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Hypohidrotic Ectodermal Dysplasia

Synonyms: Anhidrotic Ectodermal Dysplasia, Christ-Siemens-Touraine Syndrome

, DDS, MS, , MD, and , MSN, RN, CCM.

Author Information

Initial Posting: ; Last Update: June 1, 2017.

Summary

Clinical characteristics.

Hypohidrotic ectodermal dysplasia (HED) is characterized by hypotrichosis (sparseness of scalp and body hair), hypohidrosis (reduced ability to sweat), and hypodontia (congenital absence of teeth).

The cardinal features of classic HED become obvious during childhood. The scalp hair is thin, lightly pigmented, and slow-growing. Sweating, although present, is greatly deficient, leading to episodes of hyperthermia until the affected individual or family acquires experience with environmental modifications to control temperature. Only a few abnormally formed teeth erupt, and at a later-than-average age. Physical growth and psychomotor development are otherwise within normal limits.

Mild HED is characterized by mild manifestations of any or all the characteristic features.

Diagnosis/testing.

Classic HED can be diagnosed after infancy on the basis of physical features in most affected individuals. Identification of a hemizygous EDA pathogenic variant in an affected male or biallelic EDAR, EDARADD, or WNT10A pathogenic variants in an affected male or female confirms the diagnosis.

The diagnosis of mild HED is established in a female by identification of a heterozygous EDA, EDAR, EDARADD, or WNT10A pathogenic variant. The diagnosis of mild HED is established in a male by identification of a heterozygous EDAR, EDARADD, or WNT10A pathogenic variant.

Management.

Treatment of manifestations: Wigs or special hair care formulas for sparse, dry hair may be useful. Access to an adequate water supply and a cool environment during hot weather. Early dental treatment; bonding of conical shaped teeth; orthodontics as necessary; dental implants in the anterior portion of the mandibular arch in older children; replacement of dental prostheses as needed, often every 2.5 years; dental implants in adults; therapeutics to maintain oral lubrication and control caries; dietary counseling for individuals with chewing and swallowing difficulties. Nasal and aural concretions may be removed with suction devices or forceps as needed by an otolaryngologist. Prevention of nasal concretions through humidification of ambient air is helpful. Skin care products for eczema and exposures that exacerbate dry skin.

Prevention of secondary complications: Saliva substitutes and optimal fluoride exposure may be helpful in preventing dental caries in those individuals having a marked reduction in salivary flow.

Surveillance: Dental evaluation by age one year with follow-up dental evaluations every six to 12 months.

Agents/circumstances to avoid: Exposure to extreme heat.

Evaluation of relatives at risk: If the family-specific pathogenic variant(s) are known, molecular genetic testing of at-risk relatives should be offered to permit early diagnosis and treatment, especially to avoid hyperthermia.

Genetic counseling.

HED is inherited in an autosomal dominant, autosomal recessive, or X-linked manner. The majority of individuals with HED have the X-linked form. The mode of inheritance may be determined in some instances by family history and in others by molecular genetic testing. Carrier testing is possible for the X-linked and autosomal recessive forms if the pathogenic variant(s) in the family are known. Prenatal testing is possible for pregnancies at increased risk for all forms if the pathogenic variant(s) in the family are known.

GeneReview Scope

Hypohidrotic Ectodermal Dysplasia: Included Phenotypes
  • Classic hypohidrotic ectodermal dysplasia
  • Mild hypohidrotic ectodermal dysplasia

For synonyms and outdated names see Nomenclature.

Diagnosis

No guidelines regarding diagnostic criteria for hypohidrotic ectodermal dysplasia have been developed.

Suggestive Findings

Hypohidrotic ectodermal dysplasia (HED) should be suspected in an individual with:

  • Hypotrichosis (sparseness of scalp and body hair). Scalp hair has thin shafts and is lightly pigmented. Note: Hair shafts can be brittle and twisted (pili torti) or have other anomalies on microscopic analysis; however, these findings are not sufficiently sensitive to be of diagnostic benefit [Rouse et al 2004]. Secondary sexual hair (beard; axillary and pubic hair) can be normal.
  • Hypohidrosis (reduced ability to sweat). Reduced ability to sweat in response to heat leads to hyperthermia:
    • The function of sweat glands may be assessed by bringing the skin into contact with an iodine solution and raising ambient temperatures to induce sweating. The iodine solution turns color when exposed to sweat and can be used to determine the amount and location of sweating.
    • The number and distribution of sweat pores can be determined by coating parts of the body (usually the hypothenar eminences of the palms) with impression materials commonly used by dentists.
    • While skin biopsies have been used to determine the distribution and morphology of sweat glands, noninvasive techniques are equally effective. Live confocal microscope imaging is able to visualize the sweat ducts on the palms [Jones et al 2013].
  • Hypodontia (congenital absence of teeth):
    • An average of nine permanent teeth – typically the canines and first molars –develop in individuals with classic HED [Lexner et al 2007].
    • Teeth are often smaller than average and have an altered morphology; the anterior teeth frequently have conical crowns.
    • Dental radiographs are helpful for determining the extent of hypodontia and are useful in the diagnosis of mildly affected individuals. Taurodontism (elongation of the pulp chamber) is more common in molar teeth of individuals with HED than in unaffected individuals.

Note: Anthropometric variations (measurements of facial form and tooth size) in HED are subtle and have not proven clinically useful.

Carrier detection for X-linked HED

  • Because females with X-linked HED show mosaic patterns of sweat pore function and distribution, use of an iodine solution to assess sweat gland function or impression materials to assess number and distribution of sweat pores is particularly useful.
  • Between 60% and 80% of females with X-linked HED display some degree of hypodontia [Cambiaghi et al 2000].

Establishing the Diagnosis

Classic HED is often diagnosed after infancy in affected individuals with the above characteristic features of hypotrichosis, hypohidrosis, and hypodontia.

Mild HED

  • Male proband. The diagnosis of mild HED can be established in a male proband with the mild manifestations of the cardinal features. Identification of a heterozygous EDAR, EDARADD, or WNT10A pathogenic variant confirms the diagnosis.
  • Female proband. The diagnosis of mild HED due to an EDA pathogenic variant can be established in a female proband with a mosaic pattern of sweat pore function and distribution, hypodontia, and a family history suggestive of X-linked HED. Identification of a heterozygous EDA pathogenic variant by molecular genetic testing confirms this diagnosis. The diagnosis of mild HED can also be established in a female with mild manifestations by identification of a heterozygous pathogenic variant in EDAR, EDARADD, or WNT10A.

Molecular testing approaches can include serial single-gene testing and a multigene panel.

