X-linked hypohidrotic ectodermal dysplasia

X-linked hypohidrotic ectodermal dysplasia (XLHED), also known as Christ-Siemens-Touraine syndrome, is the most common form of ectodermal dysplasia. It is caused by pathogenic variants in the EDA gene located on the X chromosome, which encodes the protein ectodysplasin A. This protein plays a critical role in the development of ectodermal structures during embryonic life, including hair, teeth, and sweat glands. Because of its X-linked recessive inheritance, males are typically more severely affected, while female carriers may show mild or variable features. The hallmark clinical triad of XLHED includes hypohidrosis (reduced or absent sweating due to fewer or absent eccrine sweat glands), hypotrichosis (sparse, thin, and lightly pigmented scalp and body hair), and hypodontia or oligodontia (missing teeth, with those present often being conical or peg-shaped). The inability to sweat properly can lead to life-threatening hyperthermia, particularly in infants and young children, as the body cannot regulate temperature effectively. Affected individuals may also have characteristic facial features including frontal bossing, a depressed nasal bridge, prominent lips, and periorbital wrinkling and hyperpigmentation. Dry skin, eczema-like rashes, and reduced mucous gland secretions affecting the eyes, airways, and gastrointestinal tract are also common. Currently, management of XLHED is primarily supportive and symptomatic. Temperature regulation strategies are essential, including avoidance of overheating, access to cooling devices, and environmental modifications. Dental management typically involves early prosthetic rehabilitation with dentures or dental implants to improve feeding, speech, and appearance. Artificial tears and nasal saline may be used for dryness of the eyes and airways. An investigational prenatal and neonatal treatment with a recombinant replacement protein (ER004) targeting the EDA pathway has shown promise in clinical trials, but is not yet approved for routine clinical use. Genetic counseling is recommended for affected families.

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