Ectodermal Dysplasia



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 and its appendages (hair follicles, eccrine glands, sebaceous glands, and, nails) and teeth. Although Thurnam published the first report of a patient with ectodermal dysplasia in 1848, the term ectodermal dysplasia was not coined until 1929 by Weech.[1]

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).

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A 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,[2] with additional updates in 1994 and 2001.[3, 4] 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). Visinoni tabulated a summary of the 186 defined ectodermal dysplasia syndromes classified as group A in 2009.[5]  This classification was revised in 2014 to include 163 defined ectodermal dysplasia syndromes.[6]

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.[7] 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.[8] Other classification systems categorize the ectodermal dysplasias based on defects in cell-cell communication and signaling, adhesion, transcription regulation, or development.[9]

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[10] ; (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.

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Ectodermal dysplasia, ectrodactyly, and clefting syndrome. Light-colored hair and scalp and earlobe defects are observed. Cleft lip and palate results....

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Ectrodactyly observed in an individual with ectodermal dysplasia, ectrodactyly, and clefting syndrome.

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Typical cleft lip/palate and maxillary hyperplasia in a patient with Rapp-Hodgkin syndrome.


Ectodermal dysplasia results from the abnormal morphogenesis of cutaneous and/or oral embryonal ectoderm (ie, hair, nails, teeth, eccrine glands). In some forms, mesodermal abnormalities are also present. Characteristic features include the following:

Although some ectodermal dysplasia syndromes have no known genetic etiology, the number of ectodermal dysplasia syndromes with an identifiable genetic basis is increasing. In 2009, 64 genes and 3 chromosomal loci were associated with 62 ectodermal dysplasias.[5]

Key transcription factors and intracellular signaling pathways that have been implicated in the ectodermal dysplasias include the tumor necrosis factor (TNF)-like/TNV receptor signaling pathway, which involves ectodysplasin (EDA), the EDR receptor (EDAR), the EDAR-associated death domain (EDARADD); the WNT signaling pathway; the NF-kB signally pathway, which involves the NF-kB essential modulator (NEMO); and the transcription factor p63.[14]


Ectodermal dysplasia results from the abnormal development of embryonic ectodermal structures. The genetic defects responsible for approximately 30 of the ectodermal dysplasias have been identified. However, a detailed understanding of the pathophysiology underlying most forms of ectodermal dysplasia with regards to the mechanisms by which the underlying genetic defects impact the growth and development of ectodermal structures is lacking.

X-linked recessive hypohidrotic ectodermal dysplasia (XL-HED or Christ-Siemens-Touraine syndrome) is caused by mutations in EDA, which encodes the ectodysplasin protein, a soluble ligand that activates the NF-kappaB and JNK/c-fos/c-jun signaling pathways.[15, 16] Ectodysplasin is important in promoting cell survival, growth, and differentiation. Using specialized techniques, including confocal imaging, phototrichogram analysis, and pilocarpineiontophoresis, a complete absence of eccrine ducts, a reduction in hair follicle units and hair follicle density, and a decreased growth rate of terminal hairs has been demonstrated in patients with XL-HED.[17]

Autosomal dominant and autosomal recessive hypohidrotic ectodermal dysplasia are caused by mutations in the DL gene, which encodes the EDA (ectodysplasin) receptor.[18] Autosomal recessive hypohidrotic ectodermal dysplasia may also result from mutations in the EDARADD gene, which encodes a protein that interacts with the EDA receptor. A heterozygous mutation in the TRAF6 gene has been described in a patient with hypohidrotic ectodermal dysplasia.[19]

Hidrotic ectodermal dysplasia (Clouston syndrome), which is an autosomal dominant disorder, is caused by mutations in GJB6, which encodes connexin 30, a component of intercellular gap junctions.[20]

EDA-ID and OL-EDA-ID are both caused by mutations in the NEMO gene, which encodes the regulatory subunit of the inhibitor-kappa kinase complex that regulates NF-kappaB activity.[21, 22, 23]

AEC (Hay-Wells) syndrome, Rapp-Hodgkin syndrome, EEC syndrome, limb-mammary syndrome, split hand-split foot malformation syndrome, and acro-dermato-ungual-lacrimal-tooth (ADULT) syndrome are all caused by mutations in the TP63 gene.[24, 25] p63 is a transcription factor that regulates the activity of the tumor suppressor gene TP53.

The genetic defects underlying other ectodermal dysplasias are also known. Selected examples are as follows:



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.


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


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.


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.


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.


The prognosis for most patients with ectodermal dysplasia is very good. 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.

If hypohidrosis is recognized in the neonatal period and managed appropriately, no evidence indicates that the life span for a person diagnosed with one of the common types of ectodermal dysplasia is shorter than average. 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.[46]

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.

