A 30-year-old Hispanic woman presents with her 1-year-old son, concerned that he has only small amounts of thin, wispy hair on his head and has none anywhere else on his body. She notes that he does not yet have any teeth, but has a large forehead and ears. He has been irritable and crying for the past day. She reveals a personal history of very high body temperature at times during the summer and says she customarily stays indoors with the air conditioning on, especially in the summer. On physical examination, she has sparse hair on her scalp and eyebrows, as well as eczematous patches on her bilateral lower extremities.
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Hypohidrotic ectodermal dysplasia is a genetic disorder commonly inherited in an X-linked pattern due to mutations of the EDA gene, which codes the protein ectodysplasin A.1
Patients typically present during childhood with the triad of hypohidrosis, hypodontia, and hypotrichosis, along with other prominent features of the disease.1 The patient’s reduced ability to sweat can lead to abnormalities of body temperature regulation.2 Scant amounts of hair may be present on the patient’s body, and there is typically delayed and abnormal dental development.1
Diagnosis is made clinically based on multiple physical manifestations of the condition.1 This genetic disease can generally be detected during early childhood. Scant, light-colored hair is usually present on the scalp and body.1 High body temperatures generally cause babies to cry and become irritable and suggest a lack of appropriate cooling mechanisms.1 If this is suspected, the function of sweat glands can be evaluated in the office. Covering skin with iodine and raising the body temperature may reveal reduction in function of sweat glands; a patient with normally functioning sweat glands will sweat, which changes the color of the iodine from yellow to blue.1 Absence of this color change indicates dysfunction of the sweat glands. Facial abnormalities may also be present, including frontal bossing, saddle nose, thick lips, and large ears. These abnormal facies may be mistaken for the manifestations of congenital syphilis.2,3 Wrinkled or hyperpigmented skin may be present in the periorbital area.1 Dental examination reveals few small, conical teeth.1 Patients may also have patches of eczema and dry, peeling skin.3 Some patients may have respiratory difficulties, including frequent upper respiratory infections or asthma due to thick nasal secretions.2,3 Postpregnancy attempts at breast-feeding may reveal mammary gland hypoplasia.1
Hypohidrotic ectodermal dysplasia is just one of several ectodermal dysplasias, an array of syndromes that involve abnormal development of ectodermal tissues, including hair, teeth, and others. However, this specific disorder can often be distinguished based on careful physical examination.
Differential diagnosis includes Schöpf-Schulz-Passarge syndrome, odonto-onychodermal dysplasia syndrome, Witkop tooth and nail syndrome, Trichodento-osseous syndrome, and Clouston syndrome.1,2 Unlike several of these syndromes, hypohidrotic ectodermal dysplasia lacks significant nail abnormalities.1 Clouston syndrome, or hidrotic ectodermal dysplasia, presents similarly to hypohidrotic ectodermal dysplasia but lacks sweat gland involvement.2
The most common form of hypohidrotic ectodermal dysplasia is Christ-Siemens-Touraine syndrome,2 which demonstrates X-linked inheritance. Autosomal dominant and autosomal recessive variants also exist.1 Therefore, genetic testing may be beneficial in family members for appropriate management. When evaluating patients for hypohidrotic ectodermal dysplasia, it is important to bear in mind that patients may exhibit mosaicism.1 Additionally, if evaluating a patient with X-linked hypohidrotic ectodermal dysplasia, it is important to note that women may not have full involvement.4 In this case report, the child had much more severe involvement when compared with his mother.
As mentioned earlier, mutations leading to hypohidrotic ectodermal dysplasia usually affect ectodysplasin A (EDA), which functions in the tumor necrosis factor signaling pathway and is important in organ development.5 The EDA, EDA receptor (EDAR), and EDAR-associated death domain (EDARADD) genes that correspond to a ligand, a receptor, and an adapter, respectively, have all been implicated in association with this disease.1,2,5 There are many more mutations of the EDA gene that cause hypohidrotic ectodermal dysplasia than mutations of the EDAR or EDARADD genes.5 Interestingly, there are also many different mutations in EDA that can lead to a similar phenotype; however, certain mutations of EDA can instead lead to dental dysgenesis without the accompanying syndrome.5 Most mutations leading to hypohidrotic ectodermal dysplasia are null mutations, although missense mutations may occur also.5
Treatment involves managing each component of this condition. Currently, no cure is available, although ongoing clinical trials are evaluating the viability of the EDI200 protein in patients with hypohidrotic ectodermal dysplasia. In order to manage hypohidrosis, patients should inhabit a cool environment to minimize risk of hyperthermia.1 Cosmetic appearance of hypotrichosis can be improved with the use of wigs or topical minoxidil.1,2 From a dental perspective, patients may require dental implants or dentures, with regular dental examinations and dental radiographs.1 Oral lubrication may be necessary in certain patients to reduce risk of dental caries.1
Complications of hypohidrotic ectodermal dysplasia should be managed simultaneously. For example, eczematous dermatitis should be managed with topical corticosteroids.3 Humidifiers can be used to loosen nasal secretions, and removal of mucus can be performed with suction.1
Patients should also undergo evaluation by a medical geneticist in order to determine implications of disease for future progeny. Family members may also decide to undergo genetic evaluation to determine carrier status. Future directions for treatment of this disease include gene therapy targeting downstream genes, as well as research to elucidate upstream pathways in the EDA sequence.5
In our case, the mother and child both had many features indicative of hypohidrotic ectodermal dysplasia. Genetic testing revealed that the mother was heterozygous for an X-linked mutation of the EDA gene, whereas the child was homozygous for this mutation, which is consistent with the clinical presentation. They were both treated with topical corticosteroids for the eczematous dermatitis associated with the disease.
Yasmin Qaseem, BS, BA, is a medical student and Maura Holcomb, MD, is a dermatology resident at Baylor College of Medicine in Houston.
- Wright JT, Grange DK, Richter MK. Hypohidrotic ectodermal dysplasia. GeneReviews website. http://www.ncbi.nlm.nih.gov/books/NBK1112. Updated May 15, 2014. Accessed April 25, 2016.
- Anoop TM, Simi S, Mini PN, et al. Hypohydrotic ectodermal dysplasia. J Assoc Physicians India. 2008;56:268-270.
- Lu PD, Schaffer JV. Hypohidrotic ectodermal dysplasia. Dermatol Online J. 2008 15;14(10):22.
- Bansal M, Manchanda K, Pandey SS. Hypohidrotic ectodermal dysplasia. Int J Trichology. 2012;4(3):167-168.
- Mikkola ML. Molecular aspects of hypohidrotic ectodermal dysplasia. Am J Med Genet A. 2009;149A(9):2031-2036.