Ectodermal Dysplasias

What is an ectodermal dysplasia?

The term “ectodermal dysplasia” was first introduced in 1929 to describe a number of conditions that are present at or shortly after birth in which two or more of the body’s ectodermal structures (e.g hair, teeth, nails, sweat glands) fail to develop or grow properly (dysplasia).

However, it is not a very precise term and there are over 200 different types of ectodermal dysplasias described in the medical literature. Each subtype of ectodermal dysplasia is slightly different depending on the combination of body parts affected but to many people (including doctors) several forms of ectodermal dysplasia can look very similar.

The incidence of ectodermal dysplasias is about 7 cases per 10,000 births.

How are the ectodermal dysplasias classified?

Classification / nomenclature of ectodermal dysplasia is very heterogenous.

Some forms of ectodermal dysplasia are named after the clinicians who first described the condition. An example of such an eponym is Clouston syndrome.

Other forms of ectodermal dysplasia are named after the specific features of a condition, taking the first letter of a particular physical abnormality and making a new word. An example of such an acronym is ADULT syndrome, which encompasses Acral-Dento-Ungual-Lacrimal-Tooth syndrome.

Alternatively, some forms of ectodermal dysplasia are named after the affected structures in a particular condition. An example of such a disorder is tricho-odonto-onycho-dermal dysplasia, which encompasses abnormalities in hair, teeth, nails and skin.

In the early 1980s two doctors called Friere-Maia and Pinheiro suggested a classification which divided ectodermal dysplasias into pure ectodermal dysplasias (type A) and ectodermal dysplasia syndromes (type B).

Type A ectodermal dysplasias consist of congenital abnormalities of two or more ectodermal structures, numbered as [1] hair, [2] teeth, [3] nails and [4] sweat glands. Thus a condition such as orofaciodigital syndrome would be scored 2-3-4 because of abnormalities in teeth, nails and sweat glands.
Type B ectodermal dysplasias are defined as having an inherited abnormality in one of the four major structures plus one or more abnormalities in other ectodermal structures such as ears, lips or skin finger prints.

The most common form of ectodermal dysplasia is hypohidrotic ectodermal dysplasia (also known as Christ-Siemens-Touraine’s syndrome). This condition mostly affects boys. Sometimes the term “anhidrotic” is used instead of hypohidrotic. The choice of term depends on whether sweat glands produce no sweat or a reduced amount of sweat. However, the terms are often used interchangeably.

How do ectodermal dysplasias present?

Ectodermal dysplasia is usually diagnosed at or shortly after birth or when a child’s teeth, hair or nails fail to develop normally.

The syndromes are usually non-progressive and generally do not affect overall lifespan.

Sometimes ectodermal dysplasias can be difficult to diagnose and diagnosis may be delayed. For example, hypohidrotic ectodermal dysplasia may not present until a period of hot weather when the affected child overheats (fails to sweat normally).

The physical abnormalities that can occur in the ectodermal dysplasias vary considerably, thus, some ectodermal structures may be completely normal.

Ectodermal dysplasia may include abnormalities of:

HAIR

Hair may be very fine, sparse and light in colour. It may also be very fragile, coarse, wavy or coiled. Scalp inflammation and infections can occur in some ectodermal dysplasias.

TEETH

Teeth may be fewer in number or in some cases completely absent. When present, they may be pointed or ‘peg-shaped’ or have enamel defects with increased susceptibility to cavities and decay.

NAILS

Nail changes are common but are not present in all forms of ectodermal dysplasia. Finger and toe nails can become thin and brittle or fail to develop normally or may be absent.

SWEAT GLANDS

In some forms of ectodermal dysplasia there may be a reduced number of sweat glands which leads to difficulty in coping with increased body temperatures during hot weather or after exertion.

SKIN

The skin may be dry, thin, scaly and cracked and therefore more susceptible to bleeding and infection. Hard thickened skin can develop on the palms and soles. Sometimes finger prints (also known as dermatoglyphics) can be reduced or even absent

OTHER CLINICAL FEATURES

Ectodermal dysplasias can be associated with several other abnormalities including cleft lip and/or palate, limb malformations, visual defects such as cataracts, or hearing impairment. Certain features (or a combination thereof) may be specific to a distinct subtype of ectodermal dysplasia.

Why do ectodermal dysplasias occur?

Ectodermal dysplasias arise because of defects in genes that control the normal development of the ectodermal structures.

These gene abnormalities (known as gene mutations) can be inherited from one or both parents, or they can arise as a new genetic event.

Different types of ectodermal dysplasia are inherited in different ways and specific tests for gene mutations (if available) may help to determine the pattern of inheritance.