Life span can be affected in some rare types of ectodermal dysplasia. For example, patients with ectodermal dysplasia with immunodeficiency are at risk for significant morbidity and mortality related to recurrent infections and failure to thrive.

Patient Education

Provide early guidance about temperature regulation, acceptable activities, and the risk of hyperpyrexia from febrile illnesses. Inform patients and families that antipyretics are not effective in treating hyperpyrexia associated with hypohidrosis. Instruct caregivers on proper skin care and monitoring for signs of infection in patients with chronic scalp dermatitis and erosions.

Additional information and support for families is available through the National Foundation for Ectodermal Dysplasias.


Individuals affected by ectodermal dysplasia have abnormalities in different ectodermal structures. Some ectodermal dysplasia types are mild, while others are devastating. Obvious manifestations of the disorders are not clinically apparent in most newborns. Dental, hair, and nail anomalies usually become evident during infancy or childhood. A family history of similar clinical features is helpful.

Other signs and symptoms that may be variably seen include the following:

Physical Examination

Clinical appearance depends on the specific anomalies associated with each disorder. General features may include the following:

Following are several of the well-defined ectodermal dysplasias.

Hypohidrotic ectodermal dysplasia

Hypohidrotic ectodermal dysplasia is characterized by reduced or absent sweating associated with other ectodermal defects.[54]

The typical facies, which is often not recognized until infancy, is characterized by frontal bossing; sunken cheeks; saddle nose; thick, everted lips; wrinkled, hyperpigmented periorbital skin; and large, low-set ears. See the image below.

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Wrinkled, hyperpigmented skin around the eyes and everted lips are typical characteristics of anhidrotic/hypohidrotic ectodermal dysplasia syndrome.

Dental manifestations include conical or pegged teeth, hypodontia or complete anodontia, and delayed eruption of permanent teeth.

Most patients have fine, sparse, lusterless, fair hair; therefore, little pigmentation in the hair shaft is observed microscopically and the medulla is often discontinuous. When medullation is present, a "bar code" appearance is often seen.

Onychodystrophy may occur but is not common. Extensive scaling of the skin and unexplained pyrexia secondary to anhidrosis may occur in the neonatal period. The development of a chronic eczematous dermatitis is common. Other common signs are short stature, eye abnormalities, decreased tearing, and photophobia.

X-linked hypohidrotic ectodermal dysplasia (EDA or Christ-Siemens-Touraine syndrome) is the most common ectodermal dysplasia. Female carriers may display a blaschkoid distribution of hypohidrosis as a result of lyonization and somatic mosaicism for the abnormal X chromosome. Autosomal recessive and autosomal dominant forms of hypohidrotic ectodermal dysplasia have been reported but are rare. Intelligence is normal.

Hidrotic ectodermal dysplasia (Clouston syndrome)

Hidrotic ectodermal dysplasia (Clouston syndrome) is inherited in an autosomal dominant manner; the homozygous state may be lethal. It is more common in persons of French-Canadian ancestry.[55, 56, 57]

Scalp hair is very sparse, fine, and brittle and alopecia is common. Eyebrows are thinned or absent. Nail dystrophy is common. Persistent paronychial infections are frequent. Polydactyly, syndactyly, and bulbous fingertips may be present. Patients have normal facies, no specific dental defects, and normal sweating. Other reported findings include reticulate hyperpigmentation of the knees, elbows, and fingers; palmoplantar keratoderma; and eccrine poromatosis.

Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC or Hay-Wells) syndrome

AEC (Hay-Wells) syndrome is inherited as an autosomal dominant trait of variable expressivity.[58] Scaling and erythema may be present at birth. The characteristic facies is due to ankyloblepharon (congenital adhesion of the upper and lower eyelid margins by fibrous bands); a broad nasal bridge; and a sunken, hypoplastic maxilla. Cleft palate is common; cleft lip is rare.

A recalcitrant, crusted, inflammatory scalp dermatitis may cause scarring alopecia.[59] Chronic blepharitis and conjunctivitis may develop. Nails are absent or dystrophic; pegged teeth are common. Mild hypohidrosis is common. Hair may be sparse and coarse.

Ectrodactyly-ectodermal defects-cleft lip/palate (EEC) syndrome

EEC syndrome is inherited as an autosomal dominant trait of low penetrance and variable expressivity.[60] Many sporadic cases have been reported. Ectrodactyly with tetramelic 3-4 syndactyly results in the characteristic lobster-claw deformity of the hands and feet. Hypoplastic metacarpal or metatarsal bones may be present. Cleft lip and palate create a characteristic nasal contour.

Other ectodermal anomalies include mild hypohidrosis; coarse, dry hair with hypotrichosis; xerostomia; dystrophic nails; dental enamel hypoplasia; and microdontia.

