Ectrodactyly-Ectodermal Dyspl... Health Article

Definition

Ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome is one of more than 100 ectodermal dysplasia syndromes. EEC syndrome is characterized by deformities of the hands and feet (ectrodactyly), abnormalities of the skin, hair, and nails (ectodermal dysplasia), and cleft lip and/or cleft palate (clefting). Other symptoms include dental, eye, skin, and kidney abnormalities.

Description

Ectodermal dysplasias (ED) are a group of inherited disorders that result from problems in early development of the ectodermal layer in the embryo. Problems with the ectoderm cause the hair, teeth, nail, and glands to develop and function abnormally. EEC syndrome is characterized by deformities of the hands and feet (ectrodactyly) that are sometimes referred to as lobster-claw deformities, abnormalities of the skin, hair, and nails (ectodermal dysplasia), and cleft lip and/or cleft palate (clefting). Other abnormalities include absence of the teeth and other dental abnormalities, decreased ability to sweat, absence of tear ducts, photophobia (increased sensitivity to light), and kidney abnormalities. Most individuals with EEC syndrome have some of these abnormalities, but very few individuals have all of these abnormalities.

EEC syndrome is genetic disorder with autosomal dominant inheritance with incomplete penetrance and variable expression. It can be inherited from a parent, but many individuals are the first in their family to be affected. DNA testing is now available and may be used to clarify the diagnosis in an individual with characteristic symptoms of the syndrome.

The cosmetic concerns of EEC can have a tremendous impact on the quality of life of an individual with EEC syndrome. The facial and limb differences can be socially isolating and physically challenging. Children and adults with EEC may be socially ostracized due to their physical appearance. Many individuals erroneously assume that people with EEC syndrome have limited abilities. It is important to increase awareness with educational programs and to take proactive steps to foster self-esteem in children with EEC syndrome.

Genetic profile

EEC syndrome has autosomal dominant inheritance with incomplete penetrance and variable expression. It is caused by mutations in the p63 gene, which is located on the long arm of chromosome 3 (3q27). The p63 gene appears to be necessary for the normal development of the skin and limbs, although its exact function is not known as of 2005.

Mutations in the p63 gene are inherited in an autosomal dominant manner. Every individual has two p63 genes: one from their father and one from their mother. In an autosomal dominant disorder, only one gene has to have a mutation for the person to have the EEC disorder. Some individuals with EEC syndrome are born to unaffected parents. Their EEC syndrome is the result of a de novo, or new mutation. No one knows the cause of de novo mutations or why they occur so frequently in EEC syndrome. Because individuals pass half of their genes onto their children, a person with EEC syndrome has a 50% chance that their child will also inherit EEC syndrome. If two unaffected people have a child with EEC syndrome, they have about a 4% risk to have another child with EEC syndrome. This increased recurrence risk is due to the possibility of germline mosaicism. Germline mosaicism is the presence of two cell lines in the reproductive cells (eggs or sperm cells) of an individual. Thus, a parent of a child with EEC syndrome may have one normal cell line and one cell that contains the mutation for EEC syndrome.

While EEC syndrome has autosomal dominant inheritance, it also shows incomplete penetrance. Incomplete penetrance is the term that is used to describe individuals with a mutation in a gene that do not have any symptoms of a particular disease. Although this is very rare, there are some large families in which this phenomenon has been documented. Because the physical findings of EEC syndrome can be so variable, it is important to carefully examine other family members to make sure that they do not have an extremely mild case of EEC syndrome.

The findings or symptoms of EEC vary from family to family and even from person to person within the same family. For example, one sibling may have cleft lip and hand abnormalities, while another sibling may have kidney and eye abnormalities. This phenomenon is referred to as variable expression. Most ectodermal dysplasias show some degree of variable expression. This can often make it very difficult for a physician to make an exact diagnosis.

Demographics

The overall incidence of ectodermal dysplasias in the United States is seven out of 10,000 people. Because the findings of EEC syndrome overlap those seen in other ectodermal dysplasia, the exact prevalence of EEC syndrome is not known. With the advent of DNA testing, it may soon be possible to get an accurate prevalence figure for EEC syndrome, but, as of 2005, this is not yet possible.