In general, gene mutations are common events but often they have limited physical consequences. However, the genes involved in ectodermal development have a critical role in the life of an embryo and therefore mutations in just one gene can often lead to several different ectodermal structures (hair, teeth, nails, sweat glands etc) showing faulty development.

Of the 200 or so different forms of ectodermal dysplasia, gene mutations have been identified in about 50 conditions. This means that we still don’t know the precise cause of the vast majority of the ectodermal dysplasias, although gene mutations that underlie the most common forms of ectodermal dysplasia such as hypohidrotic ectodermal dysplasia have been characterized.

Research on the ectodermal dysplasia genes is providing new insight into how many of these disorders develop. Some studies have shown specific genetic abnormalities in the way cells pass signals between one another or in the way genes switch other genes on or off. These studies are leading to a greater understanding of what causes ectodermal dysplasias and is helpful in giving a better classification of the ectodermal dysplasias and in improving genetic counseling.

How are ectodermal dysplasias diagnosed?

Most forms of ectodermal dysplasia are diagnosed clinically. Doctors assess all the ectodermal structures and then try to match the collection of abnormalities to those previously identified in other individuals. Sometimes this is very difficult and a precise diagnosis is not always possible.

For the subtypes of ectodermal dysplasia in which the abnormal gene is known, it is possible to screen DNA (mutation analysis) to find the specific gene mutation in an affected individual. This usually involves providing a blood sample from a vein in the arm taken from the affected child and both parents. From the blood cells, DNA can be isolated and then screened for mutations.

DNA testing for ectodermal dysplasias is not available in most hospitals. Screening is carried out in a relatively small number of diagnostic or research laboratories and doctors or genetic counselors often have to screen the internet to track down where the necessary screening can be done. One of the objectives of the Geneskin consortium will be to establish details and links to appropriate gene screening units so that it will be easier to find out where gene screening is carried out.

Prenatal testing is possible for some forms of ectodermal dysplasia although this needs to be discussed very carefully with genetic counselors. If the specific gene mutation(s) is/are known then it is usually possibly to have a DNA-based test at about 11 weeks’ into the pregnancy. Results usually take 2-4 days to come back. If the genetic abnormality is not known then a very few other forms of ectodermal dysplasia can be tested for prenatally (e.g. using ultrasound) but this is relevant to only a minority of families.

How are ectodermal dysplasias managed

Unfortunately, there is no cure or corrective treatment for any form of ectodermal dysplasia.

However, it is important be aware of available treatments and how best to control symptoms. Optimal management needs to be directed to whichever ectodermal structures are abnormal.

For example, individuals with hypohidrotic ectodermal dysplasia need to avoid overheating, as the lack of sweat glands can lead to severe hyperthermia.

For several individuals with ectodermal dysplasia, healthcare may be multidisciplinary and include consultation of dentists, plastic surgeons, paediatricians, dermatologists, physiotherapists and many other personnel.

In the future, it may be possible to improve some forms of ectodermal dysplasia when the affected individual is still an embryo within its mother’s womb but such goals are still confined to research laboratories at present.

Ectodermal dysplasias are both difficult and straightforward to manage. Difficulties can arise when there are uncertainties about the diagnosis or because of the rarity of the ectodermal dysplasias leading to a lack of clinical expertise. However, when careful attention is paid to all the ectodermal structures in an individual with ectodermal dysplasia it is possible to tailor optimal management based on what abnormalities are or are not actually present.

Disease type/subtype
Acro-dermato-ungual-lacrimal-tooth syndrome (ADULT syndrome)
Ankyloblepharon-ectodermal defects-cleft lip and palate syndrome (AEC syndrome)
Cartilage-hair hypoplasia syndrome
Cleft lip/palate-ectodermal dysplasia syndrome
Clouston syndrome
Congenital hypotrichosis with juvenile macular dystrophy
EEC Syndrome
Ectodermal dysplasia, pure hair and nail type
Ectodermal dysplasia, skin fragility syndrome
Ectodermal dysplasia, with ectrodactyly and macular dystrophy
Ectrodactyly-ectodermal dysplasia-cleft lip/palate syndrome (EEC syndrome)
Focal dermal hypoplasia syndrome
Hypohidrotic ectodermal dysplasia
Hypohidrotic ectodermal dysplasia, with immune deficiency
Hypohidrotic ectodermal dysplasia, with immune deficiency, osteopetrosis and lymphoedema
Incontinentia pigmenti
Limb-mammary syndrome
Naegeli syndrome
Rapp-Hodgkin syndrome