Serial single-gene testing can be considered if:

If molecular genetic testing of EDA, EDAR, EDARADD, and WNT10A do not identify a pathogenic variant, other forms of ectodermal dysplasia should be considered (see Differential Diagnosis).

A multigene panel that includes EDA, EDAR, EDARADD, WNT10A, and other genes of interest (see Differential Diagnosis) may also be considered. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.

For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.

Table 1.

Molecular Genetic Testing Used in Hypohidrotic Ectodermal Dysplasia

Gene 1MOIProportion of HED Attributed to Pathogenic Variants in This GeneProportion of Pathogenic Variants 2 Detectable by This Method
Sequence analysis 3, 4, 5Gene-targeted deletion/duplication analysis 6
EDAXL~65%-75%~85%-90% 7~10%-15% 7
EDARAD, AR~10%-15%>99% 8See footnote 9
EDARADDAD, AR1%-2% 108/8 11None reported 12
WNT10AAR5%-6% 13~100%None reported
Unknown 14~10%NA
1.
2.

See Molecular Genetics for information on allelic variants detected in this gene.

3.

Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.

4.

Lack of amplification by PCR prior to sequence analysis can suggest a putative (multi)exon or whole-gene deletion on the X chromosome in affected males; confirmation requires additional testing by gene-targeted deletion/duplication analysis.

5.

Sequence analysis of genomic DNA cannot detect a (multi)exon or whole-gene deletion on an X chromosome of carrier females.

6.

Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods that may be used include: quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.

7.
8.
9.

A deletion of at least exon 4 was detected in one individual [Monreal et al 1999].

10.
11.
12.

No deletions or duplications involving EDARADD as causative of HED have been reported.

13.
14.

A novel disease gene mapped to a 5-cM interval at 14q12-q13.1 in one large family with AD HED/EDA, NFKBIA was excluded by sequence analysis [Cluzeau et al 2011].

Clinical Characteristics

Clinical Description

Classic HED

Males with X-linked hypohidrotic ectodermal dysplasia (XLHED) and males and females with autosomal recessive hypohidrotic ectodermal dysplasia (ARHED) caused by EDAR or EDARADD pathogenic variants have the classic form of hypohidrotic ectodermal dysplasia (HED).

Neonates with HED may be diagnosed because of peeling skin, like that of "post-mature" babies, and periorbital hyperpigmentation. In infancy, they may be irritable because of heat intolerance; elevated body temperatures are not uncommon. More often, diagnosis is delayed until the teeth fail to erupt at the expected age (6-9 months) or the teeth that erupt are conical in shape. By this age, affected individuals may have chronic eczema and the periorbital skin may appear wrinkled.

The cardinal features of HED become obvious during childhood:

  • Hypotrichosis. Thin, lightly pigmented, and slow-growing scalp hair. The apparent slow growth of the scalp hair may result from the excessive fragility of the shafts, which break easily with the usual wear and tear of childhood.
  • Hypohidrosis. Greatly reduced sweat function leading to episodes of hyperthermia until the affected individual or family acquires experience with environmental modifications to control temperature [Blüschke et al 2010, Schneider et al 2011]
  • Hypodontia. Later-than-average appearance of only a few teeth, which are abnormally formed [Lexner et al 2008]

Other signs of classic HED include the following:

  • Asymmetric development of the alveolar ridge
  • Changes in nasal secretions from concretions (solidified secretions in the nasal and aural passages) in early infancy to large mucous clots thereafter
  • Depressed nasal bridge that is obvious by early childhood
  • Decreased sebaceous secretions
  • Dry eye symptoms due to abnormal meibomian glands [Dietz et al 2013]
  • Fragile-appearing skin
  • Lack of dermal ridges
  • Periorbital hyperpigmentation that persists
  • Recurrent pneumonia and asthma-like symptoms related to abnormal bronchial glands [Dietz et al 2013]
  • Raspy voice
  • Midface hypoplasia

Physical growth and psychomotor development are otherwise within normal limits.

Mild HED

Females with XLHED and males and females with autosomal dominant HED (ADHED) typically have mild HED.

Females with XLHED may exhibit mild manifestations of any or all the cardinal features: some sparseness of the hair, patchy distribution of sweat dysfunction, and a few small or missing teeth. They may also notice deficient milk production during nursing or have underdeveloped nipples.

Individuals with ADHED exhibit mild manifestations as described for females with XLHED, without the patchy distribution of sweat dysfunction.

WNT10A-Related HED

Variable phenotypes are reported in individuals with pathogenic variants in WNT10A. Individuals may present with severe manifestations consistent with odonto-onycho-dermal dysplasia [Krøigård et al 2016]. WNT10A pathogenic variants may also be found in individuals with mild HED and abnormal dentition. Individuals with WNT10A variants are more likely than those with other forms of HED to have missing fingernails and toenails at birth. Also unlike other forms of HED, the deciduous dentition may be almost completely present but with abnormally shaped teeth, while there is often severe hypodontia of the adult dentition. There may be hyperhidrosis involving the palms and soles with decreased sweating on the rest of the body.

Genotype-Phenotype Correlations

EDA. Phenotypes resulting from EDA pathogenic variants range from classic HED to nonsyndromic hypodontia. Recent investigations suggest that most EDA pathogenic variants associated with nonsyndromic hypodontia are missense variants with most located in the region encoding the tumor necrosis factor domain. Many pathogenic variants associated with X-linked HED are thought to be loss-of-function variants including nonsense variants, insertions, and deletions that span the gene [Zhang et al 2011].

EDAR. Variable phenotypes that range from mild to severe are associated with EDAR pathogenic variants, but genotype-phenotype correlations remain limited [Chassaing et al 2006]. The association of EDAR pathogenic variants and HED features along with the additional findings of amastia and palmoplantar hyperkeratosis has been reported twice, once with a novel homozygous NM_022336.3: c.803+1G>A (IVS9+1G>A) variant [Mégarbané et al 2008] and once with a novel homozygous missense variant NM_022336.3: c.338G>A (p.Cys113Tyr) [Haghighi et al 2013].

WNT10A. Variable phenotypes are reported in individuals with pathogenic variants in WNT10A. Homozygosity for the common c.321C>A (p.Cys107Ter) nonsense variant may be identified more frequently in individuals with severe manifestations, including odonto-onycho-dermal dysplasia [Krøigård et al 2016]. WNT10A pathogenic variants may also be found in individuals with abnormal dentition in association with additional mild ectodermal symptoms or with selective tooth agenesis [Mues et al 2014, Bergendal et al 2016]. Individuals with WNT10A variants are more likely than those with other forms of HED to have missing fingernails and toenails at birth. Also unlike other forms of HED, the deciduous dentition may be almost completely present but with abnormally shaped teeth, while there is often severe hypodontia of the adult dentition. There may be hyperhidrosis involving the palms and soles with decreased sweating on the rest of the body.