Associated defects include blepharophimosis, lacrimal duct anomalies, strabismus, deafness, choanal atresia, and abnormalities of the genitourinary tract. A rare variant, ectrodactyly-ectodermal defects-clefting with urinary tract abnormalities and thymic abnormalities (EEC/EECUT), has also been associated with T-cell lymphopenia.[61]

Rapp-Hodgkin ectodermal dysplasia

Rapp-Hodgkin ectodermal dysplasia is an autosomal dominant syndrome.[62] High forehead, narrow nose, cleft lip or palate, and maxillary hyperplasia produce a distinctive facies. Hypohidrosis is severe enough to result in heat intolerance. Dental defects include conical teeth and hypodontia. Hair is sparse, has a steel-wool texture, and may show pili torti or pili canaliculi, as shown in the images below. Many patients present with recalcitrant, inflammatory scalp dermatitis followed by scarring alopecia. Nails are narrow and dystrophic, also shown below. Occasional abnormalities include deafness, eye defects, and hypospadias.

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Abnormal hair shaft showing pili torti and a longitudinal groove (pili canaliculi) from a patient with Rapp-Hodgkin syndrome.

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Hands of father and son with Rapp-Hodgkin syndrome. Nails have the same characteristics; they are brittle, thin, and dystrophic.


Patients with severe dental abnormalities or cleft lip and/or palate may develop feeding difficulties, which may result in malnutrition and failure to thrive.

Patients affected by anodontia may show shrinkage of the bone supporting the denture after long-term denture use.

Patients with anhidrosis/hypohidrosis are prone to hyperpyrexia and heat exhaustion.

Patients with chronic scalp dermatitis and erosions often develop recurrent bacterial and fungal skin infections.

Patients with abnormal mucous gland function may develop secondary infections, especially in the upper respiratory tract.

Patients with immunodeficiency are at risk for recurrent viral, bacterial, and fungal infections.

Laboratory Studies

In general, laboratory studies are not useful in the diagnosis or management of the ectodermal dysplasias.

Patients with ectodermal dysplasia associated with immunodeficiency may have hypogammaglobulinemia with impaired lymphocyte proliferation and cell-mediated immunity. An appropriate evaluation, including determination of quantitative immunoglobulin levels and T-cell subset populations, should be performed.

Imaging Studies

Perform orthopantography at an early age if hypodontia or dental abnormalities are present.

X-ray films of hands, feet, or both may demonstrate specific skeletal deformities.

Renal ultrasonography, voiding cystourethrography, and intravenous pyelography may be helpful in evaluating children with ectodermal dysplasia in association with cleft lip and/or palate for underlying genitourinary tract anomalies.

Other Tests

Sweat pore counts, pilocarpine iontophoresis, and skin biopsy may document hypohidrosis and a reduction in the number of eccrine glands.

Sweat pore counts may be performed using yellow starch–iodine powder applied to palmar or dorsal skin. In unaffected persons, sweating turns the yellow starch–iodine powder to deep purple, allowing visualization of sweat pores. Sweat pores are poorly visualized in affected children. Female carriers of X-linked EDA may demonstrate a mosaic pattern of areas of normal numbers of sweat pores alternating with areas of absent pores. Streaky areas of hypohidrosis that follow Blaschko lines are observed upon starch-iodine staining.

For skin biopsy, the hypothenar eminence is the most reliable biopsy site in order to demonstrate an absence or hypoplasia of sweat glands. Fetal skin biopsy may help identify the presence of decreased numbers of eccrine sweat glands for prenatal diagnosis of hypohidrotic ectodermal dysplasia.

Prenatal diagnosis using genetic mutation analysis may be performed for those ectodermal dysplasias in which the genetic mutation is known.

Indirect prenatal diagnosis may be performed by linkage analysis applied to chorionic villus samples at the 10th week of gestation for some ectodermal dysplasias.

Genetic testing for several forms of ectodermal dysplasia, including hidrotic ectodermal dysplasia; X-linked recessive and autosomal dominant hypohidrotic ectodermal dysplasia; EEC syndrome, AEC syndrome, and other related ectodermal dysplasias and WNT10A-associated ectodermal dysplasias is available through GeneDx.

Histologic Findings

Skin histopathology documents a reduction in the number of sweat glands, hair follicles, and sebaceous glands associated with the different ectodermal dysplasias. In EDA, the epidermis is thin and flattened. Eccrine sweat glands are few or poorly developed or are very rudimentary. Beyond the skin, mucous glands in the upper respiratory tract and bronchi are often reduced in number. Salivary glands may show ectasia of ducts and inflammatory changes.

Medical Care

The care of affected patients depends on which ectodermal structures are involved.

For patients with anhidrosis/hypohidrosis, advise air conditioning for home, school, and work. Encourage frequent consumption of cool liquids to maintain adequate hydration and thermoregulation. Finally, advise patients to wear cool clothing.

