Ectodermal Dysplasia 

  • Author: Kara N Shah, MD, PhD; Chief Editor: Dirk M Elston, MD   more...
 
Updated: Jan 24, 2012
 

Background

The ectodermal dysplasias (EDs) comprise a large, heterogeneous group of inherited disorders that are defined by primary defects in the development of 2 or more tissues derived from embryonic ectoderm. The tissues primarily involved are the skin, hair, nails, eccrine glands, and teeth. Although Thurnam published the first report of a patient with ectodermal dysplasia in 1848,[1] the term ectodermal dysplasia was not coined until 1929 by Weech.[2]

The ectodermal dysplasias are congenital, diffuse, and nonprogressive. To date, more than 192 distinct disorders have been described. The most common ectodermal dysplasias are X-linked recessive hypohidrotic ectodermal dysplasia (Christ-Siemens-Touraine syndrome), as shown in the image below, and hidrotic ectodermal dysplasia (Clouston syndrome).

A newborn boy with anhidrotic/hypohidrotic ectoderA newborn boy with anhidrotic/hypohidrotic ectodermal dysplasia syndrome showing generalized fine scaling and a history of intermittent fever.

Current classification of ectodermal dysplasias is based on clinical features. Pure ectodermal dysplasias are manifested by defects in ectodermal structures alone, while ectodermal dysplasia syndromes are defined by the combination of ectodermal defects in association with other anomalies.

Freire-Maia and Pinheiro proposed the first classification system of the ectodermal dysplasias in 1982,[3] with additional updates in 1994 and 2001.[4, 5] Their original classification system stratified the ectodermal dysplasias into different subgroups according to the presence or absence of (1) hair anomalies or trichodysplasias, (2) dental abnormalities, (3) nail abnormalities or onychodysplasias, and (4) eccrine gland dysfunction or dyshidrosis.

Overall, the ectodermal dysplasias were classified into either group A disorders, which were manifested by defects in at least 2 of the 4 classic ectodermal structures as defined above, with or without other defects, and group B disorders, which were manifested by a defect in one classic ectodermal structure (1-4 from above) in combination with (5) a defect in one other ectodermal structure (ie, ears, lips, dermatoglyphics). Eleven group A subgroups were defined, each with a distinct combination of 2 or more ectodermal defects (eg, 2-4, 1-2-3, 1-2-3-4 from above). The group B disorders were indicated as 1-5, 2-5, 3-5, or 4-5 (from above).

With the recent identification of the causative genetic defect for a number of the ectodermal dysplasias, newer classification systems have been devised. In 2003, Lamartine reclassified the ectodermal dysplasias into the following 4 functional groups based on the underlying pathophysiologic defect: (1) cell-to-cell communication and signaling, (2) adhesion, (3) development, and (4) other.[6] Similarly, in 2001, Priolo and Laganà reclassified the ectodermal dysplasias into 2 main functional groups: (1) defects in developmental regulation/epithelial-mesenchymal interaction and (2) defects in cytoskeleton maintenance and cell stability.[7] Other classification systems categorize the ectodermal dysplasias based on defects in cell-cell communication and signaling, adhesion, transcription regulation, or development.[8]

Several ectodermal dysplasia syndromes may manifest in association with midfacial defects, mainly cleft lip, cleft palate, or both. The 3 most commonly recognized entities are (1) ectodermal dysplasia, ectrodactyly, and clefting (EEC) syndrome[9] ; (2) Hay-Wells syndrome or ankyloblepharon, ectodermal dysplasia, and cleft lip/palate (AEC) syndrome; and (3) Rapp-Hodgkin syndrome, all of which are caused by mutations in the TP63 gene. See the images below.

Ectodermal dysplasia, ectrodactyly, and clefting sEctodermal dysplasia, ectrodactyly, and clefting syndrome. Light-colored hair and scalp and earlobe defects are observed. Cleft lip and palate results in a characteristic nasal contour. Ectrodactyly observed in an individual with ectodeEctrodactyly observed in an individual with ectodermal dysplasia, ectrodactyly, and clefting syndrome. Typical cleft lip/palate and maxillary hyperplasiaTypical cleft lip/palate and maxillary hyperplasia in a patient with Rapp-Hodgkin syndrome.
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Pathophysiology

Ectodermal dysplasia results from the abnormal morphogenesis of cutaneous or oral embryonal ectoderm (ie, hair, nails, teeth, eccrine glands). Note the following:

  • Hair defects: A reduction in the number of hair follicles in conjunction with structural hair shaft abnormalities may be seen. Structural hair shaft abnormalities may result from aberrations in hair bulb formation and include longitudinal grooving, hair shaft torsion, and cuticle ruffling. Hair bulbs may be distorted, bifid, or small.[10]
  • Eccrine defects: Eccrine sweat glands may be absent or sparse and rudimentary, particularly in patients with hypohidrotic ectodermal dysplasia.[10, 11]
  • Other secretory gland defects: Hypoplasia of the salivary and lacrimal glands may occur. In some patients, 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 may occur.[12]
  • Nail dystrophy: Abnormal nail plate formation may result in brittle, thin, ridged, or grossly deformed nails.
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Epidemiology

Frequency

United States

The frequency of the different ectodermal dysplasias in a given population is highly variable. The prevalence of hypohidrotic ectodermal dysplasia, the most common variant, is estimated to be 1 case per 100,000 births.

