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Indian J Dermatol
Indian J Dermatol
IJD
Indian J Dermatol
Indian Journal of Dermatology
0019-5154
1998-3611
Wolters Kluwer - Medknow India

IJD-69-366d
10.4103/ijd.ijd_712_23
E–IJD®: Quiz
Sparse Hair, Missing Teeth, Dry Skin: An Uncommon but Classic Condition
Konda Deepthi
Reddy Mounika 1
From the Department of Dermatology, All India Institute of Medical Sciences (AIIMS), Bibinagar, Telangana, India
1 Department of Paediatrics, All India Institute of Medical Sciences (AIIMS), Bibinagar, Telangana, India
Address for correspondence: Dr. Deepthi Konda, Department of Dermatology, All India Institute of Medical Sciences (AIIMS), Bibinagar, Telangana – 508 126, India. E-mail: knddeepthi@gmail.com
Jul-Aug 2024
19 8 2024
69 4 366366
7 2023
8 2023
Copyright: © 2024 Indian Journal of Dermatology
2024
https://creativecommons.org/licenses/by-nc-sa/4.0/ This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.
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pmcA 12-year-old girl was brought to dermatology outpatient department with the absence of sweating and severe heat intolerance since one year of life. She was born to a non-consanguineous couple, and there were no similar complaints in the other family members. Physical examination revealed sparse scalp hair especially over the temporo-parietal areas [Figure 1], few to absent eyebrows and eyelashes, mild frontal bossing, periorbital hyperpigmentation and protruding lips. Intraoral examination showed four peg-shaped teeth [Figure 2] and the absence of remaining teeth. Cutaneous examination revealed generalised dryness and flat, brown-coloured thin ichthyotic scales on both the shins [Figure 3]. Nails were normal on examination. Patient had an average intelligence level. Complete physical examination of both the parents and sibling (female) was normal. However, genetic analysis could not be done in the patient and her parents due to financial constraints.

Figure 1 Sparse, dry, brittle hair mainly over the temporo-parietal area

Figure 2 Four peg-shaped teeth with the absence of remaining teeth

Figure 3 Dry skin and ichthyosis on both the shins

What is the Diagnosis?

Hypohidrotic ectodermal dysplasia.

Discussion

Ectodermal dysplasia (ED), first described by Thurnam in 1848, includes a group of rare hereditary disorders that occur due to disturbances in structures of ectoderm in developing embryo.[1] There are around 100 types of ED, of which X-linked recessive hypohidrotic ED (Christ-Siemens-Tourine syndrome) and autosomal dominant hidrotic ED (Clouston’s syndrome) are the most common variants.[2] Eds are uncommon heterogenous disorders with abnormalities in ectodermal components with an incidence of about 7 in 10,000 live births.[3] Based on the presence or absence of sweating, ED is broadly categorised into hypohidrotic and hidrotic types.

The most common inheritance pattern (95%) of hypohidrotic ectodermal dysplasia is X-linked recessive and thus predominantly seen in males. The remaining 5% are inherited by autosomal recessive and autosomal dominant pattern. However, in rare cases, hypohidrotic ectodermal dysplasia might occur due to de novo mutation.[4] In our case, only the girl was affected and none of her parents or the female sibling showed any clinical features of ED. This raises the possibility of autosomal recessive mode of inheritance with heterozygous pathogenic variant in EDAR, EDARADD, or WNT10A in the parents. X-linked hypohidrotic ectodermal dysplasia (HED) is caused by mutations in the ectodysplasin gene (EDA), located at Xq12–q13.1, whereas the autosomal recessive and autosomal dominant HED is due to a mutation in ectodysplasin A receptor (EDAR) and EDAR-associated death domain (EDARADD) genes, respectively. The EDA gene encodes the transmembrane type II protein ectodysplasin which along with its receptor EDAR is involved in the interaction of ectoderm–mesoderm and thus plays an important role in ectodermal morphogenesis, odontogenesis, and organogenesis of the developing embryo.[2]

