EEC syndrome

Approximately 90% of individuals with EEC syndrome have a causative mutation identified in the TP63 _gene. The _TP63 gene codes for the p63 protein, which plays a critical role in early development of the ectoderm-the layers of tissue that develop into the skin, hair, teeth, and nails. The p63 protein is additionally thought to play a role in the development of the limbs, facial features, urinary system, and other organs. Individuals that have EEC syndrome due to a mutation in the TP63 gene are classified as having EEC syndrome type 3 (EEC3).

In approximately 10% of individuals, EEC syndrome is caused by a mutation on a region of the q (long) arm of chromosome 7. Individuals that have EEC syndrome due to a mutation on the q arm of chromosome 7 are classified as having EEC syndrome type 1 (EEC1).

Rarely, EEC syndrome can be found in individuals that do not have mutations in either the TP63 gene or the q arm of chromosome 7.

It is estimated that greater than 90% of cases of EEC syndrome are caused by mutations in the TP63 gene. The remainder are suspected to be caused by different mutations in a region on chromosome 7. Genetic testing is available to detect both mutations in the TP63 gene and in the implicated region on chromosome 7.

Genetic Testing Registry lists the names of laboratories that are performing genetic testing for EEC syndrome. To view the contact information for the clinical laboratories conducting testing click here.

Testing for individuals with a family history of EEC syndrome who may have a mutation but do not exhibit signs and symptoms of the condition may be available if the mutation in the affected family member(s) is known. Prenatal diagnosis for pregnancies at risk may also be available if the mutation in the family is known.

Please note that most of the laboratories listed through GeneTests do not accept direct contact from patients and their families; therefore, if you are interested in learning more, you will need to work with a health care provider or a genetics professional.

EEC syndrome is inherited in an autosomal dominant manner.This means that having a change (mutation) in only one copy of the responsible gene in each cell is enough to cause features of the condition.

In some cases, an affected person inherits the mutated gene from an affected parent. In other cases, the mutation occurs for the first time in a person with no family history of the condition. This is called a de novo mutation.

When a person with a mutation that causes an autosomal dominant condition has children, each child has a 50% (1 in 2) chance to inherit that mutation.

EEC can appear to be caused by a de novo mutation in some instances when an unaffected parent of an affected child has germline mosaicism. Germline mosaicism affects the genetic make- up of the egg and sperm cell only. It is estimated that unaffected parents of a child with EEC syndrome have a 4% risk of having another affected child.

EEC syndrome additionally shows reduced penetrance and variable expressivity. Reduced penetrance means that not all individuals with a mutation in the disease-causing gene will have signs and symptoms of the condition; however, in this condition, it has been reported that up to 93-98% of individuals with a mutation will have the condition. Variable expressivity means that there is a range of signs and symptoms that can occur in different people with the condition (i.e. the expression of the condition varies).

EEC syndrome has reduced penetrance, which means that not all individuals who have a mutation in the disease- causing gene will have the condition. The penetrance of EEC syndrome is estimated to be between 93% and 98%; this means that 93-98% of individuals with the mutation will be affected, while 2-7% will be unaffected. However, an unaffected individual with a mutation still has a 50% chance of passing on the mutation to each of his/her children. Even though the unaffected individual with the mutation does not exhibit any signs or symptoms, his/her children can be affected. It should be noted that because the penetrance of the condition is up to 98%, an unaffected individual with an affected parent is much more likely to have two normal copies of the gene (thereby being unable to pass the condition on to offspring) than to carry the mutation and be unaffected.

Individuals interested in learning about their specific risk to have a mutation in the disease-causing gene, or their risk to have an affected child, should consult with a genetics professional.