International

Collectively, the prevalence of ectodermal dysplasia is estimated at 7 cases per 10,000 births.

Mortality/Morbidity

Morbidity and mortality is related to the absence or dysfunction of eccrine and mucous glands. Beyond early childhood, life expectancy ranges from normal to slightly reduced. Note the following:

  • Intermittent hyperpyrexia may occur in infants with decreased sweating. The mortality rate approaches 30%. Recurrent high fever may also lead to seizures and neurological sequelae.
  • Pharyngitis, rhinitis, cheilitis, and dysphagia may result from reduced numbers of functional mucous glands in the respiratory and gastrointestinal tracts.
  • Growth failure is common.[13]
  • Severe inflammatory scalp dermatitis with erosions may result in frequent infections and cause scarring alopecia in patients with AEC (Hay-Wells) syndrome and Rapp-Hodgkin syndrome.
  • Patients with associated immunodeficiency are at risk for recurrent infections, which may be life threatening.

Race

The ectodermal dysplasias have been reported most often in whites, but they have also been observed in persons of other races. Hidrotic ectodermal dysplasia has been reported in an extensive kindred of French-Canadian origin.

Sex

X-linked recessive hypohidrotic ectodermal dysplasia has full expression only in males. Female carriers outnumber affected men, but females show little or no signs of the condition. X-linked recessive anhidrotic ectodermal dysplasia (EDA) with immunodeficiency (EDA-ID) and the X-linked recessive syndrome of osteopetrosis, lymphedema, EDA, and immunodeficiency (OL-EDA-ID) are also seen exclusively in males. The remaining ectodermal dysplasias have no sexual predilection.

Age

Clinical recognition of ectodermal dysplasia varies from birth to childhood depending on the severity of symptoms and the recognition of associated complications. Many patients are not diagnosed until infancy or childhood, when dental anomalies, nail abnormalities, or alopecia become apparent.

AEC or Hay-Wells syndrome may manifest at birth as ankyloblepharon in association chronic scalp erosions. Hypohidrotic ectodermal dysplasia may manifest as scaling and erythema at birth. EEC syndrome and other related ectrodactyly syndromes (eg, acro-dermato-ungual-lacrimal-tooth [ADULT] syndrome and limb-mammary syndrome) are usually recognized at birth as a result of the characteristic limb deformities. Patients with anhidrosis or hypohidrosis may present in early infancy with recurrent episodes of hyperpyrexia.

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Contributor Information and Disclosures
Author

Kara N Shah, MD, PhD  Associate Professor, Departments of Pediatrics and Dermatology, University of Cincinnati College of Medicine; Medical Director, Pediatric Dermatology, Cincinnati Children's Hospital

Kara N Shah, MD, PhD is a member of the following medical societies: American Academy of Dermatology, American Academy of Pediatrics, and Society for Pediatric Dermatology

Disclosure: Nothing to disclose.

Specialty Editor Board

Jean Paul Ortonne, MD  Chair, Department of Dermatology, Professor, Hospital L'Archet, Nice University, France

Jean Paul Ortonne, MD is a member of the following medical societies: American Academy of Dermatology and American Dermatological Association

Disclosure: Nothing to disclose.

Michael J Wells, MD  Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine

Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Texas Medical Association

Disclosure: Nothing to disclose.

Van Perry, MD  Assistant Professor, Department of Medicine, Division of Dermatology, University of Texas School of Medicine at San Antonio

Van Perry, MD is a member of the following medical societies: American Academy of Dermatology and American Society for Laser Medicine and Surgery

Disclosure: Nothing to disclose.

Catherine M Quirk, MD  Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania

Catherine M Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD  Director, Ackerman Academy of Dermatopathology, New York

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

The authors and editors of eMedicine gratefully acknowledge the contributions of previous Chief Editor, William D. James, MD, and previous author, Carola Duran-McKinster, MD, to the development and writing of this article.

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A newborn boy with anhidrotic/hypohidrotic ectodermal dysplasia syndrome showing generalized fine scaling and a history of intermittent fever.
Wrinkled, hyperpigmented skin around the eyes and everted lips are typical characteristics of anhidrotic/hypohidrotic ectodermal dysplasia syndrome.
Typical cleft lip/palate and maxillary hyperplasia in a patient with Rapp-Hodgkin syndrome.
Abnormal hair shaft showing pili torti and a longitudinal groove (pili canaliculi) from a patient with Rapp-Hodgkin syndrome.
Hands of father and son with Rapp-Hodgkin syndrome. Nails have the same characteristics; they are brittle, thin, and dystrophic.
Ectodermal dysplasia, ectrodactyly, and clefting syndrome. Light-colored hair and scalp and earlobe defects are observed. Cleft lip and palate results in a characteristic nasal contour.
Ectrodactyly observed in an individual with ectodermal dysplasia, ectrodactyly, and clefting syndrome.
 
 
 
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