Ectodermal dysplasia

Definition

The ectodermal dysplasias are a group of hereditary conditions characterized by abnormal hair, teeth, fingernails and toenails, and sweat glands.

Description

All ectodermal dysplasias have a genetic etiology and involve abnormal development and growth of tissues derived from the ectoderm. The ectoderm is the outermost layer of the developing embryo, which gives rise to the hair, teeth, nails, and skin. More than 100 different ectodermal dysplasia conditions have been described in the medical literature. The most common of these is hypohidrotic ectodermal dysplasia, which may account for up to 80% of all ectodermal dysplasias.

Other ectodermal dysplasia conditions include ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome, hidrotic ectodermal dysplasia (Clouston syndrome), Hay-Wells syndrome, incontintentia pigmenti, Rapp-Hodgkin syndrome, tricho-dento-osseous syndrome, and tooth-nail (Witkop) syndrome. Each of these conditions appears to account for 1–4% of all ectodermal dysplasias.

Most ectodermal dysplasia conditions are associated with sparse hair that has abnormal texture. The hair may appear thin, dry and brittle. In some cases, premature balding may occur.

The teeth of those with ectodermal dysplasia are typically abnormal and reduced in number. A characteristic conical and sharply pointed tooth shape is often present. In some cases, the majority of teeth are missing.

In some ectodermal dysplasia conditions, the fingernails and toenails may be absent or abnormally formed. The nails may be thickened, thinned, brittle, or display unusual ridging or pitting.

The skin may be thin, show abnormal pigmentation, and be prone to eczema (a condition of dry skin characterized by inflammation and itching). The nasal and respiratory passages may be dry, leading to abnormal discharges and increased infections. In hypohidrotic ectodermal dysplasia, the sweat glands are reduced in number, which may lead to dangerous hyperthermia (high body temperature).

Other abnormalities that may occur in the ectodermal dysplasia conditions include amastia (absent mammary glands), cleft lip and/or palate, ectrodactyly (split hand or split foot), and abnormal bands of skin in the mouth or connecting the eyelids.

Many individuals with ectodermal dysplasia have normal cognitive function. A minority of cases may involve some degree of mental retardation. In the case of hypohidrotic ectodermal dysplasia, untreated hyperthermic episodes can lead to brain damage and cognitive impairment.

Genetic profile

Hypohidrotic ectodermal dysplasia is inherited in an X-linked recessive manner. Sixty to 75% of carrier females may show variable manifestations of the condition. The responsible gene has been named EDA; it has been mapped to the Xq12-q13.1 chromosomal region but has not yet been identified.

Incontinentia pigmenti is caused by chromosomal rearrangements disrupting the Xp11 region (type I incontinentia pigmenti) or by a gene mapping to Xq28 (type II or familial incontintentia pigmenti). Both forms appear to be lethal in males, as nearly all affected patients (97–98%) are female.

Most other ectodermal dysplasias are transmitted in an autosomal dominant fashion. Rarely, autosomal recessive transmission may occur.

The molecular genetics of the ectodermal dysplasia conditions are poorly understood. Investigation has been hampered by the great variability displayed by

many of these conditions, similar features shown by different ectodermal dysplasias, and genetic heterogeneity (different genetic alterations producing identical physical features). As with many other human genetic conditions, mouse models are being used to identify candidate genes that may be responsible for these disorders.

Demographics

The exact incidence of ectodermal dysplasia conditions has not yet been studied accurately and is not known. One published report estimated the incidence of these conditions collectively as seven per 10,000 births. The disorders have been reported in individuals and families of diverse ethnic backgrounds. One early description of an ectodermal dysplasia came from Charles Darwin, who cited a report of an affected individual from the Indian subcontinent in an 1897 publication.

Signs and symptoms

Most ectodermal dysplasia conditions cause significant dental abnormalities. In some cases, the majority of the primary (baby) and secondary (adult) teeth are missing. Teeth that are present may show a characteristic conical, pointed shape (peg-teeth), or have abnormal enamel that is prone to cavities.

Hair is often thin with an abnormal texture. In hypohidrotic ectodermal dysplasia, the scalp hair is thin during childhood and ultimately shows premature balding. Although body hair, eyebrows, and eyelashes are also sparse in this condition, beard and mustache hair are normal. Hair is also sparse in EEC syndrome. In trichodento-osseous syndrome and Hay-Wells syndrome, the hair is sparse, coarse, and wiry. Individuals with incontinentia pigmenti may have patchy, bald areas of abnormal skin on the scalp. Frequent scalp infections occur in many of the ectodermal dysplasias.

A variety of skin abnormalities may occur in ectodermal dysplasia conditions. The skin may be dry, thin, and prone to eczema, infection, cracking, bleeding, and other problems. In hypohidrotic ectodermal dysplasia, sebaceous glands (the oil glands within the skin) are absent, causing severe dryness. Increased pigmentation may occur around the eyes (in hypohidrotic dysplasia), over the joints (in hidrotic ectodermal dysplasia), or in a linear pattern over the trunk (in incontinentia pigmenti). Hyperkeratosis, or thickened skin, occurs on the palms and soles of the feet in hidrotic ectodermal dysplasia. Reddening and blistering of the skin may occur during infancy in incontintentia pigmenti. In Hay-Wells syndrome, abnormal bands of skin may occur between the upper and lower jaws and between the eyelids.