Nomenclature

Historically, the term "anhidrotic" has been defined as the inability to perspire; "hypohidrotic" suggests impairment in the ability to perspire. Because most individuals with HED have at least a limited ability to perspire, the term "hypohidrotic" more accurately reflects the condition.

Prevalence

Although not specifically known, it is estimated that at least one in 5,000-10,000 newborns has HED. This is probably an underestimate of the prevalence, as many individuals may be missed during infancy before the cardinal features become obvious.

Affected individuals from all racial and ethnic groups have been reported [Fete et al 2014].

Differential Diagnosis

Numerous types of ectodermal dysplasia exist. Hypodontia with a vague history of heat intolerance or slight sparseness of the hair is a particularly common and troublesome differential diagnosis [Ho et al 1998].

The presence of onychodysplasia (inherent abnormalities of nail development) and other developmental abnormalities favor diagnoses other than hypohidrotic ectodermal dysplasia (HED).

Other types of ectodermal dysplasia that need to be considered include the following:

Management

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with hypohidrotic ectodermal dysplasia (HED), the following evaluations are recommended:

  • Initial evaluation of the developing dentition, typically accomplished by palpating the dental alveolus of the infant/toddler to establish if developing tooth buds (which manifest as bulges in alveolus) are present. A dental evaluation by age one year is recommended.
  • Dental radiographs, essential to determining the extent of hypodontia and frequently taken in the toddler or child using panoramic or conventional dental radiographic techniques
  • Consultation with a clinical geneticist and/or genetic counselor

Treatment of Manifestations

Management of affected individuals targets the three cardinal features and is directed at optimizing psychosocial development, establishing optimal oral function, and preventing hyperthermia.

Hypotrichosis. Wigs or special hair care formulas and techniques to manage sparse, dry hair may be useful. One report describes a child with HED and alopecia who was treated with topical minoxidil to the scalp and had resultant hair growth [Lee et al 2013].

Hypohidrosis. During hot weather, affected individuals must have access to an adequate supply of water and a cool environment, which may mean air conditioning, a wet T-shirt, and/or a spray bottle of water. Some individuals may benefit from "cooling vests."

Affected individuals learn to control their exposure to heat and to minimize its consequences, but special situations may arise in which intervention by physicians and families is helpful. For example, a physician may have to prescribe an air conditioner before a school district complies, or parents may have to advocate for children who need to carry liquids into areas where they are prohibited.

Hypodontia

  • Dental treatment, ranging from simple restorations to dentures, must begin at an early age. Bonding of conical shaped teeth in young affected individuals improves aesthetics and chewing ability.
  • Orthodontics may be necessary.
  • Dental implants in the anterior portion of the mandibular arch have proven successful only in children age seven years and older [Kramer et al 2007, Stanford et al 2008].
  • Children with HED typically need to have their dental prostheses replaced every 2.5 years.
  • Dental implants in adults can support aesthetic and functional dentition.
  • Hyposalivation is present in some individuals, predisposing them to dental caries and the need for therapeutics directed at maintaining oral lubrication and caries control.
  • Dietary counseling may be helpful for those individuals who have trouble chewing and swallowing despite adequate dental care.

Other

  • Regular visits with an ENT physician may be necessary for management of the nasal and aural concretions. Commonly, nasal and aural concretions must be removed with suction devices or forceps and recommendations made about humidification of the ambient air to prevent their formation [Mehta et al 2007].
  • Skin care products are useful for management of eczema and rashes and for dry skin associated with certain outdoor exposures like swimming.
  • Lubrication eye drops can be helpful for dry eyes.

Prevention of Secondary Complications

Saliva substitutes and optimal fluoride exposure may be helpful in preventing dental caries in those individuals having a marked reduction in salivary flow. Other dental caries preventive approaches such as pit and fissure sealants can be beneficial as well.

Surveillance

The first dental visit should occur by age one year to monitor tooth and maxillary/mandibular development and for anticipatory guidance for parents. The developing dentition should be evaluated every six to 12 months to monitor existing treatments and to provide continued interventions as needed.

Agents/Circumstances to Avoid

Individuals with severe hypohidrosis can have marked heat intolerance; care should be taken to prevent exposure to extreme heat and the potential for febrile seizures.

Evaluation of Relatives at Risk

It is appropriate to evaluate apparently asymptomatic, at-risk relatives of an affected individual in order to identify as early as possible those who would benefit from early diagnosis and treatment and, importantly, measures to avoid hyperthermia.

Evaluations can include:

  • Molecular genetic testing if the pathogenic variant(s) in the family are known;
  • Targeted history, physical examination, and dental examination for the features of HED if the pathogenic variant(s) in the family are not known. A sweat test can be done in at-risk relatives of an individual with XLHED.

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Pregnancy Management

Optimal prenatal nutrition is recommended for mothers who are carriers of or affected with HED. Affected women at risk for hyperthermia should take extra care not to become overheated during pregnancy. There are no other special recommendations for pregnancy management.

Some women may have difficulty breastfeeding their infants because of hypoplasia of the mammary glands.

Therapies Under Investigation

A Phase II clinical trial was conducted at several US and European medical centers to investigate the use of EDI200, developed by Edimer Pharmaceuticals, Inc [Huttner 2014]. The results of the study were inconclusive. EDI200 is an ectodysplasin-A1 (EDA-A1) replacement protein that has been shown to bind specifically to the EDA-A1 receptor (EDAR) and activate the signaling pathway that leads to normal ectodermal development. EDI200 has demonstrated permanent correction of the disease manifestations in both mouse and dog models of X-linked hypohidrotic ectodermal dysplasia, with reduction in mortality and morbidity [Huttner 2014]. For additional information on the clinical trial click here

Search ClinicalTrials.gov in the US and www.ClinicalTrialsRegister.eu in Europe for access to information on clinical studies for a wide range of diseases and conditions.

Genetic Counseling

Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members. This section is not meant to address all personal, cultural, or ethical issues that individuals may face or to substitute for consultation with a genetics professional. —ED.

Mode of Inheritance

Hypohidrotic ectodermal dysplasia (HED) is inherited in an autosomal dominant, autosomal recessive, or X-linked manner.

Evaluation of the proband includes review of family history and examination of family members to identify clinical manifestations of hypohidrotic ectodermal dysplasia (HED). The mode of inheritance may be determined by family history and/or molecular genetic testing.

