SNP Shot: Genomic Insights

Hypohidrotic ectodermal dysplasia is one of over 100 types of ectodermal dysplasias. These disorders, present from before birth, disrupt the normal development of ectodermal tissues, specifically affecting the skin, hair, nails, teeth, and sweat glands.

A common characteristic of hypohidrotic ectodermal dysplasia is a reduced ability to sweat (hypohidrosis), stemming from fewer or improperly functioning sweat glands. Because sweating is critical for body temperature regulation (cooling the body as sweat evaporates), reduced sweating can cause dangerously high body temperature (hyperthermia), especially in hot environments. Severe hyperthermia can lead to life-threatening complications.

Individuals with this condition often exhibit sparse scalp and body hair (hypotrichosis). This hair is frequently light-colored, fragile, and grows slowly. Missing teeth (hypodontia) or malformed teeth are also hallmarks of hypohidrotic ectodermal dysplasia. Existing teeth may erupt later than usual and are often small and pointed.

Distinctive facial features, such as a prominent forehead, thick lips, and a flattened nasal bridge, may be present in some individuals with hypohidrotic ectodermal dysplasia. Other possible features include thin, wrinkled, and dark skin around the eyes; chronic skin problems like eczema; and a foul-smelling nasal discharge (ozena).

Typically, intellectual ability and growth are within the normal range for individuals with hypohidrotic ectodermal dysplasia.

Inheritance:

Hypohidrotic ectodermal dysplasia can be inherited in several ways. The majority of cases follow an X-linked inheritance pattern and are caused by mutations in the EDA gene. X-linked inheritance occurs when the disease-causing mutated gene resides on the X chromosome (one of the sex chromosomes). Males, possessing only one X chromosome, will develop the condition if they inherit one altered copy of the gene. Females, with two X chromosomes, often experience milder symptoms with one altered gene copy, such as a few missing or abnormal teeth, sparse hair, and mild sweat gland issues. However, some females with one copy of the mutated gene can exhibit more severe symptoms. Less commonly, hypohidrotic ectodermal dysplasia can be inherited in an autosomal dominant or autosomal recessive pattern. Mutations in the EDAR, EDARADD, or WNT10A genes can cause either autosomal dominant or autosomal recessive hypohidrotic ectodermal dysplasia.

Autosomal dominant inheritance requires only one altered gene copy in each cell to cause the disorder. The mutation can be inherited from an affected parent, or it can arise as a new mutation in the gene in individuals with no family history of the condition.

Autosomal recessive inheritance necessitates that both copies of the gene in each cell carry mutations. In this scenario, the parents of an affected individual each carry one copy of the mutated gene. Some of these carriers might display mild symptoms of hypohidrotic ectodermal dysplasia, such as slightly reduced sweating ability and less severe dental abnormalities.