For patients with dental defects, advise early dental evaluation and intervention and encourage routine dental hygiene. An international consensus meeting of experts in pediatric dentistry, orthodontics, and prosthodontics has published recommendations for the diagnosis, evaluation, and treatment of patients with ectodermal dysplasia, including use of dental implants.[63, 64] Advise orthodontic treatment for cosmetic reasons and to ensure adequate nutritional intake.[65, 66, 67, 68, 69, 70, 71, 72, 73]

Patients with xerosis or eczematous dermatitis may benefit from the use of topical emollients.

Patients with severe alopecia can wear wigs to improve their appearance. Use of topical minoxidil with or without a topical tretinoin has been shown to improve hair growth in a small number of patients.[74, 75]

Patients with scalp erosions should be treated with topical and systemic antibiotics as needed. General scalp care may involve the use of weekly dilute bleach baths or acetic acid soaks to minimize bacterial colonization of the scalp. Application of special scalp dressings may be helpful. The use of high-potency topical corticosteroids has also been reported to be beneficial in the treatment of scalp erosions associated with Rapp-Hodgkin ectodermal dysplasia.[76]

Use artificial tears to prevent damage to the cornea in patients with reduced lacrimation.

Protect nasal mucosa with saline sprays followed by the application of petrolatum.

Patients with ectodermal dysplasia with immunodeficiency should be monitored for infection and treated with therapeutic and/or prophylactic antibiotics when appropriate.

Allogeneic stem cell transplantation has been performed in a small number of patients with autosomal dominant ectodermal dysplasia with immunodeficiency (EDA-ID); poor engraftment and post-transplant complications were common.[77, 78]

Surgical Care

Early repair of cleft lip or palate may lessen facial deformities and improve speech. Other midfacial defects or hand/foot deformities may be surgically corrected in order to improve function and reduce physical disfigurement.


Consultation with the following specialists may be necessary:


No dietary restrictions are indicated.


Instruct patients with hypohidrosis to avoid vigorous physical activities and to maintain adequate hydration. Advise on the importance of light clothing, a cool-water spray bottle, and restriction of overexposure to warm temperatures. Recommend swimming or sedentary sports (eg, archery). Educate parents that antipyretics are not effective in the treatment of hyperpyrexia.


Prenatal intervention for X-linked hypohidrotic ectodermal dysplasia (XLHED) due to EDA mutation has been performed during two pregnancies via intra-amniotic administration of recombinant ectodysplasin; normal sweating was reported in all infants (two twins and a singleton) with no reported manifestations of XLHED noted at age 14 and 22 months.[79]

Medication Summary

At this time, no pharmacological treatment is available.


Kara N Shah, MD, PhD, Associate Professor, Departments of Pediatrics and Dermatology, University of Cincinnati College of Medicine

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Abbvie; Pfizer<br/>Serve(d) as a speaker or a member of a speakers bureau for: Pfizer.

Specialty Editors

Michael J Wells, MD, FAAD, Dermatologic/Mohs Surgeon, The Surgery Center at Plano Dermatology

Disclosure: Nothing to disclose.

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

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Disclosure: Nothing to disclose.

Additional Contributors

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

Disclosure: Nothing to disclose.


The authors and editors of Medscape Reference 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.