Risk to Family Members – X-Linked Hypohidrotic Ectodermal Dysplasia (XLHED)

Parents of a male proband

  • The father of an affected male will not have the disorder nor will he be hemizygous for the EDA pathogenic variant; therefore, he does not require further evaluation/testing.
  • In a family with more than one affected individual, the mother of an affected male is an obligate heterozygote. Note: If a woman has more than one affected child and no other affected relatives and if the EDA pathogenic variant cannot be detected in her leukocyte DNA, she has germline mosaicism.
  • Clinical examination may detect minimal manifestations of XLHED in the mother (see Mild HED). Molecular genetic testing of the mother is indicated.
  • If a male is the only affected family member (i.e., a simplex case), the mother may be a heterozygote or the affected male may have a de novo EDA pathogenic variant, in which case the mother is not a heterozygote.

Parents of a female proband

  • A female proband may have inherited the EDA pathogenic variant from her father (who may be affected) or her mother (who may be mildly affected) or the pathogenic variant may be de novo.
  • Clinical examination may clarify the status of the parents. Molecular genetic testing is indicated.

Sibs of a male proband. The risk to sibs depends on the genetic status of the mother:

  • If the mother is heterozygous for an EDA pathogenic variant, the chance of transmitting it in each pregnancy is 50%. Male sibs who inherit the pathogenic variant will be affected; female sibs who inherit the pathogenic variant will be heterozygous and may show minimal manifestations (see Clinical Description, Mild HED).
  • If the proband represents a simplex case (i.e., a single occurrence in the family) and if the EDA pathogenic variant cannot be detected in the leukocyte DNA of the mother, the risk to sibs is presumed to be slightly greater than that of the general population (though still <1%) because of the theoretic possibility of maternal germline mosaicism.

Sibs of a female proband. The risk to sibs depends on the genetic status of the parents:

  • If the mother of the proband has an EDA pathogenic variant, the chance of transmitting it in each pregnancy is 50%. Males who inherit the pathogenic variant will be affected; females who inherit the pathogenic variant will be heterozygotes and may show minimal manifestations (see Mild HED).
  • If the father of the proband has an EDA pathogenic variant, he will transmit it to all of his daughters and none of his sons.

Offspring of a male proband. Affected males transmit the EDA pathogenic variant to:

  • All of their daughters, who will be heterozygotes and may show minimal manifestations (see Mild HED);
  • None of their sons.

Offspring of a female proband. Women with an EDA pathogenic variant have a 50% chance of transmitting the pathogenic variant to each child:

Other family members. The risk to other family members depends on the status of the proband's parents: if a parent is affected or has a pathogenic variant, family members are at risk.

Heterozygote (Carrier) Detection

Molecular genetic testing for carrier detection of at-risk female relatives is possible if the EDA pathogenic variant in the family is known.

Detection of heterozygotes on the basis of clinical findings is often imprecise. If sweat distribution is patchy or many teeth are absent, establishing carrier status is relatively easy. Otherwise, mild manifestations overlap with features in the general population. Hypodontia, for instance, is relatively common in the general population, and absence of one or two teeth in the mother of an affected male may be coincidental. Furthermore, there are no useful standards to judge hair density, and reports of sweat dysfunction, often judged by heat intolerance, are notoriously inaccurate.

Risk to Family Members ‒ Autosomal Recessive Hypohidrotic Ectodermal Dysplasia (ARHED)

Parents of a proband

  • The parents of an affected child are obligate heterozygotes (i.e., carriers of a pathogenic variant in EDAR, EDARADD, or WNT10A).
  • Heterozygotes (carriers) can be symptomatic and have mild features of the disorder, especially individuals heterozygous for a WNT10A pathogenic variant.

Sibs of a proband

  • At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
  • Heterozygotes (carriers) can be symptomatic and may have mild features of the disorder, especially individuals heterozygous for a WNT10A pathogenic variant.

Offspring of a proband. The offspring of an individual with ARHED are obligate heterozygotes (carriers) for a pathogenic variant in EDAR, EDARADD, or WNT10A.

Other family members. Each sib of the proband’s parents is at a 50% risk of being a carrier of an EDAR, EDARADD, or WNT10A pathogenic variant.

Carrier (Heterozygote) Detection

Carrier testing for at-risk relatives requires prior identification of the EDAR, EDARADD, or WNT10A pathogenic variants in the family.

Risk to Family Members – Autosomal Dominant Hypohidrotic Ectodermal Dysplasia (ADHED)

Parents of a proband

  • Some individuals diagnosed with ADHED have an affected parent.
  • A proband with ADHED may have the disorder as the result of a de novo EDAR, EDARADD, or WNT10A pathogenic variant. The proportion of cases caused by a de novo pathogenic variant is unknown.
  • Recommendations for the evaluation of parents of a proband with an apparent de novo pathogenic variant include physical examination and molecular genetic testing for the EDAR, EDARADD, or WNT10A pathogenic variant identified in the proband.
  • If the pathogenic variant found in the proband cannot be detected in leukocyte DNA of either parent, possible explanations include a de novo pathogenic variant in the proband or germline mosaicism in a parent. Though theoretically possible, no instances of germline mosaicism have been reported.
  • Note: Although individuals diagnosed with ADHED may have an affected parent, the family history may appear to be negative because of failure to recognize the disorder in family members, early death of the parent before the onset of symptoms, or late onset of the disease in the affected parent.

Sibs of a proband. The risk to sibs depends on the genetic status of the proband's parent:

  • If one of the proband's parents is affected, the risk to the sibs is 50%.
  • If the EDAR, EDARADD, or WNT10A pathogenic variant found in the proband cannot be detected in the leukocyte DNA of either parent, the risk to sibs is presumed to be slightly greater than that of the general population (though still <1%) because of the theoretic possibility of parental germline mosaicism.

Offspring of a proband. Each child of an individual with ADHED has a 50% chance of inheriting the EDAR, EDARADD, or WNT10A pathogenic variant.

Other family members. The risk to other family members depends on the status of the proband's parents: if a parent has the EDAR, EDARADD, or WNT10A pathogenic variant, his or her family members may be at risk.

Related Genetic Counseling Issues

See Management, Evaluation of Relatives at Risk for information on evaluating at-risk relatives for the purpose of early diagnosis and treatment.

Family planning

  • The optimal time for determination of genetic risk, clarification of carrier status, and discussion of the availability of prenatal testing is before pregnancy.
  • It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected, are carriers, or are at risk of being carriers.

DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, allelic variants, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals.

Prenatal Testing and Preimplantation Genetic Diagnosis

Once the EDA, EDAR, EDARADD, or WNT10A pathogenic variant(s) have been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic diagnosis for HED are possible.

Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing, particularly if the testing is being considered for the purpose of pregnancy termination rather than early diagnosis. While most centers would consider decisions regarding prenatal testing to be the choice of the parents, discussion of these issues is appropriate.

