Ectodermal Dysplasia: Classification, Pathophysiology, Genetic Predispocisión and Clinical Recognition

The tissues mainly involved are the skin and its appendages (hair follicles, eccrine glands, sebaceous glands, nails) and teeth.

Ectodermal dysplasias (ED) comprise a large and heterogeneous group of hereditary disorders that are defined by primary defects in the development of 2 or more tissues derived from the embryonic ectoderm.

Ectodermal dysplasias are congenital, diffuse and non-progressive. To date, more than 192 different disorders have been described.

The most common Ectodermal Dysplasias are recessive hypohidrotic ectodermal dysplasia linked to the X chromosome (Christ-Siemens-Touraine syndrome), and hydropic ectodermal dysplasia ( Clouston syndrome ).

The current classification of Ectodermal Dysplasias is based on clinical characteristics.

Pure Ectodermal Dysplasias are manifested by defects in ectodermal structures alone, whereas syndromes of ectodermal dysplasia are defined by the combination of ectodermal defects in association with other abnormalities.

Classification

Their original classification system stratified the Ectodermal Dysplasias in different subgroups according to the presence or absence of:

  • Hair abnormalities or tricodisplasias.
  • Dental anomalies.
  • Abnormalities in the nails or onychodysplasias.
  • Dysfunction of the eccrine gland or dyshidrosis.

In general, Ectodermal Dysplasias were classified into group A disorders, which were manifested by defects in at least 2 of the 4 classic ectodermal structures defined above, with or without other defects and disorders of group B, which were manifested by a defect in a classic ectodermal structure.

Eleven subgroups of group A were defined, each with a different combination of 2 or more ectodermal defects (eg, 2-4, 1-2-3, 1-2-3-4).

Disorders of group B were indicated as 1-5, 2-5, 3-5 or 4-5.

With the recent identification of the genetic defect causing several ectodermal dysplasias, newer classification systems have been devised.

In 2003, Ectodermal Displasias were reclassified in the following 4 functional groups based on the underlying pathophysiological defect:

  • Communication and signaling cell by cell.
  • Accession.
  • Development

Other classification systems classify Ectodermal Dysplasias based on defects in cell signaling and communication, adhesion, regulation of transcription or development.

Several syndromes of ectodermal dysplasia may manifest in association with defects of the middle facial third, mainly cleft lip, cleft palate, or both.

The 3 most commonly recognized entities are:

  1. Ectodermal dysplasia, ectrodactyly and cleft syndrome.
  2. Hay-Wells or ankyloblephalic syndrome, ectodermal dysplasia and cleft lip / palate syndrome.
  3. Rapp-Hodgkin syndrome, all of which are caused by mutations in the TP63 gene.

 Pathophysiology

Ectodermal dysplasia is the result of abnormal morphogenesis of the cutaneous or oral embryonic ectoderm (ie, hair, nails, teeth, eccrine glands).

In some forms, mesodermal abnormalities are also present. The features include the following:

Hair defects: a reduction in the number of hair follicles can be observed along with structural anomalies of the hair shaft.

The structural abnormalities of the hair shaft can be the result of aberrations in the formation of the hair bulb and include longitudinal grooves, hair shaft torsion and cuticle wrinkles. Capillary bulbs may be distorted, bifid or small.

Eccrine defects: the eccrine sweat glands may be absent or scarce and rudimentary, particularly in patients with hypohidrotic ectodermal dysplasia.

Other defects of the secretory glands: hypoplasia of the salivary, sebaceous and lacrimal glands may occur . In some patients, the mucous glands may be absent in the upper respiratory tract and in the bronchi, esophagus and duodenum.

Dental defects: abnormal morphogenesis or absence of teeth can occur, as well as defects in the enamel.

Dystrophy of the nails: the abnormal formation of the nail plate can result in brittle, thin, fluted or very deformed nails.

Genetic predispocisión

Although it has a known genetic etiology, the number of syndromes of ectodermal dysplasia with an identifiable genetic base is increasing.

In 2009, 64 genes and 3 chromosomal loci were associated with 62 ectodermal dysplasias.

The frequency of the different Ectodermal Dysplasias in a given population is very variable. The prevalence of hypohidrotic ectodermal dysplasia, the most common variant, is estimated at 1 case per 100,000 births.

Ectodermal dysplasias have been described more frequently in white-skinned people, but they have also been observed in people of other races. Hydrocytic ectodermal dysplasia has been reported in a large family of French-Canadian origin.

X-linked recessive hypohidrotic ectodermal dysplasia has complete expression only in males.

Carriers outnumber affected men, but women show few or no signs of the condition.

X-linked recessive anhydrotic ectodermal dysplasia (EDA) with immunodeficiency (EDA-ID) and X-linked recessive syndrome of osteopetrosis, lymphedema, EDA and immunodeficiency (OL-EDA-ID) are also observed exclusively in males.

The remaining Ectodermal Dysplasias have no sexual predilection.

Clinical recognition

Clinical recognition of ectodermal dysplasia varies from birth to childhood, depending on the severity of the symptoms and the recognition of associated complications.

Many patients are not diagnosed until infancy or childhood, when dental anomalies, nail abnormalities or alopecia become evident.

The syndrome of AEC or Hay-Wells can be manifested at birth as anquilofilán in association with chronic erosions of the scalp.

Hypohidrotic ectodermal dysplasia can manifest as desquamation and erythema at birth.

Patients with anhidrosis or hypohidrosis may present in early childhood with recurrent episodes of hyperpyrexia .