Ectodermal dysplasia Q82.8

In general, ectodermal dysplasia is understood to be an inherited developmental disorder of all or only some of the organs developing from the ectoderm. Ectodermal dysplasias comprise a large, heterogeneous group of more than 100 diseases with combined defects of the hair, teeth, nails and sweat glands.

In addition, mesodermal and endodermal signs and organogenesis disorders may be present.

The two classical forms are anhidrotic ectodermal dysplasia and hidrotic ectodermal dysplasia.

Ectodermal dysplasias include, for example:

• Anhidrotic ectodermal dysplasia
• Anhidrotic ectodermal dysplasia with immunodeficiency 1
• Anhidrotic ectodermal dysplasia with immunodeficiency 2
• Bart-Pumphrey syndrome
• Berlin syndrome
• CHANDS syndrome
• Chondroectodermal dysplasia
• Coffin-Lowry syndrome
• Coffin-Siris syndrome
• Ectodermal dysplasia and immunodeficiency 1
• EEC syndrome
• Greither syndrome
• Hay-Wells syndrome (AEC syndrome = ankyloblepharon ectodermal dysplasia-clefting syndrome)
• Hidrotic ectodermal dysplasia
• Oro-facio-digital syndrome
• Tricho-dento-osseous syndrome
• Tricho-rhino-phalangeal syndrome
• Witkop syndrome (hair-tooth syndrome).

Hypohidrotic ectodermal dysplasia is a genetic disorder that can be caused by mutations in one of several genes.

These include:

• EDA, EDAR, EDARADD and WNT10A.
• Mutations in the EDA gene are the most common cause of this disease, accounting for more than half of all cases.
• EDAR, EDARADD and WNT10A gene mutations each account for a smaller percentage of cases.
• In about 10 percent of people with hypohidrotic ectodermal dysplasia, the genetic cause is unknown.

The EDA, EDAR, and EDARADD genes encode proteins that work together during embryonic development. These proteins are part of a signaling pathway that is critical for the interaction between two layers of cells, the ectoderm and the mesoderm. In the early embryo, these cell layers form the basis for many of the body's organs and tissues. The interactions between the ectoderm and mesoderm are essential for the formation of various structures that arise from the ectoderm, including skin, hair, nails, teeth, and sweat glands.

Mutations in the EDA, EDAR, or EDARADD gene prevent normal interactions between the ectoderm and the mesoderm, affecting the normal development of skin, hair, nails, teeth, and sweat glands. Mutations in any of these three genes result in the major signs and symptoms of hypohidrotic ectodermal dysplasia described above.

The WNT10A gene encodes a protein that is part of a different signaling pathway (Wnt signaling pathway). The Wnt signaling pathway controls the activity of specific genes and regulates interactions between cells during embryonic development. The signaling pathway involving the WNT10A protein is critical for the development of ectodermal structures, especially teeth. The WNT10A gene mutations that cause hypohidrotic ectodermal dysplasia impair the function of the protein, disrupting the development of teeth and other structures that arise from the ectodermal cell layer.

When hypohidrotic ectodermal dysplasia is caused by mutations in the WNT10A gene, the features are more variable than when mutations occur in the EDA, EDAR, or EDARADD genes. Signs and symptoms range from mild to severe, and mutations in the WNT10A gene are more likely to result in the absence of all permanent (adult) teeth.

Affected individuals tend to have sparse scalp and body hair (hypotrichosis). The hair is often light, brittle and grows slowly. Hypohidrotic ectodermal dysplasia is also characterized by multiple missing teeth (hypodontia) or malformed teeth. The teeth that are present erupt from the gums later than usual and are often small and pointed.

Some people with hypohidrotic ectodermal dysplasia have distinctive facial features, including a protruding forehead, thick lips, and a flattened bridge of the nose. Other features of this condition may include thin, wrinkled, and dark-colored skin around the eyes, chronic skin problems such as eczema, and foul-smelling discharge from the nostrils (ozena).

Intellectual ability and growth are usually normal in people with hypohidrotic ectodermal dysplasia.

Specifically, depending on the genotype, the following symptoms occur in ectodermal dysplasias:

• Pili torti
• Hypotrichosis
• anodontia, hypodontia, enamel defects
• anonychia, onychodystrophy, onychodysplasia, onycholysis, koilonychia
• Hyperhidrosis or hypohidrosis
• Anhidrosis with fever after exertion, exposure to sun or hot food
• Ichthyosis acquisita (pseudoichthyoses)
• Facial dysmorphia, hand, foot and finger deformities ( polydactyly/syndactyly), short stature, cleft lip, jaw, palate, genital anomalies.
• Mental deficiency
• Deafness
• Ocular disorders, neurological disorders, chondrodysplasia Palmoplantar keratoses
• Ozena

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