Resources

GeneReviews staff has selected the following disease-specific and/or umbrella support organizations and/or registries for the benefit of individuals with this disorder and their families. GeneReviews is not responsible for the information provided by other organizations. For information on selection criteria, click here.

  • Asociación de Afectados por Displasia Ectodérmica
    Consumer health-oriented organization for Spain.
    C Poet Andres Bolarín
    2-3º Dcha.
    Murcia 30011
    Spain
    Phone: 968 350 026
    Email: info@displasiaectodermica.org
  • Ectodermal Dysplasia Society
    108 Charlton Lane
    Cheltenham Gloucestershire GL53 9EA
    United Kingdom
    Phone: 01242 261332
    Email: diana@ectodermaldysplasia.org
  • Ectodermal Dysplasia Society: International Network of Organizations Supporting Those Affected by Ectodermal Dysplasias
  • Medline Plus
  • My46 Trait Profile
  • National Foundation for Ectodermal Dysplasias (NFED)
    410 East Main Street
    PO Box 114
    Mascoutah IL 62258-0114
    Phone: 618-566-2020
    Fax: 618-566-4718
    Email: info@nfed.org
  • National Library of Medicine Genetics Home Reference
  • Selbsthilfegruppe Ektodermale Dysplasie e.V.
    Consumer health-oriented organization for Germany, Austria, and Switzerland
    Landhausweg 3
    Aichtal D-72631
    Germany
    Phone: 0 71 27 96 96 91
    Fax: 0 71 27 96 96 92
    Email: Burk-Aichtal@t-online.de
  • Ectodermal Dysplasias International Registry
    National Foundation for Ectodermal Dysplasias
    410 East Main Street
    Mascoutah IL 62258
    Phone: 618-566-2020
    Fax: 618-566-4718
    Email: info@nfed.org

Molecular Genetics

Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED.

Table A.

Hypohidrotic Ectodermal Dysplasia: Genes and Databases

Data are compiled from the following standard references: gene from HGNC; chromosome locus from OMIM; protein from UniProt. For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click here.

Table B.

OMIM Entries for Hypohidrotic Ectodermal Dysplasia (View All in OMIM)

129490ECTODERMAL DYSPLASIA 10A, HYPOHIDROTIC/HAIR/NAIL TYPE, AUTOSOMAL DOMINANT; ECTD10A
224900ECTODERMAL DYSPLASIA 10B, HYPOHIDROTIC/HAIR/TOOTH TYPE, AUTOSOMAL RECESSIVE; ECTD10B
300451ECTODYSPLASIN A; EDA
305100ECTODERMAL DYSPLASIA 1, HYPOHIDROTIC, X-LINKED; XHED
604095ECTODYSPLASIN A RECEPTOR; EDAR
606268WINGLESS-TYPE MMTV INTEGRATION SITE FAMILY, MEMBER 10A; WNT10A
606603EDAR-ASSOCIATED DEATH DOMAIN; EDARADD
614941ECTODERMAL DYSPLASIA 11B, HYPOHIDROTIC/HAIR/TOOTH TYPE, AUTOSOMAL RECESSIVE; ECTD11B

Molecular Genetic Pathogenesis

The molecular pathogenesis of hypohidrotic ectodermal dysplasia (HED) is not fully understood. EDA, the gene responsible for X-linked HED, produces ectodysplasin-A, a protein that is important for normal development of ectodermal appendages including hair, teeth, and sweat glands. Evidence is accumulating that ectodysplasin-A is important in several pathways that involve ectodermal-mesodermal interactions during embryogenesis. Defects in the molecular structure of ectodysplasin-A may inhibit the action of enzymes necessary for normal development of the ectoderm and/or its interaction with the underlying mesoderm.

EDA

Gene structure. EDA is an X-linked gene that comprises 12 exons, eight of which encode the transmembrane protein ectodysplasin-A [Bayés et al 1998, Ferguson et al 1998, Monreal et al 1998] (Reference sequence NM_001399.4). For a detailed summary of gene and protein information, see Table A, Gene.

Pathogenic variants. Numerous pathogenic variants including nucleotide substitutions (missense, nonsense, and splicing), small deletions and insertions, and gross deletions have been identified in EDA [Visinoni et al 2003, Hsu et al 2004].

Normal gene product. Ectodysplasin-A has 391 amino acid residues with a short collagenous domain (Gly-X-Y) that is homologous to the protein encoded by the mouse gene Eda. Ezer et al [1999] demonstrated that ectodysplasin-A is a trimeric type II protein that colocalizes with cytoskeletal structures at the lateral and apical surfaces of cells, suggesting that it is a novel member of the tumor necrosis factor (TNF)-related ligand family that plays a role in early epithelial-mesenchyme interactions. Several isoforms of ectodysplasin are expressed in keratinocytes, hair follicles, and sweat glands (Reference sequence NP_001390.1).

Abnormal gene product. Pathogenic variants in EDA lead to ectodysplasin A molecules that are unable to regulate epithelial-mesenchyme interactions, resulting in abnormal ectodermal appendages. Several pathogenic variants in EDA produce ectodysplasin A molecules that resist cleavage by furin and are consequently unable to be converted to their active forms and mediate the cell-to-cell signaling that regulates morphogenesis of ectodermal appendages [Chen et al 2001].

EDAR

Gene structure. Human EDAR has 12 exons (NM_022336.3). EDAR is orthologous to the mouse gene Edar. For a detailed summary of gene and protein information, see Table A, Gene.

Pathogenic variants. Several pathogenic variants have been identified in EDAR, including deletions, transitions, and a gross deletion [Monreal et al 1999, Shimomura et al 2004, Chassaing et al 2006, Mégarbané et al 2008, van der Hout et al 2008].

Table 2.

EDAR Pathogenic Variants Discussed in This GeneReview

DNA Nucleotide ChangePredicted Protein ChangeReference Sequences
c.803+1G>ANM_022336​.3
NP_071731​.1
c.338G>Ap.Cys113Tyr

Note on variant classification: Variants listed in the table have been provided by the authors. GeneReviews staff have not independently verified the classification of variants.

Note on nomenclature: GeneReviews follows the standard naming conventions of the Human Genome Variation Society (varnomen​.hgvs.org). See Quick Reference for an explanation of nomenclature.

Normal gene product. EDAR encodes a 448-amino acid protein that contains a single transmembrane domain with type 1 membrane topology. The protein probably functions as a multimeric receptor and is related to the TNFR family. It forms a ligand-receptor pair with ectodysplasin (NP_071731.1).

