Ectodermal dysplasia in identical twins.

Hereditary hypohidrotic ectodermal dysplasia (HED) is typically inherited as an X-linked recessive trait, characterized by deformity of at least two or more of the ectodermal structures - hair, teeth, nails and sweat glands. Two cases of hereditary HED involving identical male twins, is being documented for the rarity of its occurrence with special attention given to genetics, pathophysiology, clinical, intraoral manifestations and to the methods to improve the masticatory function, the facial esthetics and psychology of patients affected by this disease.

Ectodermal dysplasia (EDA) is a large group of inherited disorders characterized by a primary defect in hair, teeth, nails or sweat gland function, in addition to other abnormalities in a tissue of ectodermal origin, e.g., ears, eyes, lips, mucous membranes of the mouth or nose, central nervous system.[1] The ectoderm is the outermost layer of cells in embryonic development and contributes to the formation of many parts of the body including all those described above. EDA occurs when the ectoderm of certain areas fails to develop normally. All EDAs are present from birth and are non-progressive.[2] Defects in tissues derived from other embryologic layers are not uncommon.[3]

Case Report

A 23-year-old boy presented with a complaint of missing teeth with difficulty in speaking and eating to Farooqia Dental College and Hospital. He was moderately built, poorly nourished and had the typical face of EDA with features like: Frontal bossing, prominent supraorbital ridges, perioral pigmentation, dry skin, depressed nasal bridge, protuberant lips, low-set ears, recession of hair line all along with fine, sparse scanty scalp hair, scanty eyebrow and eye lashes. The left eye was slightly smaller than the right eye and the nails were not very brittle [Figures 1-4]. Informed consent was procured from patients before any findings were reported. He was accompanied by his mother who gave a history of a total of six children born of a non-consanguineous marriage, with the boy and his younger male identical twin also suffering from the same condition since birth [Figure 1]. No other members of the family suffered from this trait. The mother also gave a history of the twins, presenting with partial anodontia in the upper jaw, complete anodontia of the lower jaw, progressive hyper pigmentation around eyes and mouth, complete absence of sweating since birth, repeated episodes of unexplained hyperpyrexia and thirst, which necessitated consistent drinking of cold water. They were of normal intelligence.

Figure 1

23 yrs old male identical twins

Figure 4

Nail defects were not evident

Profile view

Sparse, thin, lusterless scalp hair

Medical history revealed that the boy complained of frequent headache, dry eyes and poor vision in the left eye. Other systems were within normal limits. Intraoral examination revealed partial anodontia of the maxillary arch with the presence of four teeth suggestive of maxillary central incisors and canines on either side of the midline. The mandibular arch was completely edentulous with poorly developed alveolus. Moderate dryness of the mouth, with inflamed mucosa was evident [Figure 5]. A panoramic radiograph showed the presence of four cone-shaped crowns with roots in the maxilla consistent with central incisors and canines on either side of the midline. The mandibular alveolar ridge was narrow with complete anodontia and with evidence of right impacted canine like tooth [Figure 6].

Figure 5

Intra-oral photograph

Figure 6

Panoramic photograph

The younger twin brother also presented with almost the same identical physical and medical findings. He demonstrated good vision with no marked asymmetry of the eyes and a slight increase in scalp hair. Intraoral examination was identical. Examination of the panoramic radiographs of the younger twin showed the presence of four cone-shaped crowns with roots in maxilla consistent with central incisors and canines on either side of the midline. The mandibular teeth were missing with a narrow alveolar ridge. Cephalogram revealed normal growth pattern in both the twins [Figure 7]. Examination of impression and working model [Figure 8] confirmed it. Since hypohidrosis, hypotrichosis and hypodontia were very evident on physical examination, the twins were diagnosed with hereditary hypohidrotic ectodermal dysplasia (HED) with partial anodontia. Treatment plan consisted of fixed partial dentures (FPD) for the conical shaped maxillary anterior teeth followed by construction of removable dentures.

Figure 7

Cephalogram

Figure 8

Secondary impression and working model of maxilla and mandible

Discussion

Thurnam, first reported EDA and the term EDA was coined in 1929 by Weech. EDAs is congenital, diffuse and non-progressive. To date, more than 192 distinct disorders have been described with the most common being X-linked recessive HED (Christ-Siemens-Touraine syndrome) and hidrotic EDA (Clouston syndrome). Current classification of EDAs is based on clinical features. Pure EDAs are manifested by defects in ectodermal structures alone while EDA 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 EDAs in 1982, with additional updates in 1994 and 2001. Their original classification system stratified the EDAs 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 EDAs were classified into either Group A disorders, which were manifested by defects in at least two of the four 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 (i.e., ears, lips, dermatoglyphics). Eleven Groups A subgroups were defined, each with a distinct combination of two or more ectodermal defects (e.g., 2-4, 1-2-3, 1-2-3-4 from above). The Group B disorders were indicated as 1-5, 2-5, 3-5, or 4-5 (from above). With the recent identification of the causative genetic defect for a number of the EDAs, newer classification systems have been devised. In 2003, Lamartine reclassified the EDAs into the following functional groups based on the underlying pathophysiologic defect: (1) Cell-to-cell communication and signaling, (2) adhesion, (3) development and (4) other. Similarly, in 2001, Priolo and Laganà reclassified the EDAs into two main functional groups: (1) Defects in developmental regulation/epithelial-mesenchymal interaction and (2) defects in cytoskeleton maintenance and cell stability. Several EDA syndromes may manifest in association with midfacial defects, mainly cleft lip, cleft palate or both. The three most commonly recognized entities are (1) EDA, ectrodactyly, and clefting syndrome (2) Hay-Wells syndrome or ankyloblepharon, EDA, and cleft lip/palate syndrome and (3) Rapp-Hodgkin syndrome, all of which are caused by mutations in the TP63 gene.

