in each person, depending on how much cholesterol their body makes. To learn more, visit: Smith-Lemli-Opitz.

Smith-Lemli-Opitz is caused by changes in the DHCR7 gene. This gene is responsible for making an enzyme known as 7-dehydrocholesterol reductase. Cholesterol plays many very important roles in the body including building cell walls, protecting nerve cells, producing hormones, and supporting healthy digestion. When there are changes in the DHCR7 gene, the enzyme does not work, and cholesterol is not produced. Deficiencies in cholesterol cause the features associated with Smith-Lemli-Opitz.

A child with Smith-Lemli-Opitz syndrome demands a lot of time and focus from parents. Although studies have shown that siblings of children with chronic illness tend to develop strong levels of compassion and empathy, these studies have also shown that siblings can develop feelings of jealousy and anger and high levels of anxiety. It is possible for healthy siblings to feel as if they have been pushed aside when parents focus more of their efforts on their child with a chronic illness. Parents should encourage healthy siblings to discuss their concerns and feelings about living with a sibling with a chronic illness. It is important for parents to acknowledge and address these concerns with their healthy children. Healthy siblings can feel more included in the family structure when they help with the care of their sick sibling. Parents are encouraged to make time for activities specifically for healthy siblings. Some siblings may benefit from support outside of the immediate family, such as meeting with a therapist. The Sibling Support Project is a nonprofit organization that serves the concerns and needs of siblings of people with special health, developmental, and mental health needs. There are also regional support groups for siblings of children with serious health conditions. Your child’s pediatrician or your local hospital may be able to tell you if this type of support group is available in your area.

The first step is to have your child diagnosed with a specific learning problem, this can help tailor assistance towards their specific needs. Your pediatrician or specialist may also have suggestions for interventions or resources that may help your child. Working with the school to set up an Individualized Education Program (IEP) for your child can help them learn and thrive in a school environment. There are resources available to help parents with children with learning difficulties such as the website Understood.

If you are concerned that your child has a behavioral problem that is not age appropriate and is on-going talk with your doctor about setting up a diagnosis with a trained professional. Behavioral treatment plans are created specifically for the child and the family so that they may also work on the skills at home. Sometimes medication may be prescribed in combination with behavioral therapy, depending on the specific issues present.

The severity of the symptoms in people with SLO varies greatly from person to person. Almost all patients with SLO will have:

If your child is diagnosed with Smith-Lemli-Opitz, the first step is to find a medical specialist that can help you identify the best care. While there is no cure for Smith-Lemli-Opitz syndrome, early diagnosis and treatment may help prevent or reduce the health issues that people with Smith-Lemli-Opitz may experience.

Seek out a family support organization in your area. Whether you find an online or in-person group, many families find relief and comfort in talking to other people who are going or have gone through similar experiences. One such group, Smith-Lemli-Opitz/RSH Foundation was founded in 1988 in the United States, and is advised by John Opitz. Speak with your genetic counselor about other support groups available for individuals with Smith-Lemli-Opitz.

Smith-Lemli-Opitz (SLO) is a highly variable disease in which can be mildly affected and only have learning difficulties to life-threatening. Not everyone will have the same early signs or symptoms. Some of the early symptoms that may appear include slow/decreased growth prenatally or after birth, 2-3 toe syndactyly (2nd and 3rd toes are attached or fused), low muscle tone (hypotonia), subtle to significant facial characteristics, and mild to severe intellectual disability. Again, this is a highly variable condition and even people in the same family may not have the same signs or symptoms.

Treating any genetic condition like Smith-Lemli-Opitz syndrome is a marathon and not a sprint; not everything can be handled right away, and it is important to celebrate the milestones. The first order of business is addressing any of a child’s immediate medical problem with a doctor. Afterward one should have a child evaluated for developmental and speech delays; knowing the specific services a child requires will help parents guide their child toward the growth they need to improve on those delays. Speech, physical, occupational and vision therapies may assist a child in this process. Furthermore, a child’s parents should speak with her school’s teachers and administrators to best accommodate her needs.

Testing for Smith-Lemli-Opitz syndrome is not part of routine newborn screening in most states. However, biochemical and molecular diagnosis can be performed right away in newborns who present with symptoms of Smith-Lemli-Opitz. To learn more about what conditions are offered on the newborn screen, visit: Newborn Screening.

Two types of testing can be used to help diagnose Smith-Lemli-Opitz.

Clinical research on Smith-Lemli-Opitz (SLO) syndrome is ongoing. Current research is focusing on:

Treatment for SLO will depend on the specific symptoms that a person has. These may include:

Not everyone with Smith-Lemli-Opitz have the same signs and symptoms. People who are mildly affected may have some abnormal physical features and learning/ behavior problems while people who are severely affected could have life-threatening symptoms, major physical abnormalities, and profound intellectual disability.