Abnormal gene product. The defective proteins encoded by pathogenic variants in EDAR are unable to bind with ectodysplasin. Those responsible for autosomal recessive HED exhibit loss of function, while those responsible for autosomal dominant HED exhibit a dominant negative effect [Valcuende-Cavero et al 2008]. At least two of the dominant negative pathogenic variants are not associated with the HED phenotype.

EDARADD

Gene structure. Human EDARADD has two isoforms, each with six exons encoding 205 and 215 amino acid proteins (NM_080738.3 and NM_145861.2, respectively). EDARADD is homologous to the mouse gene Edaradd. For a detailed summary of gene and protein information, see Table A, Gene.

Pathogenic variants. A p.Glu142Lys missense variant has been identified in an inbred family with autosomal recessive HED [Headon et al 2001]. Another family with autosomal dominant HED has been found to have a heterozygous p.Leu112Arg pathogenic variant in EDARADD, indicating that both recessive and dominant forms of HED can be caused by EDARADD pathogenic variants [Bal et al 2007]. A homozygous 6-bp in-frame deletion (p.Thr135_Val136del) has also been reported in an individual with HED [Chassaing et al 2010].

Table 3.

EDARADD Pathogenic Variants Discussed in This GeneReview

DNA Nucleotide ChangePredicted Protein ChangeReference Sequences
c.335T>Gp.Leu112ArgNM_080738​.3
NP_542776​.1
c.372_377del
(402_407del) 1
p.Thr125_Val126del
(Thr135-Val136del) 1
c.424G>Ap.Glu142Lys

Note on variant classification: Variants listed in the table have been provided by the authors. GeneReviews staff have not independently verified the classification of variants.

Note on nomenclature: GeneReviews follows the standard naming conventions of the Human Genome Variation Society (varnomen​.hgvs.org). See Quick Reference for an explanation of nomenclature.

1.

Numbering according to the longer transcript variant and protein isoform (NM_145861​.2; NP_665860​.2).

Normal gene product. The protein encoded by EDARADD is similar to the death domain, MyD88, a cytoplasmic transducer of Toll/interleukin receptor signaling [Headon et al 2001]. It also contains a Traf-binding consensus sequence. It is coexpressed with tumor necrosis factor receptor superfamily member EDAR in epithelial cells during the formation of hair follicles and teeth. It interacts with the death domain of EDAR and links the receptor to signaling pathways downstream.

Abnormal gene product. EDARADD pathogenic variants alter the charge of an amino acid in the protein, usually rendering it unable to interact with EDAR. In one family with autosomal dominant HED, a novel missense variant did not interfere with interaction between EDAR and EDARADD proteins but still lead to impaired activation of NF-kappa B signaling [Wohlfart et al 2016].

WNT10A

Gene structure. WNT10A contains four exons and maps to chromosome 2q35 near WNT6.

Pathogenic variants. A c.321C>A (p.Cys107Ter) nonsense variant is one of the most common WNT10A pathogenic variants. A c.682T>A (p.Phe228Ile) missense variant is also very common. Multiple other missense and nonsense variants have been described [Bohring et al 2009, Cluzeau et al 2011, Mues et al 2014, Bergendal et al 2016].

Table 4.

WNT10A Pathogenic Variants Discussed in This GeneReview

DNA Nucleotide ChangePredicted Protein ChangeReference Sequences
c.321C>Ap.Cys107TerNM_025216​.2
NP_079492​.2
c.682T>Ap.Phe228Ile

Note on variant classification: Variants listed in the table have been provided by the authors. GeneReviews staff have not independently verified the classification of variants.

Note on nomenclature: GeneReviews follows the standard naming conventions of the Human Genome Variation Society (varnomen​.hgvs.org). See Quick Reference for an explanation of nomenclature.

Normal gene product. WNT10A encodes a 417-amino acid peptide containing two N-linked glycosylation sites and residues conserved among WNTs. The protein contains two domains, a signal peptide and the Wnt domain and encodes a secreted signaling molecule that is involved in several developmental processes, such as regulation of cell fate and patterning during embryogenesis. WNT10A and WNT10B are highly expressed in embryonic skin as well as the placodes involved in follicle morphogenesis. WNT10A is also very important for normal dentinogenesis and tooth morphogenesis.

Abnormal gene product. The WNT signal transduction pathway is essential for the development of ectodermally derived tissues. Therefore, WNT10A pathogenic variants are associated with lack of normal development of the dentition most frequently, but also affect other ectodermal structures including sweat glands, hair and nails.