The prevelance of EDA is 7 estimated at seven cases/10,000 births,[3] the carriers-incidence is probably around 17.3 in 100,000 women.[4] 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.[35] A family history of similar clinical features is helpful.[6]

The typical facies, which is often not recognized until infancy, is characterized by frontal bossing, sunken cheeks, saddle nose, thick, everted lips, wrinkled, dry, hypopigmented skin with hyperpigmentation periorbitally and large, low-set ears. Onychodystrophy may occur but is not common and may result in brittle, thin, ridged, or grossly deformed nails. There may be developmental delay and short stature due to growth retardation, but intelligence is normal.[5] There is absent or diminished body hair, sparse or absent eyebrows and eyelashes due to a reduction in the number of hair follicles in conjunction with structural hair shaft abnormalities due to aberrations in the hair bulb formation (include longitudinal grooving, hair shaft torsion and cuticle ruffling). Hair bulbs may be distorted, bifid, or small resulting in sparse, fair, brittle 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. Eccrine sweat glands may be absent, sparse or rudimentary, which may present in early infancy as recurrent episodes of hyperpyrexia, which may also lead to seizures and neurological problems where in the mortality rate may approach 30%. The development of a chronic eczematous dermatitis is common. Other secretory gland defects include hypoplasia of the salivary and lacrimal glands resulting in xeostomia, Xerophthalmia, photophobia, conjunctivitis and defective vision. In some patients, Pharyngitis, rhinitis, cheilitis, and dysphagia may result from reduced numbers of functional mucous glands in the respiratory and gastrointestinal tracts. Dental defects include abnormal morphogenesis, (peg or conical shaped), hypodontia, delayed eruption or complete anodontia.[3] More often, most of the deciduous teeth form, but there are few or no permanent teeth. Patients with severe dental abnormalities may develop feeding difficulties, which may result in malnutrition and failure to thrive.[6] The cephalometric measurements, reveals the general facial growth proportion, and pattern of jaw growth appear to be normal in these children despite the absence of tooth development.[1] The alveolar ridges can remain severely hypotrophic due to oligo or anodontia in the primary and/or permanent dentition[7] resulting in protuberant lips due to the reduction in the height of the alveolar process.[3]

Other signs and symptoms include, deficient hearing and otitis.[5] The X-linked recessive HED has full expression only in males.[3] While female are carriers, show little or no signs of the condition.[3]

The genetic defects responsible for approximately 30 of the EDAs have been identified. X-linked recessive HED (EDA or Christ-Siemens-Touraine syndrome) is caused by mutations in EDA, which encodes the ectodysplasin protein, a soluble ligand that activates the nuclear factor-kappa B (NF-kappa B) and JNK/c-fos/c-jun signaling pathways.[3] The corresponding molecular mechanisms involve altered interactions between the EDA-NF-kappa B pathway and signaling molecules essential in skeletogenic neural crest cell differentiation, migration, and osteoclastic differentiation[7] autosomal dominant and autosomal recessive HED are caused by mutations in the DL gene, which encodes the EDA (ectodysplasin) receptor. Mutations in the ectodermal dysplasia receptor associated death domain (EDARADD) genes encoding the ectodermal dysplasia receptor (EDAR) and (less frequently) the adaptor protein that associates with the EDAR death domain result in autosomal dominant and autosomal recessive forms of HED.[8]

Genetic mapping showed linkage of family with autosomal recessive form of HED to EDAR gene on chromosome 2q11-q13 and family with X-linked recessive isolated hypodontia to EDA gene on chromosome Xq12-q13.1. Recurrence of mutations in EDAR and EDA genes in unrelated families is evocative of the dispersion of ancestral chromosome in a different locality groups through common ancestors.[9] The prognosis for most patients with ectodermal dysplasia is very good. If hypohidrosis is recognized in the neonatal period and managed appropriately, no evidence indicates that the life span of a person with Hypohidrotic ectodermal dysplasia (HED) is shorter than average.[5] However, the lack of sweat glands may lead to hyperthermia, followed by brain damage or death in early infancy if unrecognized. Thus an early diagnosis is important and families with EDA should therefore be offered genetic counseling.[4]

Crowns, FPD and direct composite restorations are often used to restore malformed teeth in combination with removable partial dentures and implant-supported prostheses in the Prosthodontic and psychological management of these patients. Periodic recalls are often necessary in young adults as a result of continuing growth and development that mandates adjustments in the prostheses. Dentures create conditions for maintenance of a normal, satisfactory daily diet, at an early age. Dentures help positioning of the chin in place, and prevents the anterorotation of the mandible, upward and forward displacement of the chin, a reduction in the height of the lower-third of the face; a tendency to C1 III malocclusion.[10]