Decreased numbers of sweat glands and associated impaired sweating ability is an important feature of hypohidrotic ectodermal dysplasia. This can lead to life-threatening hyperthermia in hot environments or with physical exertion. Sweating is normal in most other ectodermal dysplasias.

Many ectodermal dysplasias involve abnormalities of the mucous membranes. Production of tears and saliva may be deficient. In hypohidrotic ectodermal dysplasia, the mucous glands in the respiratory tract may be absent or decreased in number, leading to dryness, infections and an unusual foul-smelling secretion known as ozena. In some cases, dryness of the pharynx and larynx may affect the quality of the voice.

Finger and toenails are abnormal in many of the ectodermal dysplasias. In EEC syndrome, the nails may be thin and brittle. Nails may be absent or abnormally formed in Hay-Wells syndrome, Rapp-Hodgkin syndrome, hidrotic ectodermal dysplasia, tooth and nail syndrome, and incontintentia pigmenti. Nails are normal in hypohidrotic ectodermal dysplasia.

Some individuals with ectodermal dysplasia, particularly those with EEC syndrome, may have hearing impairment.

Structural birth defects may occur in some ectodermal dysplasias. In EEC, Hay-Wells, and Rapp-Hodgkin syndromes, cleft lip and palate may occur. EEC is also characterized by split hand/split foot (or "lobster claw") malformations and genitourinary anomalies. Amastia (absence of the breast) may occur in hypohidrotic ectodermal dysplasia and breasts may be underdeveloped in incontintia pigmenti and EEC syndrome. Some individuals with incontinentia pigmenti may have defects of the eye (such as congenitally crossed eyes, cataracts, or atrophy of the optic nerve) or central nervous system (such as a small head size, mental retardation, or seizures).

Diagnosis

The diagnosis of an ectodermal dysplasia condition is typically based on clinical findings (physical examination, medical and family history). With the exception of type I incontinentia pigmenti, there are no laboratory studies that are considered diagnostic. High resolution chromosome study may be considered diagnostic for type I incontintentia pigmenti as it can reveal the X chromosome rearrangements that appear to cause the condition.

The high degree of variability within and overlap between the different ectodermal dysplasia conditions can lead to difficulty identifying the specific syndrome. The presence or absence of nail and sweat gland involvement are important distinguishing features.

In hypohidrotic ectodermal dysplasia, determining whether or not a female relative of an affected male also carries the EDA gene may be difficult. A variety of clinical tests based on sweat pore and dental analysis have been attempted, but are considered unreliable. Linkage analysis by way of tracing the Xq12-13 gene locus through the family is considered to be the best way of determining carrier status. When linkage analysis is successful, it may also be used for prenatal diagnosis.

Treatment and management

In hypohidrotic ectodermal dysplasia, males are at risk for hyperthermia and potential central nervous system damage or death. Hot environments and fevers must be avoided or managed with cooling methods, such as misting the skin with water. Air conditioning of home, school, and work environments is considered essential. The dry nasal passages may be treated with moisturizing inhalers or other solutions. Various skin treatments may be used to prevent cracking, bleeding and infection.

Early and extensive dental work is required in most ectodermal dysplasia conditions. In childhood, successive dentures may be used, while dental implants and bridges may be used in adults. Orthodontic treatment may also be necessary.

The abnormal hair in the ectodermal dysplasias is primarily a cosmetic problem and may be managed with wigs.

In EEC, Rapp-Hodgkin syndrome, and Hay-Wells syndrome, clefting of the lip and palate requires surgical correction, with treatment of any associated speech, dental, or hearing problems.

Hand and foot malformations in EEC may require orthopedic or plastic surgery, and/or occupational therapy. The abnormal skin banding that may occur in the mouth and between the eyelids in Hay-Wells syndrome also requires surgical correction.

Prognosis

Among males with hypohidrotic ectodermal dysplasia, unrecognized episodes of hyperthermia are a dangerous complication. The mortality rate during infancy and early childhood in affected, undiagnosed males is 20% due to neurologic damage associated with hyperthermic episodes. If affected males are diagnosed and managed appropriately, a normal life expectancy and normal intelligence can be expected.

Otherwise, the tissue abnormalities and birth defects that occur in the ectodermal dysplasias are usually not life-threatening.

These conditions typically do not cause mental retardation, although a minority of cases of incontinentia pigmenti and EEC syndrome may involve cognitive impairment.

Resources

PERIODICALS

Coskun, Yavuz, and Ziya Bayraktaroglu. "Ectodermal dysplasia." (Pathological Case of the Month) Archives of Pediatrics & Adolescent Medicine 151, no. 7 (July 1997): 741–2.

WEBSITES

National Foundation for Ectodermal Dysplasias. <www.nfed.org>.

Jennifer Ann Roggenbuck, MS, CGC