References

Literature Cited

  • Bal E, Baala L, Cluzeau C, El Kerch F, Ouldim K, Hadj-Rabia S, Bodemer C, Munnich A, Courtois G, Sefiani A, Smahi A. Autosomal dominant anhidrotic ectodermal dysplasias at the EDARADD locus. Hum Mutat. 2007;28:703–9. [PubMed: 17354266]
  • Bayés M, Hartung AJ, Ezer S, Pispa J, Thesleff I, Srivastava AK, Kere J. The anhidrotic ectodermal dysplasia gene (EDA) undergoes alternative splicing and encodes ectodysplasin-A with deletion mutations in collagenous repeats. Hum Mol Genet. 1998;7:1661–9. [PubMed: 9736768]
  • Bergendal B, Klar J, Stecksén-Blicks C, Norderyd J, Dahl N. Isolated oligodontia associated with mutations in EDARADD, AXIN2, MSX1, and PAX9 genes. Am J Med Genet A. 2011;155A:1616–22. [PubMed: 21626677]
  • Bergendal B, Norderyd J, Zhou X, Klar J, Dahl N. Abnormal primary and permanent dentitions with ectodermal symptoms predict WNT10A deficiency. BMC Medical Genetics. 2016;17:88. [PMC free article: PMC5122154] [PubMed: 27881089]
  • Blüschke G, Nüsken KD, Schneider H. Prevalence and prevention of severe complications of hypohidrotic ectodermal dysplasia in infancy. Early Hum Dev. 2010;86:397–9. [PubMed: 20682465]
  • Bohring A, Stamm T, Spaich C, Haase C, Spree K, Hehr U, Hoffmann M, Ledig S, Sel S, Wieacker P, Röpke A. 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;85:97–105. [PMC free article: PMC2706962] [PubMed: 19559398]
  • Cambiaghi S, Restano L, Paakkonen K, Caputo R, Kere J. Clinical findings in mosaic carriers of hypohidrotic ectodermal dysplasia. Arch Dermatol. 2000;136:217–24. [PubMed: 10677098]
  • Carrol ED, Gennery AR, Flood TJ, Spickett GP, Abinun M. Anhidrotic ectodermal dysplasia and immunodeficiency: the role of NEMO. Arch Dis Child. 2003;88:340–1. [PMC free article: PMC1719512] [PubMed: 12651765]
  • Castori M, Ruggieri S, Giannetti L, Annessi G, Zambruno G. Schöpf-Schulz-Passarge syndrome: further delineation of the phenotype and genetic considerations. Acta Derm Venereol. 2008;88:607–12. [PubMed: 19002348]
  • Castori M, Castiglia D, Brancati F, Foglio M, Heath S, Floriddia G, Madonna S, Fischer J, Zambruno G. Two families confirm Schöpf-Schulz-Passarge syndrome as a discrete entity within the WNT10A phenotypic spectrum. Clin Genet. 2011;79:92–5. [PubMed: 21143469]
  • Chassaing N, Cluzeau C, Bal E, Guigue P, Vincent MC, Viot G, Ginisty D, Munnich A, Smahi A, Calvas P. Mutations in EDARADD account for a small proportion of hypohidrotic ectodermal dysplasia cases. Br J Dermatol. 2010;162:1044–8. [PubMed: 20222921]
  • Chassaing N, Bourthoumieu S, Cossee M, Calvas P, Vincent MC. Mutations in EDAR account for one-quarter of non-ED1-related hypohidrotic ectodermal dysplasia. Hum Mutat. 2006;27:255–9. [PubMed: 16435307]
  • Chen Y, Molloy SS, Thomas L, Gambee J, Bachinger HP, Ferguson B, Zonana J, Thomas G, Morris NP. Mutations within a furin consensus sequence block proteolytic release of ectodysplasin-A and cause X-linked hypohidrotic ectodermal dysplasia. Proc Natl Acad Sci U S A. 2001;98:7218–23. [PMC free article: PMC34649] [PubMed: 11416205]
  • Cluzeau C, Hadj-Rabia S, Jambou M, Mansour S, Guigue P, Masmoudi S, Bal E, Chassaing N, Vincent MC, Viot G, Clauss F, Manière MC, Toupenay S, Le Merrer M, Lyonnet S, Cormier-Daire V, Amiel J, Faivre L, de Prost Y, Munnich A, Bonnefont JP, Bodemer C, Smahi A. Only four genes (EDA1, EDAR, EDARADD, and WNT10A) account for 90% of hypohidrotic/anhidrotic ectodermal dysplasia cases. Hum Mutat. 2011;32:70–2. [PubMed: 20979233]
  • Dietz J, Kaercher T, Schneider AT, Zimmermann T, Huttner K, Johnson R, Schneider H. Early respiratory and ocular involvement in X-linked hypohidrotic ectodermal dysplasia. Eur J Pediatr. 2013;172:1023–31. [PubMed: 23553579]
  • Döffinger R, Smahi A, Bessia C, Geissmann F, Feinberg J, Durandy A, Bodemer C, Kenwrick S, Dupuis-Girod S, Blanche S, Wood P, Rabia SH, Headon DJ, Overbeek PA, Le Deist F, Holland SM, Belani K, Kumararatne DS, Fischer A, Shapiro R, Conley ME, Reimund E, Kalhoff H, Abinun M, Munnich A, Israël A, Courtois G, Casanova JL. X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-kappaB signaling. Nat Genet. 2001;27:277–85. [PubMed: 11242109]
  • Ezer S, Bayés M, Elomaa O, Schlessinger D, Kere J. Ectodysplasin is a collagenous trimeric type II membrane protein with a tumor necrosis factor-like domain and co-localizes with cytoskeletal structures at lateral and apical surfaces of cells. Hum Mol Genet. 1999;8:2079–86. [PubMed: 10484778]
  • Ferguson BM, Thomas NS, Munoz F, Morgan D, Clarke A, Zonana J. Scarcity of mutations detected in families with X linked hypohidrotic ectodermal dysplasia: diagnostic implications. J Med Genet. 1998;35:112–5. [PMC free article: PMC1051213] [PubMed: 9507389]
  • 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;164A:2437–42. [PubMed: 24664614]
  • Haghighi A, Nikuei P, Haghighi-Kakhki H, Saleh-Gohari N, Baghestani S, Krawitz PM, Hecht J, Mundlos S. Whole-exome sequencing identifies a novel missense mutation in EDAR causing autosomal recessive hypohidrotic ectodermal dysplasia with bilateral amastia and palmoplantar hyperkeratosis. Br J Dermatol. 2013;168:1353–6. [PubMed: 23210707]
  • Headon DJ, Emmal SA, Ferguson BM, Tucker AS, Justice MJ, Sharpe PT, Zonana J, Overbeek PA. Gene defect in ectodermal dysplasia implicates a death domain adapter in development. Nature. 2001;414:913–6. [PubMed: 11780064]
  • Ho L, Williams MS, Spritz RA. A gene for autosomal dominant hypohidrotic ectodermal dysplasia (EDA3) maps to chromosome 2q11-q13. Am J Hum Genet. 1998;62:1102–6. [PMC free article: PMC1377096] [PubMed: 9545409]
  • Hsu MM, Chao SC, Lu AC. Gene Symbol: ED1. Disease: Ectodermal dysplasia, anhidrotic. Hum Genet. 2004;114:609. [PubMed: 15176392]
  • Huttner K. Future developments in XLHED treatment approaches. Am J Med Genet. 2014;164A:2433–6. [PubMed: 24678015]
  • Jones KB, Goodwin AF, Landan M, Seidel K, Tran DK, Hogue J, Chavez M, Fete M, Yu W, Hussein T, Johnson R, Huttner K, Jheon AH, Klein OD. 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;161A:1585–93. [PMC free article: PMC4414120] [PubMed: 23687000]
  • Kramer FJ, Baethge C, Tschernitschek H. Implants in children with ectodermal dysplasia: a case report and literature review. Clin Oral Implants Res. 2007;18:140–6. [PubMed: 17224035]