Smith-Lemli-Opitz (SLO) is caused by the body not making enough endogenous cholesterol. One thought is that supplementing (adding) cholesterol to your diet by adding foods that are high in cholesterol (ex. egg yolks) or a cholesterol supplementation in powder form (ex. SLOesterol™). Clinical trials on supplementing cholesterol have noted that in general cholesterol increases in the body and 7-dehydrocholesteroll (7DHC) and 8DHC decreases (people with SLO can have toxically high levels of 7DHC and 8DHC). However, the effect that cholesterol supplementation has on clinical outcomes (ex. physical symptoms) is debatable. If you find that adding cholesterol to your diet helps with your symptoms, then do what works for you. Talk with your doctor or nutritionist about what may work best for you.

There is currently research being done on treatments for SLO. These research studies can be found at the Smith-Lemli-Opitz Foundation and on [link url="clinicaltrials.gov” target=”_blank”>clinicaltrials.gov.

Genetic counselors are experts in both genetics as well as the psychosocial implications of having a genetic condition. The genetic counselor will sit down with you and your family and go through the family history, discuss the diagnosis of Smith-Lemli-Opitz syndrome, and help you work through what the diagnosis means for your family. Genetic counselors can help you talk with other family members about the diagnosis. Genetic counselors can also help you identify support resources available to you, and possibly even connect you with other families who are experiencing the same diagnosis. To learn more about genetic counselors and to find one near you visit the National Society of Genetic Counselors webpage.

People typically have 2 copies of their genes, one that comes from mom and one that comes from dad. Smith-Lemli-Opitz (SLO) is an autosomal recessive condition, meaning that a person needs two genetic changes in order to be affected. Carriers only have one genetic change and are not affected by SLO; they can however, pass their genetic changes onto their children.

Smith-Lemli-Opitz is inherited in an autosomal recessive pattern. Autosomal recessive means that the person who is affected has two altered non-working copies of the gene: one copy they received from mom and one from dad. People with SLO have two non-working copies of the DHCR7 gene. Their parents are called "carriers" because they have one non-working copy of DHCR7 and one normal copy of the gene. Therefore, they do not have any symptoms of the disease.

When both parents are carriers, each of their children will have a 25% chance of inheriting the non-working copy of the gene from both parents and having Smith-Lemli-Opitz. This means that each sibling of a child with Smith-Lemli-Opitz has a 25% chance of being affected, a 50% chance of being a carrier (like their parents), and a 25% chance of being unaffected and not a carrier.

During pregnancy: Doctors may be able to see physical abnormalities during a routine ultrasound that suggest a fetus may have Smith-Lemli-Opitz.

Additionally, blood tests performed on a mother during pregnancy may show unusual levels of certain chemicals, for example estriol. When biochemical levels are high, doctors may pursue further testing.

Doctors will look for chemicals, known as biochemical markers, in fetal cells that are collected during a chorionic villus sampling or amniocentesis. Specifically, they will look at cholesterol levels (which will be low in fetuses with Smith-Lemli-Opitz) and levels of 7-dehydrocholestrol (also known as 7DHC, which will be high in fetuses with SLO).

Molecular testing is also available on fetal cells. This test looks specifically for genetic changes in the DHCR7 gene.

After birth: Doctors can perform these same biochemical or molecular tests on a baby, child, or adult’s blood to diagnose Smith-Lemli-Opitz. The standard practice is to test the biochemical markers first. These are sufficient to diagnose the condition. Once the condition is confirmed and treatment is started, your doctor will recommend molecular testing to confirm the gene change that caused the disease in your family.

To find a genetic professional near you who can discuss genetic testing, visit the following two sites: A listing of medical geneticists can be found at the American College of Medical Geneticists website ([link url="” target=”_blank”>www.acmg.net) and genetic counselors can be found on the National Society of Genetic Counselors website: [link url="” target=”_blank”>www.nsgc.org.

Below is a list of resources for helping you identify research studies relating to SLO:

Your doctor and genetic specialist can help you find a center of excellence (COE) for the treatment of Smith-Lemli-Optiz. Many COEs are designed for symptom-specific care. For example, the [link url="www.kennedykrieger.org/” target=”_blank”>Kennedy Krieger Institute in Baltimore, MD has clinics that specialize in behavioral management and pediatric feeding disorders. These clinics treat patients with Smith-Lemli-Opitz as well as other diseases.

Smith-Lemli-Opitz syndrome is rare. It occurs in approximately 1 in 20,000-60,000 births. It is more common in Caucasian families of Central European descent.

Biochemical testing for 7-dehydrocholesterol (7-DHC) can be used to diagnose someone with Smith-Lemli-Opitz. If the results from the biochemical testing are unclear then genetic testing for the DHCR7 gene may be used.

Additionally, in order to learn if other family members are carriers (have one gene change, are not affected, but can pass on their gene change to their children) knowing the genetic change is important. The best way to learn what specific genetic changes run in the family is to first test the person who is affected by SLO. Once those genetic changes are known other family members can be tested to see if they carry the same genetic changes.

Other names for Smith-Lemli-Opitz syndrome are:

There are organizations across the globe who provide support for people with Smith-Lemli-Opitz syndrome and their families.