Ectodermal Dysplasia: Variable Expressions

Dear Editor, Ectodermal dysplasia (ED) encompasses a diverse array of hereditary disorders, affecting approximately 1 in 10,000 to 1 in 100,000 live births.[1] They have many subtypes but the most common variant is hypohidrotic ED, also known as Christ-Siemens-Touraine syndrome, or anhidrotic dysplasia.[1] The most common inheritance pattern is X-linked recessive (>90%)[2] but autosomal dominant and recessive forms are also present. The genetic abnormality in X-linked ED is ectodysplasin (EDA1) gene, located on chromosome Xq12-q13.1.[3] We report a rare cluster of four patients with ED. This cluster presentation is noteworthy, as ED is typically reported as isolated cases making this series a unique and intriguing observation. Case #1 and 2 Two brothers, aged 22 and 24 years old respectively, were referred by Dental Department to our Dermatology Department for thinning of hair. History of the present illness revealed hypotrichosis, reduced body hair, peg-shaped teeth with difficulty in chewing [Figure 1 and 2a]. They were intolerant to hot climate with a history of reduced sweating. Examination showed sparse eyebrows, eyelashes, thin, brittle, lusterless scalp hair, sebaceous hyperplasia over the face, frontal bossing, prominent supra-orbital ridges, depressed nasal bridge, thick and prominent lips, mid-face hypoplasia. Skin was dry and wrinkled with no nail dystrophy. Intraoral examination revealed anodontia, microdontia, conical-shaped teeth. Orthopantomogram revealed conical-shaped teeth with reduction in the height of alveolar crest in maxillary and mandibular arches [Figure 2b]. Patients were advised to take frequent sipping of water, emollients for dry skin and 5% topical minoxidil lotion for hair. They were referred to the dental department for implantation of artificial denture.Figure 1: Case#1 - Typical face of ectodermal dysplasiaFigure 2: (a and b) Case#2 - Absence of body hair. Orthopantomography shows conical-shaped teeth with anodontiaCase #3 10 year-old boy came to our department with his parents with a complaint of intolerability of heat. His 4-year-old brother was normal. On examination, brittle, sparse scalp hairs, lack of eyebrows and other body hairs, dry skin, frontal bossing, prominent upper and lower lips were present [Figure 3a]. Intraoral examination showed peg-shaped teeth with spacing between two lateral incisors in both upper and lower jaw. Orthopantomogram revealed multiple missing teeth, peg-shaped teeth [Figure 3b].Figure 3: (a) Case#3 - Lack of eyebrows, sparse lusterless hair. (b) OPG shows microdontia, conical-shaped teeth. OPG = OrthopantomogramCase #4 11 year old boy with no consanguinity presented to us with chewing difficulty and palmoplantar keratoderma for 3 years of age. There was history of premature loss of deciduous and permanent teeth. His two brothers have keratoderma and ichthyosis but no dental abnormalities. Examination revealed palmoplantar keratoderma, ichthyosis over dorsal aspect of hands, feet, knees, trunks and nail dystrophy [Figure 4a and b]. Orthopantomography showed several floating teeth with generalized horizontal bone loss [Figure 4c]. On the basis of history and clinical examination, a diagnosis of Papillon-Lefevre syndrome (PLS), a rare type of ED with hyperkeratosis, has been made. Patient was given oral acitretin at a dose of 0.5 mg/kg body weight after performing liver, renal function tests and complete blood count. He was also prescribed emollient and referred to the dental department for prosthesis to alleviate difficulty in chewing.Figure 4: (a) Case#4 of Papillon-Lefevre syndrome. (b) Case#4 shows planter keratoderma. (c) Case#4 OPG shows periodontitis, some floating teeth. OPG = OrthopantomogramTrichoscopy showed the marked reduction of the follicular openings in all patients except in PLS along with different hair shaft diameter, colour and perifollicular halo [Figure 5a-c].Figure 5: (a) Trichoscopy shows marked reduction in white dots, perifollicular halo (red circle), different hair shaft diameter (Case #1). (b) Trichoscopy shows reduction in white dots, different colour of hair shaft (Case #2). (c) Dermoscopy of body shows complete absence of follicular opening (Case #3)ED exhibits diverse inheritance patterns, including autosomal dominant, autosomal recessive and X-linked inheritance. There are two major types of this condition depending upon the number and functionality of sweat glands: (1) X-linked anhidrotic or hypohidrotic type, (2) hidrotic type, also known as Clouston’s syndrome where teeth, nail and hair have been affected with sparing of sweat glands. Extra-orally fine, sparse, lusterless hair is seen over the scalp along with dry and wrinkled skin, unexplained pyrexia and heat intolerance due to hypo or anhidrosis. There is no mental retardation. The characteristic features of hypo or anhidrotic ED are frontal bossing, sunken cheeks, depressed nasal bridge, thick everted protuberant lips and wrinkled hyperpigmented periorbital skin with a low set of ears. Hypodontia or anodontia of deciduous and permanent dentition associated with conical-shaped teeth with chewing difficulty is the most common oral manifestation.[4] Our 1, 2 and 3 no. patients had involvement of hair, teeth and sweat glands [Table 1]. Three out of four patients presented with chewing difficulty due to abnormal tooth but no patients in our case series have consanguineous parents. These clinical features were supportive in diagnosing hypohidrotic ED. Intraorally missing permanent teeth are most commonly present along with conical crown. Diagnosis of ED is mainly based on family history and clinical manifestation with radiographic examination.[5] On the other hand, PLS, classified as a very rare type of ED, is an autosomal recessive condition related to cathepsin C (CTSC) gene mutation. The first clinical symptoms manifest usually between 1 and 5 years of age as seen in our number 4 patient. The symptoms of PLS are characterized by palmoplantar keratoderma, early-onset periodontitis with a tendency to infection secondary to impaired phagocytosis and chemotaxis of neutrophils. PLS is relatively unique than other types of ED due to periodontitis and palmoplantar keratoderma. The loss of primary teeth starts already at the time of their eruption without any root absorption.[3] Periodontitis does not respond to standard anti-inflammatory treatment and is characterized by alveolar bone destruction and deep periodontal pockets.[6] Diagnosis is mainly based on clinical manifestations and radiographic features. Treatment of PLS patients is symptomatic and often ineffective. Maintenance of oral hygiene, antiseptic mouth rinse and systemic antibiotic therapy is the mainstay of treatment. Early orthodontic and prosthetic therapy is necessary. For the treatment of skin lesions like keratoderma oral retinoids, emollients, keratolytic drugs, salicylic acid derivatives, steroids are most commonly used.Table 1: Presenting and trichoscopic features of patientsED, a rare congenital disorder, often presents to dental departments due to its characteristic oral manifestations, but dermatologists should be aware to diagnose the condition to implement early rehabilitation to improve the quality of life of the patients. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.