Ectodermal Dysplasia Clinical Presentation

Updated: Feb 24, 2016
  • Author: Kara N Shah, MD, PhD; Chief Editor: Dirk M Elston, MD  more...
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Presentation

History

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:

  • Hyperthermia with fever and seizures

  • Xerophthalmia (decreased tears) and conjunctivitis [15]

  • Deficient hearing or vision

  • Xerostomia (decreased saliva) [16] and frequent dental caries

  • Developmental delay or mental retardation

  • Dysphagia

  • Growth failure [17]

  • Signs of airway constriction and inflammation [18]

  • Frequent pharyngitis, otitis, and rhinitis; nasal obstruction; hearing loss; and hoarseness [19, 20, 21]

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Physical

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

  • Dry, hypopigmented skin is a feature. A chronic eczematous dermatitis may be present.

  • Sweating may be absent or reduced.

  • Sparse, fair, brittle hair with alopecia is a feature, as are absent or diminished body hair and sparse or absent eyebrows and eyelashes.

  • Nail dystrophy is a feature.

  • Dental features may include hypodontia or anodontia; malformed, rudimentary, or pegged teeth; and/or enamel defects and frequent dental caries. [22]

  • Diminished lacrimation and salivation are reported.

  • Dysmorphic facies is a feature.

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. [23]

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.

Wrinkled, hyperpigmented skin around the eyes and 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. [24, 25, 26]

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. [27] 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. [28] 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. [29] 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. [30]

Rapp-Hodgkin ectodermal dysplasia

Rapp-Hodgkin ectodermal dysplasia is an autosomal dominant syndrome. [31] 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.

Abnormal hair shaft showing pili torti and a longi 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 Hands of father and son with Rapp-Hodgkin syndrome. Nails have the same characteristics; they are brittle, thin, and dystrophic.
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Causes

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. [32, 33] 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. [34]

Autosomal dominant and autosomal recessive hypohidrotic ectodermal dysplasia are caused by mutations in the DL gene, which encodes the EDA (ectodysplasin) receptor. [35] 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. [36]

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. [37]

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. [38, 39, 40]

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. [41, 42] 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:

  • Keratitis, ichthyosis, deafness (KID) syndrome is caused by mutations in the GJB2 gene, which encodes connexin 26. [43]

  • Margarita Island ectodermal dysplasia is caused by mutations in the PVRL1 gene, which encodes nectin-1. [44]

  • Ectodermal dysplasia with skin fragility is caused by mutations in the PKP1 gene, which encodes plakophilin 1. [45]

  • Goltz syndrome (focal dermal hypoplasia) is caused by mutations in the PORCN gene. [46]

  • Naegeli-Franceschetti-Jadassohn syndrome and dermatopathia pigmentosa reticularis are caused by mutations in the KRT14 gene, which encodes keratin 14. [47]

  • Pachyonychia congenita type I is caused by mutations in either KRT6A (keratin 6a) or KRT16 (keratin 16), while pachyonychia congenita type II is caused by mutations in either KRT6B (keratin 6b) or KRT17 (keratin 17). [48, 49, 50]

  • Ellis-van Creveld syndrome is cause by mutations in EVC or EVC2. [51, 52, 53]

  • Pure hair and nail ectodermal dysplasia has been demonstrated to be caused by mutations in 2 different genes to date: HOXC13 and KRT85. [54, 55, 56]

  • Incontinentia pigmenti is caused by mutations in NEMO, or NF-kB essential modulator. [57]

  • Odonto-onycho-dermal dysplasia (OODD), Schopf-Schultz-Passarge syndrome, selective tooth agenesis, and related forms of ectodermal dysplasia are caused by mutations in WNT10A. [58, 59, 60, 61]

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