Hypohidrotic ectodermal dysplasia

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Hypohidrotic ectodermal dysplasia is one of more than 100 types of ectodermal dysplasia. Starting before birth, these disorders result in the abnormal development of ectodermal tissues, particularly the skin, hair, nails, teeth, and sweat glands.

Most people with hypohidrotic ectodermal dysplasia have a reduced ability to sweat (hypohidrosis) because they have fewer sweat glands than normal or their sweat glands do not function properly. Sweating is a major way that the body controls its temperature; as sweat evaporates from the skin, it cools the body. Reduced sweating can lead to a dangerously high body temperature (hyperthermia), particularly in hot weather. In some cases, hyperthermia can cause life-threatening health problems.

Affected individuals tend to have sparse scalp and body hair (hypotrichosis). The hair is often light-colored, brittle, and slow-growing. Hypohidrotic ectodermal dysplasia is also characterized by several missing teeth (hypodontia) or teeth that are malformed. The teeth that are present erupt from the gums later than usual and are frequently small and pointed.

Some people with hypohidrotic ectodermal dysplasia have distinctive facial features, including a prominent forehead, thick lips, and a flattened bridge of the nose. Additional features of this condition can include thin, wrinkled, and dark-colored skin around the eyes; chronic skin problems such as eczema; and a bad-smelling discharge from the nostrils (ozena).

Intellectual ability and growth are typically normal in people with hypohidrotic ectodermal dysplasia.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Hypohidrotic ectodermal dysplasia is a genetic condition that can result from mutations in one of several genes. These include EDA, EDAR, EDARADD, and WNT10A. EDA gene mutations are the most common cause of the disorder, accounting for more than half of all cases. EDAR, EDARADD, and WNT10A gene mutations each account for a smaller percentage of cases. In about 10 percent of people with hypohidrotic ectodermal dysplasia, the genetic cause is unknown.

The EDA, EDAR, and EDARADD genes provide instructions for making proteins that work together during embryonic development. These proteins form part of a signaling pathway that is critical for the interaction between two cell layers, the ectoderm and the mesoderm. In the early embryo, these cell layers form the basis for many of the body's organs and tissues. Ectoderm-mesoderm interactions are essential for the formation of several structures that arise from the ectoderm, including the skin, hair, nails, teeth, and sweat glands.

Mutations in the EDA, EDAR, or EDARADD gene prevent normal interactions between the ectoderm and the mesoderm, which impairs the normal development of skin, hair, nails, teeth, and sweat glands. Mutations in any of these three genes lead to the major signs and symptoms of hypohidrotic ectodermal dysplasia described above.

The WNT10A gene provides instructions for making a protein that is part of a different signaling pathway known as Wnt signaling. Wnt signaling controls the activity of certain genes and regulates the interactions between cells during embryonic development. Signaling involving the WNT10A protein is critical for the development of ectodermal structures, particularly the teeth. The WNT10A gene mutations that cause hypohidrotic ectodermal dysplasia impair the protein's function, which disrupts the development of teeth and other structures that arise from the ectodermal cell layer.

When hypohidrotic ectodermal dysplasia results from WNT10A gene mutations, its features are more variable than when the condition is caused by mutations in the EDA, EDAR, or EDARADD gene. Signs and symptoms range from mild to severe, and mutations in the WNT10A gene are more likely to cause all of the permanent (adult) teeth to be missing.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

Hypohidrotic ectodermal dysplasia has several different inheritance patterns. Most cases are inherited in an X-linked pattern and are caused by mutations in the EDA gene. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females, who have two copies of the X chromosome, one altered copy of the gene in each cell often leads to less severe features of the condition. Signs and symptoms can include a few missing or abnormal teeth, sparse hair, and mild problems with sweat gland function. However, some females with one copy of the mutated gene have more severe features of this disorder.

Less commonly, hypohidrotic ectodermal dysplasia has an autosomal dominant or autosomal recessive pattern of inheritance. Mutations in the EDAR, EDARADD, or WNT10A gene can cause either autosomal dominant or autosomal recessive hypohidrotic ectodermal dysplasia.

Autosomal dominant inheritance means one copy of the altered gene in each cell is sufficient to cause the disorder. Some affected individuals inherit the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.

Autosomal recessive inheritance means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene. Some mutation carriers have mild signs and symptoms of hypohidrotic ectodermal dysplasia, including a somewhat reduced ability to sweat and less severe dental abnormalities.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Hypohidrotic ectodermal dysplasia is the most common form of ectodermal dysplasia. It is estimated to occur in 1 in 20,000 newborns worldwide.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormal dental morphology · Very frequent (99-80%)

An abnormality of the morphology of the tooth.

Dry skin · Very frequent (99-80%)

Skin characterized by the lack of natural or normal moisture.

Generalized hypotrichosis · Very frequent (99-80%)

Reduced or lacking hair growth in a generalized distribution.

Hypodontia · Very frequent (99-80%)

The absence of five or less teeth from the normal series by a failure to develop.

Hypohidrosis · Very frequent (99-80%)

Abnormally diminished capacity to sweat.

Sparse body hair · Very frequent (99-80%)

Sparseness of the body hair.

Sparse scalp hair · Very frequent (99-80%)

Decreased number of hairs per unit area of skin of the scalp.

Thick vermilion border · Very frequent (99-80%)

Increased width of the skin of vermilion border region of upper lip.

Other findings in the same source

From: Orphanet

Additional reported features include Abnormality of temperature regulation (Frequent (79-30%)); Anodontia (Frequent (79-30%)); Aplasia/Hypoplasia of the eyebrow (Frequent (79-30%)); Asthma (Frequent (79-30%)); Brittle hair (Frequent (79-30%)); Conical tooth (Frequent (79-30%)); Delayed eruption of teeth (Frequent (79-30%)); Depressed nasal bridge (Frequent (79-30%)); Eczematoid dermatitis (Frequent (79-30%)); Feeding difficulties (Frequent (79-30%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Hypohidrotic ectodermal dysplasia is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Hypohidrotic ectodermal dysplasia. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.