  1. Weech AA. Hereditary ectodermal dysplasia (congenital ectodermal defect). Am J Dis Child. 1929. 37:766-90.
  2. Pinheiro M, Freire-Maia N. The ectodermal dysplasias. Arch Dermatol. 1982 Apr. 118(4):215-6. [View Abstract]
  3. Pinheiro M, Freire-Maia N. Ectodermal dysplasias: a clinical classification and a causal review. Am J Med Genet. 1994 Nov 1. 53(2):153-62. [View Abstract]
  4. Freire-Maia N, Lisboa-Costa T, Pagnan NA. Ectodermal dysplasias: how many?. Am J Med Genet. 2001 Nov 15. 104(1):84. [View Abstract]
  5. Visinoni AF, Lisboa-Costa T, Pagnan NA, Chautard-Freire-Maia EA. Ectodermal dysplasias: clinical and molecular review. Am J Med Genet A. 2009 Sep. 149A(9):1980-2002. [View Abstract]
  6. Pagnan NA, Visinoni ÁF. Update on ectodermal dysplasias clinical classification. Am J Med Genet A. 2014 Oct. 164A (10):2415-23. [View Abstract]
  7. Lamartine J. Towards a new classification of ectodermal dysplasias. Clin Exp Dermatol. 2003 Jul. 28(4):351-5. [View Abstract]
  8. Priolo M, Lagana C. Ectodermal dysplasias: a new clinical-genetic classification. J Med Genet. 2001 Sep. 38(9):579-85. [View Abstract]
  9. Itin PH, Fistarol SK. Ectodermal dysplasias. Am J Med Genet C Semin Med Genet. 2004 Nov 15. 131C(1):45-51. [View Abstract]
  10. Okamura E, Suda N, Baba Y, Fukuoka H, Ogawa T, Ohkuma M, et al. Dental and maxillofacial characteristics in six Japanese individuals with ectrodactyly-ectodermal dysplasia-clefting (EEC)syndrome. Cleft Palate Craniofac J. 2012 Jan 11. [View Abstract]
  11. Rouse C, Siegfried E, Breer W, Nahass G. Hair and sweat glands in families with hypohidrotic ectodermal dysplasia: further characterization. Arch Dermatol. 2004 Jul. 140(7):850-5. [View Abstract]
  12. Berg D, Weingold DH, Abson KG, Olsen EA. Sweating in ectodermal dysplasia syndromes. A review. Arch Dermatol. 1990 Aug. 126(8):1075-9. [View Abstract]
  13. Clauss F, Maniere MC, Obry F, et al. Dento-craniofacial phenotypes and underlying molecular mechanisms in hypohidrotic ectodermal dysplasia (HED): a review. J Dent Res. 2008 Dec. 87(12):1089-99. [View Abstract]
  14. Priolo M. Ectodermal dysplasias: an overview and update of clinical and molecular-functional mechanisms. Am J Med Genet A. 2009 Sep. 149A(9):2003-13. [View Abstract]
  15. Kere J, Srivastava AK, Montonen O, et al. X-linked anhidrotic (hypohidrotic) ectodermal dysplasia is caused by mutation in a novel transmembrane protein. Nat Genet. 1996 Aug. 13(4):409-16. [View Abstract]
  16. Monreal AW, Zonana J, Ferguson B. Identification of a new splice form of the EDA1 gene permits detection of nearly all X-linked hypohidrotic ectodermal dysplasia mutations [published erratum appears in Am J Hum Genet 1998 Oct;63(4):1253-5]. Am J Hum Genet. 1998 Aug. 63(2):380-9. [View Abstract]
  17. Jones KB, Goodwin AF, Landan M, Seidel K, Tran DK, Hogue J, et al. Characterization of X-linked hypohidrotic ectodermal dysplasia (XL-HED) hair and sweat gland phenotypes using phototrichogram analysis and live confocal imaging. Am J Med Genet A. 2013 Jul. 161A(7):1585-93. [View Abstract]
  18. Monreal AW, Ferguson BM, Headon DJ, Street SL, Overbeek PA, Zonana J. Mutations in the human homologue of mouse dl cause autosomal recessive and dominant hypohidrotic ectodermal dysplasia. Nat Genet. 1999 Aug. 22(4):366-9. [View Abstract]
  19. Wisniewski SA, Trzeciak WH. A rare heterozygous TRAF6 variant is associated with hypohidrotic ectodermal dysplasia. Br J Dermatol. 2012 Jun. 166(6):1353-6. [View Abstract]
  20. Lamartine J, Munhoz Essenfelder G, Kibar Z, et al. Mutations in GJB6 cause hidrotic ectodermal dysplasia. Nat Genet. 2000 Oct. 26(2):142-4. [View Abstract]
  21. Courtois G, Smahi A, Reichenbach J, et al. A hypermorphic IkappaBalpha mutation is associated with autosomal dominant anhidrotic ectodermal dysplasia and T cell immunodeficiency. J Clin Invest. 2003 Oct. 112(7):1108-15. [View Abstract]
  22. Doffinger R, Smahi A, Bessia C, et al. X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-kappaB signaling. Nat Genet. 2001 Mar. 27(3):277-85. [View Abstract]