  • Krøigård AB, Clemmensen O, Gjørup H, Hertz JM, Bygum A. Odonto-onycho-dermal dysplasia in a patient homozygous for a WNT10A nonsense mutation and mild manifestations of ectodermal dysplasia in carriers of the mutation. BMC Dermatol. 2016;16:3. [PMC free article: PMC4785680] [PubMed: 26964878]
  • 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;68:e139–40. [PubMed: 23522427]
  • Lexner MO, Bardow A, Hertz JM, Nielsen LA, Kreiborg S. Anomalies of tooth formation in hypohidrotic ectodermal dysplasia. Int J Paediatr Dent. 2007;17:10–8. [PubMed: 17181574]
  • Lexner MO, Bardow A, Juncker I, Jensen LG, Almer L, Kreiborg S, Hertz JM. X-linked hypohidrotic ectodermal dysplasia. Genetic and dental findings in 67 Danish patients from 19 families. Clin Genet. 2008;74:252–9. [PubMed: 18510547]
  • Lopez-Granados E, Keenan JE, Kinney MC, Leo H, Jain N, Ma CA, Quinones R, Gelfand EW, Jain A. A novel mutation in NFKBIA/IKBA results in a degradation-resistant N-truncated protein and is associated with ectodermal dysplasia with immunodeficiency. Hum Mutat. 2008;29:861–8. [PMC free article: PMC3179847] [PubMed: 18412279]
  • Mehta U, Brunworth J, Lewis RA, Sindwani R. Rhinologic manifestations of ectodermal dysplasia. Am J Rhinol. 2007;21:55–8. [PubMed: 17283562]
  • Mégarbané H, Cluzeau C, Bodemer C, Fraïtag S, Chababi-Atallah M, Mégarbané A, Smahi A. Unusual presentation of a severe autosomal recessive anhydrotic ectodermal dysplasia with a novel mutation in the EDAR gene. Am J Med Genet A. 2008;146A:2657–62. [PubMed: 18816645]
  • 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;22:366–9. [PubMed: 10431241]
  • 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. Am J Hum Genet. 1998;63:380–9. [PMC free article: PMC1377324] [PubMed: 9683615]
  • Mues G, Bonds J, Xiang L, Vieira AR, Seymen F, Klein O, D’Souza RN. The WNT10A gene in ectodermal dysplasias and selective tooth agenesis. Am J Med Genet. 2014;164A:2455–60. [PMC free article: PMC4167166] [PubMed: 24700731]
  • Nagy N, Wedgeworth E, Hamada T, White JM, Hashimoto T, McGrath JA. Schöpf-Schulz-Passarge syndrome resulting from a homozygous nonsense mutation in WNT10A. J Dermatol Sci. 2010;58:220–2. [PubMed: 20418069]
  • Plaisancié J, Bailleul-Forestier I, Gaston V, Vaysse F, Lacombe D, Holder-Espinasse M, Abramowicz M, Coubes C, Plessis G, Faivre L, Demeer B, Vincent-Delorme C, Dollfus H, Sigaudy S, Guillén-Navarro E, Verloes A, Jonveaux P, Martin-Coignard D, Colin E, Bieth E, Calvas P, Chassaing N. Mutations in WNT10A are frequently involved in oligodontia associated with minor signs of ectodermal dysplasia. Am J Med Genet A. 2013;161A:671–8. [PubMed: 23401279]
  • Rasool M, Schuster J, Aslam M, Tariq M, Ahmad I, Ali A, Entesarian M, Dahl N, Baig SM. A novel missense mutation in the EDA gene associated with X-linked recessive isolated hypodontia. J Hum Genet. 2008;53:894–8. [PubMed: 18688569]
  • Rouse C, Siegfried E, Breer W, Nahass G. Hair and sweat glands in families with hypohidrotic ectodermal dysplasia: further characterization. Arch Dermatol. 2004;140:850–5. [PubMed: 15262696]
  • Schneider H, Hammersen J, Preisler-Adams S, Huttner K, Rascher W, Bohring A. Sweating ability and genotype in individuals with X-linked hypohidrotic ectodermal dysplasia. J Med Genet. 2011;48:426–32. [PubMed: 21357618]
  • Shimomura Y, Sato N, Miyashita A, Hashimoto T, Ito M, Kuwano R. A rare case of hypohidrotic ectodermal dysplasia caused by compound heterozygous mutations in the EDAR gene. J Invest Dermatol. 2004;123:649–55. [PubMed: 15373768]
  • Stanford CM, Guckes A, Fete M, Srun S, Richter MK. Perceptions of outcomes of implant therapy in patients with ectodermal dysplasia syndromes. Int J Prosthodont. 2008;21:195–200. [PubMed: 18548955]
  • Valcuende-Cavero F, Martinez F, Pérez-Pastor G, Oltra S, Ferrer I, Tomás-Cabedo G, Moreno-Presmanes M. Autosomal-dominant hypohidrotic ectodermal dysplasia caused by a novel mutation. J Eur Acad Dermatol Venereol. 2008;22:1508–10. [PubMed: 18384562]
  • van der Hout AH, Oudesluijs GG, Venema A, Verheij JB, Mol BG, Rump P, Brunner HG, Vos YJ, van Essen AJ. Mutation screening of the Ectodysplasin-A receptor gene EDAR in hypohidrotic ectodermal dysplasia. Eur J Hum Genet. 2008;16:673–9. [PubMed: 18231121]
  • Visinoni AF, de Souza RL, Freire-Maia N, Gollop TR, Chautard-Freire-Maia EA. X-linked hypohidrotic ectodermal dysplasia mutations in Brazilian families. Am J Med Genet A. 2003;122A:51–5. [PubMed: 12949972]
  • Wohlfart S, Söder S, Smahi A, Schneider H. A novel missense mutation in the gene EDARADD associated with an unusual phenotype of hypohidrotic ectodermal dysplasia. Am J Med Genet. 2016;170A:249–53. [PubMed: 26440664]
  • Zhang J, Han D, Song S, Wang Y, Zhao H, Pan S, Bai B, Feng H. Correlation between the phenotypes and genotypes of X-linked hypohidrotic ectodermal dysplasia and non-syndromic hypodontia caused by ectodysplasin-A mutations. Eur J Med Genet. 2011;54:e377–82. [PubMed: 21457804]
  • Zonana J, Elder ME, Schneider LC, Orlow SJ, Moss C, Golabi M, Shapira SK, Farndon PA, Wara DW, Emmal SA, Ferguson BM. 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;67:1555–62. [PMC free article: PMC1287930] [PubMed: 11047757]

Chapter Notes

Acknowledgments

Ronald J Jorgenson, DDS, PhD

National Foundation for Ectodermal Dysplasias

Author History

Mary Fete, MSN, RN, CCM (2017-present)
Dorothy K Grange, MD (2006-present)
Ronald J Jorgenson, DDS, PhD; former President, Applied Genetics, Austin, Texas (2002-2006)
Mary K Richter; National Foundation for Ectodermal Dysplasias (2006-2017)
J Timothy Wright, DDS, MS (2006-present)

Revision History

  • 1 June 2017 (sw) Comprehensive update posted live
  • 15 May 2014 (me) Comprehensive update posted live
  • 13 June 2013 (aa) Revision: EDAR deletion reported
  • 29 December 2011 (me) Comprehensive update posted live
  • 23 July 2009 (me) Comprehensive update posted live
  • 16 November 2006 (me) Comprehensive update posted live
  • 28 April 2003 (me) Review posted live
  • 23 October 2002 (rj) Original submission
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