Sotos syndrome

Sotos syndrome is inherited in an autosomal dominant manner. This means that having a mutation in only one of the 2 copies of the responsible gene (the NSD1 gene) is enough to cause signs and symptoms of the condition.

95% of people with Sotos syndrome do not inherit the condition from a parent. In these cases, the condition is the result of a new (de novo) mutation that occurred for the first time in the affected person. Only about 5% of people with Sotos syndrome have an affected parent and inherit the condition from that parent.

If a parent of an affected person with an identified NSD1 mutation does not have any features of Sotos syndrome, that parent is very unlikely to have a mutation in the gene. This can be confirmed with genetic testing if the mutation has been identified in the child.

If a person with Sotos syndrome has children, each child has a 50% (1 in 2) chance to inherit the mutation. However, the specific features and severity can vary from one generation to the next, so it is not possible to predict how a child will be affected.^[1]

To date, no NSD1 mutations have been identified in an unaffected parent or unaffected sibling of a person with Sotos syndrome caused by a mutation in the NSD1 gene. This means that Sotos syndrome appears to have full penetrance. It is assumed that every person with a mutation in the responsible gene will have features of the condition.^[1] Due to the fact that only 5% of affected people inherit Sotos syndrome from a parent and the condition is apparently fully penetrant, siblings confirmed to be unaffected may not need to be tested for the condition. However, the features and severity of Sotos syndrome can be variable. Therefore, people with questions about the underlying cause of Sotos syndrome in their family and genetic risks to themselves or family members should speak with a genetics professional about genetic testing.

The term 'autosomal dominant' means that having a disease-causing mutation in only one of the two copies of the responsible gene is sufficient to cause the condition. The term does not necessarily imply that the mutated gene must be inherited from an affected parent.

In many people with an autosomal dominant condition, the disease-causing mutation occurs sporadically for the first time in the affected person. This is called a de novo mutation. However, once a person has a mutation, they then have a 50% chance to pass it on to each of their children. For some conditions (such as Sotos syndrome), only a very small proportion of people inherit the condition from a parent; most cases result from new mutations in the gene in people with no family history of the condition. If the child of a person with an autosomal dominant condition does not inherit the mutated gene, they cannot pass the mutated gene to their offspring.

Some conditions greatly impair physical and/or intellectual abilities; others may shorten the lifespan so that affected people do not reach reproductive age. In these cases, it may be unlikely that an affected person would pass the mutated gene on to offspring. However, the condition is still considered autosomal dominant because having a mutation in only one copy of the responsible gene is sufficient to cause the condition.

Yes. The features of Sotos syndrome can vary among affected people. At least 90% of affected people have the 'cardinal' features of the condition, which include a characteristic facial appearance, learning disability, and overgrowth. While the majority have some degree of intellectual impairment, this may range from having a mild learning disability (ultimately living independently and having a family) to a severe learning disability (being unable to live independently as an adult). Many other features may also occur in a smaller proportion of people and may also range in severity.^[1]

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.