  23. Zonana J, Elder ME, Schneider LC, et al. A novel X-linked disorder of immune deficiency and hypohidrotic ectodermal dysplasia is allelic to incontinentia pigmenti and due to mutations in IKK-gamma (NEMO). Am J Hum Genet. 2000 Dec. 67(6):1555-62. [View Abstract]
  24. Rinne T, Brunner HG, van Bokhoven H. p63-associated disorders. Cell Cycle. 2007 Feb 1. 6(3):262-8. [View Abstract]
  25. Rinne T, Hamel B, van Bokhoven H, Brunner HG. Pattern of p63 mutations and their phenotypes--update. Am J Med Genet A. 2006 Jul 1. 140(13):1396-406. [View Abstract]
  26. Richard G, Rouan F, Willoughby CE, et al. Missense mutations in GJB2 encoding connexin-26 cause the ectodermal dysplasia keratitis-ichthyosis-deafness syndrome. Am J Hum Genet. 2002 May. 70(5):1341-8. [View Abstract]
  27. Suzuki K, Hu D, Bustos T, et al. Mutations of PVRL1, encoding a cell-cell adhesion molecule/herpesvirus receptor, in cleft lip/palate-ectodermal dysplasia. Nat Genet. 2000 Aug. 25(4):427-30. [View Abstract]
  28. McGrath JA, McMillan JR, Shemanko CS, et al. Mutations in the plakophilin 1 gene result in ectodermal dysplasia/skin fragility syndrome. Nat Genet. 1997 Oct. 17(2):240-4. [View Abstract]
  29. Wang X, Reid Sutton V, Omar Peraza-Llanes J, et al. Mutations in X-linked PORCN, a putative regulator of Wnt signaling, cause focal dermal hypoplasia. Nat Genet. 2007 Jul. 39(7):836-8. [View Abstract]
  30. Lugassy J, Itin P, Ishida-Yamamoto A, et al. Naegeli-Franceschetti-Jadassohn syndrome and dermatopathia pigmentosa reticularis: two allelic ectodermal dysplasias caused by dominant mutations in KRT14. Am J Hum Genet. 2006 Oct. 79(4):724-30. [View Abstract]
  31. Shah S, Boen M, Kenner-Bell B, Schwartz M, Rademaker A, Paller AS. Pachyonychia congenita in pediatric patients: natural history, features, and impact. JAMA Dermatol. 2014 Feb. 150 (2):146-53. [View Abstract]
  32. Wilson NJ, O'Toole EA, Milstone LM, Hansen CD, Shepherd AA, Al-Asadi E, et al. The molecular genetic analysis of the expanding pachyonychia congenita case collection. Br J Dermatol. 2014 Aug. 171 (2):343-55. [View Abstract]
  33. McLean WH, Hansen CD, Eliason MJ, Smith FJ. The phenotypic and molecular genetic features of pachyonychia congenita. J Invest Dermatol. 2011 May. 131 (5):1015-7. [View Abstract]
  34. Galdzicka M, Patnala S, Hirshman MG, et al. A new gene, EVC2, is mutated in Ellis-van Creveld syndrome. Mol Genet Metab. 2002 Dec. 77(4):291-5. [View Abstract]
  35. Ruiz-Perez VL, Ide SE, Strom TM, et al. Mutations in a new gene in Ellis-van Creveld syndrome and Weyers acrodental dysostosis. Nat Genet. 2000 Mar. 24(3):283-6. [View Abstract]
  36. Ruiz-Perez VL, Tompson SW, Blair HJ, et al. Mutations in two nonhomologous genes in a head-to-head configuration cause Ellis-van Creveld syndrome. Am J Hum Genet. 2003 Mar. 72(3):728-32. [View Abstract]
  37. Ali RH, Habib R, Ud-Din N, Khan MN, Ansar M, Ahmad W. Novel mutations in the gene HOXC13 underlying pure hair and nail ectodermal dysplasia in consanguineous families. Br J Dermatol. 2013 Aug. 169(2):478-80. [View Abstract]
  38. Naeem M, Wajid M, Lee K, Leal SM, Ahmad W. A mutation in the hair matrix and cuticle keratin KRTHB5 gene causes ectodermal dysplasia of hair and nail type. J Med Genet. 2006 Mar. 43(3):274-9. [View Abstract]
  39. Shimomura Y, Wajid M, Kurban M, Sato N, Christiano AM. Mutations in the keratin 85 (KRT85/hHb5) gene underlie pure hair and nail ectodermal dysplasia. J Invest Dermatol. 2010 Mar. 130(3):892-5. [View Abstract]
  40. Smahi A, Courtois G, Vabres P, Yamaoka S, Heuertz S, Munnich A, et al. Genomic rearrangement in NEMO impairs NF-kappaB activation and is a cause of incontinentia pigmenti. The International Incontinentia Pigmenti (IP) Consortium. Nature. 2000 May 25. 405(6785):466-72. [View Abstract]
  41. Lian J, Cuk M, Kahlfuss S, Kozhaya L, Vaeth M, Rieux-Laucat F, et al. ORAI1 mutations abolishing store-operated Ca2+ entry cause anhidrotic ectodermal dysplasia with immunodeficiency. J Allergy Clin Immunol. 2018 Oct. 142 (4):1297-1310.e11. [View Abstract]