HED is characterised by the classical triad of hypotrichosis, hypohidrosis and hypodontia as seen in our case. Hypohidrosis, due to hypoplasia of sweat glands, can lead to generalised dryness, heat intolerance and hyperthermia. Glandular hypoplasia also leads to decreased secretions in respiratory tract and middle ear leading to recurrent infections. The affected individual shows periorbital hyperpigmentation, periorbital wrinkling, frontal bossing, depressed nasal bridge, a prominent chin, protuberant lips and decreased vertical dimension of lower face (due to hypodontia and lack of alveolar ridge).[5] Hidrotic ED has hypodontia and hypotrichosis similar to that of hypohidrotic Ed, but sweating is normal and has nail deformities.

The diagnosis of hypohidrotic ectodermal dysplasia is usually made based on clinical features. However, genetic testing for the genes related to this condition such as EDA, EDAR and EDARADD can be done for confirmation. Management of hypohidrotic Ed is mainly symptomatic and requires a collective approach by dermatologist, paediatrician, dental specialist, and psychologist. Due to their inability to sweat and the risk of hyperthermia, patients with HED are advised to avoid prolonged sun exposure due to which they can develop deficiency of Vitamin D levels. However, serum levels of Vitamin D were within normal limits in our patient. So, Vitamin D supplementation was not advised. Therapeutic trials with gene therapy are being conducted to improve the symptoms of patients with HED. Schneider et al.[6] reported successful treatment of X-linked ED by intra-amniotic administration of the Fc-EDA (ectodysplasin-A1 replacement protein), to three affected male foetuses. Postnatally, they were able to sweat normally and had not developed X-linked HED-related hyperthermia or respiratory illnesses, although correction of the deciduous dentition was not achieved. Fc-EDA has been shown to bind specifically to the EDA-A1 receptor (EDAR) and activate the signalling pathway that leads to normal ectodermal development. Genetic counselling and prenatal analysis can help in preventing the development of ectodermal dysplasia.

Learning Points

Hypohidrotic ectodermal dysplasia is usually caused by mutations in the ectodysplasin gene (EDA), has X-linked recessive inheritance, and is commonly seen in boys.

It can also occur due to autosomal recessive and autosomal dominant inheritance, in which case, girls too can be affected.

Hypohidrotic ectodermal dysplasia is characterised by the classical triad of hypotrichosis, hypohidrosis and hypodontia along with periorbital hyperpigmentation, wrinkling, frontal bossing, depressed nasal bridge, a prominent chin and protuberant lips.

Hidrotic ED has hypodontia and hypotrichosis similar to that of hypohidrotic ED, but sweating is normal and has nail deformities.

Diagnosis is usually clinical, and management is multidisciplinary.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.
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2 Kumar J Ahmed A Hussain T Kumar D Aslams T Appearance says it all;A rare case of hypohidrotic ectodermal dysplasia J Ayub Med Coll Abbottabad 2022 34 895 7 36566424
3 Vasconcelos Carvalho M Romero Souto de Sousa J Paiva Correa de Melo F Fonseca Faro T Nunes Santos AC Carvalho S Hypohidrotic and hidrotic ectodermal dysplasia: A report of two cases Dermatol Online J 2013 19 18985 24010518
4 Al-Araimi M Hamza N Al Hosni A Al Mazrooey H A first case report of hypohidrotic ectodermal dysplasia from Oman Clin Case Rep 2020 8 716 8 32274043
5 Chappidi V Voulligonda D Bhogavaram B Reddy PK Ectodermal dysplasia: Report of two cases in a family and literature review J Family Med Prim Care 2019 8 1263 5 31041288
6 Schneider H Faschingbauer F Schuepbach-Mallepell S Korber I Wohlfart S Dick A Prenatal correction of X-linked hypohidrotic ectodermal dysplasia N Engl J Med 2018 378 1604 10 29694819