  42. Bohring A, Stamm T, Spaich C, Haase C, Spree K, Hehr U, et al. WNT10A mutations are a frequent cause of a broad spectrum of ectodermal dysplasias with sex-biased manifestation pattern in heterozygotes. Am J Hum Genet. 2009 Jul. 85(1):97-105. [View Abstract]
  43. Adaimy L, Chouery E, Megarbane H, Mroueh S, Delague V, Nicolas E, et al. Mutation in WNT10A is associated with an autosomal recessive ectodermal dysplasia: the odonto-onycho-dermal dysplasia. Am J Hum Genet. 2007 Oct. 81(4):821-8. [View Abstract]
  44. Mues G, Bonds J, Xiang L, Vieira AR, Seymen F, Klein O, et al. The WNT10A gene in ectodermal dysplasias and selective tooth agenesis. Am J Med Genet A. 2014 Oct. 164A (10):2455-60. [View Abstract]
  45. Tziotzios C, Petrof G, Liu L, Verma A, Wedgeworth EK, Mellerio JE, et al. Clinical features and WNT10A mutations in seven unrelated cases of Schöpf-Schulz-Passarge syndrome. Br J Dermatol. 2014 Nov. 171 (5):1211-4. [View Abstract]
  46. Motil KJ, Fete TJ, Fraley JK, et al. Growth characteristics of children with ectodermal dysplasia syndromes. Pediatrics. 2005 Aug. 116(2):e229-34. [View Abstract]
  47. Kaercher T. Ocular symptoms and signs in patients with ectodermal dysplasia syndromes. Graefes Arch Clin Exp Ophthalmol. 2004 Jun. 242(6):495-500. [View Abstract]
  48. Nordgarden H, Storhaug K, Lyngstadaas SP, Jensen JL. Salivary gland function in persons with ectodermal dysplasias. Eur J Oral Sci. 2003 Oct. 111(5):371-6. [View Abstract]
  49. Dietz J, Kaercher T, Schneider AT, Zimmermann T, Huttner K, Johnson R, et al. Early respiratory and ocular involvement in X-linked hypohidrotic ectodermal dysplasia. Eur J Pediatr. 2013 Aug. 172(8):1023-31. [View Abstract]
  50. Daniel E, McCurdy EA, Shashi V, McGuirt WF Jr. Ectodermal dysplasia: otolaryngologic manifestations and management. Laryngoscope. 2002 Jun. 112(6):962-7. [View Abstract]
  51. Mehta U, Brunworth J, Lewis RA, Sindwani R. Rhinologic manifestations of ectodermal dysplasia. Am J Rhinol. 2007 Jan-Feb. 21(1):55-8. [View Abstract]
  52. Callea M, Teggi R, Yavuz I, Tadini G, Priolo M, Crovella S, et al. Ear nose throat manifestations in hypoidrotic ectodermal dysplasia. Int J Pediatr Otorhinolaryngol. 2013 Nov. 77(11):1801-4. [View Abstract]
  53. Bergendal B. Orodental manifestations in ectodermal dysplasia-a review. Am J Med Genet A. 2014 Oct. 164A (10):2465-71. [View Abstract]
  54. Fete M, Hermann J, Behrens J, Huttner KM. X-linked hypohidrotic ectodermal dysplasia (XLHED): clinical and diagnostic insights from an international patient registry. Am J Med Genet A. 2014 Oct. 164A (10):2437-42. [View Abstract]
  55. Clouston HR. A hereditary ectodermal dystrophy. Can Med Assoc J. 1929. 21:18-31.
  56. Pierard GE, Van Neste D, Letot B. Hidrotic ectodermal dysplasia. Dermatologica. 1979. 158(3):168-74. [View Abstract]
  57. Reynold JM, Gold MB, Scriver CR. The characterization of hereditary abnormalities of keratin: Clouston's ectodermal dysplasia. Birth Defects Orig Artic Ser. 1971 Jun. 7(8):91-5. [View Abstract]
  58. Hay RJ, Wells RS. The syndrome of ankyloblepharon, ectodermal defects and cleft lip and palate: an autosomal dominant condition. Br J Dermatol. 1976 Mar. 94(3):277-89. [View Abstract]
  59. Fosko SW, Stenn KS, Bolognia JL. Ectodermal dysplasias associated with clefting: significance of scalp dermatitis. J Am Acad Dermatol. 1992 Aug. 27(2 Pt 1):249-56. [View Abstract]
  60. Roelfsema NM, Cobben JM. The EEC syndrome: a literature study. Clin Dysmorphol. 1996 Apr. 5(2):115-27. [View Abstract]
  61. Giampietro PF, Baker MW, Basehore MJ, Jones JR, Seroogy CM. Novel mutation in TP63 associated with ectrodactyly ectodermal dysplasia and clefting syndrome and T cell lymphopenia. Am J Med Genet A. 2013 Jun. 161A(6):1432-5. [View Abstract]
  62. Felding IB, Bjorklund LJ. Rapp-Hodgkin ectodermal dysplasia. Pediatr Dermatol. 1990 Jun. 7(2):126-31. [View Abstract]
  63. Klineberg I, Cameron A, Hobkirk J, Bergendal B, Maniere MC, King N, et al. Rehabilitation of children with ectodermal dysplasia. Part 2: an international consensus meeting. Int J Oral Maxillofac Implants. 2013 Jul-Aug. 28(4):1101-9. [View Abstract]
  64. Klineberg I, Cameron A, Whittle T, Hobkirk J, Bergendal B, Maniere MC, et al. Rehabilitation of children with ectodermal dysplasia. Part 1: an international Delphi study. Int J Oral Maxillofac Implants. 2013 Jul-Aug. 28(4):1090-100. [View Abstract]
  65. Hickey AJ, Vergo TJ. Prosthetic treatments for patients with ectodermal dysplasia. J Prosthet Dent. 2001 Oct. 86(4):364-8. [View Abstract]
  66. Imirzalioglu P, Uckan S, Haydar SG. Surgical and prosthodontic treatment alternatives for children and adolescents with ectodermal dysplasia: a clinical report. J Prosthet Dent. 2002 Dec. 88(6):569-72. [View Abstract]
  67. Dhanrajani PJ, Jiffry AO. Management of ectodermal dysplasia: a literature review. Dent Update. 1998 Mar. 25(2):73-5. [View Abstract]
  68. Lypka M, Yarmand D, Burstein J, Tso V, Yamashita DD. Dental implant reconstruction in a patient with ectodermal dysplasia using multiple bone grafting techniques. J Oral Maxillofac Surg. 2008 Jun. 66(6):1241-4. [View Abstract]
  69. Tarjan I, Gabris K, Rozsa N. Early prosthetic treatment of patients with ectodermal dysplasia: a clinical report. J Prosthet Dent. 2005 May. 93(5):419-24. [View Abstract]
  70. Al-Ibrahim HA, Al-Hadlaq SM, Abduljabbar TS, Al-Hamdan KS, Abdin HA. Surgical and implant-supported fixed prosthetic treatment of a patient with ectodermal dysplasia: a case report. Spec Care Dentist. 2012 Jan. 32(1):1-5. [View Abstract]
  71. El Osta Chaiban R, Chaiban W. Ectodermal dysplasia: dental management and benefits, a case report. Eur J Paediatr Dent. 2011 Dec. 12(4):282-4. [View Abstract]
  72. Aydinbelge M, Gumus HO, Sekerci AE, Demetoglu U, Etoz OA. Implants in children with hypohidrotic ectodermal dysplasia: an alternative approach to esthetic management: case report and review of the literature. Pediatr Dent. 2013 Sep-Oct. 35(5):441-6. [View Abstract]
  73. Dhima M, Salinas TJ, Cofer SA, Rieck KL. Rehabilitation of medically complex ectodermal dysplasia with novel surgical and prosthodontic protocols. Int J Oral Maxillofac Surg. 2013 Sep 12. [View Abstract]
  74. Lee HE, Chang IK, Im M, Seo YJ, Lee JH, Lee Y. Topical minoxidil treatment for congenital alopecia in hypohidrotic ectodermal dysplasia. J Am Acad Dermatol. 2013 Apr. 68(4):e139-40. [View Abstract]
  75. Melkote S, Dhurat RS, Palav A, Jerajani HR. Alopecia in congenital hidrotic ectodermal dysplasia responding to treatment with a combination of topical minoxidil and tretinoin. Int J Dermatol. 2009 Feb. 48(2):184-5. [View Abstract]
  76. Theiler M, Frieden IJ. High-Potency Topical Steroids: An Effective Therapy for Chronic Scalp Inflammation in Rapp-Hodgkin Ectodermal Dysplasia. Pediatr Dermatol. 2016 Mar-Apr. 33 (2):e84-7. [View Abstract]
  77. Dupuis-Girod S, Cancrini C, Le Deist F, et al. Successful allogeneic hemopoietic stem cell transplantation in a child who had anhidrotic ectodermal dysplasia with immunodeficiency. Pediatrics. 2006 Jul. 118(1):e205-11. [View Abstract]
  78. Fish JD, Duerst RE, Gelfand EW, Orange JS, Bunin N. Challenges in the use of allogeneic hematopoietic SCT for ectodermal dysplasia with immune deficiency. Bone Marrow Transplant. 2008 Sep 15. [View Abstract]
  79. Schneider H, Faschingbauer F, Schuepbach-Mallepell S, Körber I, Wohlfart S, Dick A, et al. Prenatal Correction of X-Linked Hypohidrotic Ectodermal Dysplasia. N Engl J Med. 2018 Apr 26. 378 (17):1604-1610. [View Abstract]

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

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.

Typical cleft lip/palate and maxillary hyperplasia in a patient with Rapp-Hodgkin syndrome.

Wrinkled, hyperpigmented skin around the eyes and everted lips are typical characteristics of anhidrotic/hypohidrotic ectodermal dysplasia 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.

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.