EDA Gene Sequencing Test Details
X-Linked Hypohidrotic Ectodermal Dysplasia (XLHED) is characterized by three cardinal features: hypotrichosis (sparse hair), hypohidrosis (reduced sweating) and hypodontia (absence of teeth) (Wright 2009). Individuals with XLHED often have hair that is thin, slow-growing, and lightly pigmented. Eyebrows may also be sparse or missing. Individuals will also have absent or reduced sweating, which can lead to hypothermic episodes if body temperature is not controlled externally. Teeth can also be affected and are either missing entirely or formed abnormally with delayed eruption timing. The teeth are typically smaller than average with conical crowns. Female carriers can show abnormal patterns of sweat pore distribution and function. Additionally, some degree of hypodontia and mild hypotrichosis can be seen in female carriers (Cambiaghi 2000). Affected individuals may have other features including fragile appearing skin, raspy voice, decreased sebaceous secretions, and abnormal nasal secretions. Typical facial features have been noted in some individuals with XLHED such as frontal bossing, protruding lips, saddle nose and sunken cheeks.Read More...
X-linked hypohidrotic ectodermal dysplasia is inherited in an X-linked manner and caused by variants in the EDA gene. Over 100 variants (including missense, nonsense and splicing) have been identified in individuals with XLHED, but no clear genotype-phenotype correlations have been noted. However, some individuals with isolated dental phenotypes have also been found to have missense variants in EDA (Mikkola 2008).Less
Sequencing of the EDA gene is recommended for males with clinical features of XLHED or females with milder features and/or family history. Pathogenic variants in the EDA gene account for 95% of all cases of XLHED. Sequencing variants are the more common type of variant identified, so reflexive testing from DNA sequencing to deletion/duplication analysis (See EDA MLPA Del/Dup Test page) can be performed. An overlapping phenotype is seen with the autosomal dominant and recessive forms of hypohidrotic ectodermal dysplasia; however, the X-linked form is most common accounting for up to 60% of HED. This should be taken into consideration during a medical evaluation and family history assessment.
This test is performed by Sanger sequencing of the coding regions and splice sites of the EDA gene. This test does not detect large deletions or variants in non-coding regions that could affect gene expression.
Analytical and Clinical Sensitivity
This test is greater than 99.9% accurate in detecting variants in the sequence analyzed. Approximately 95% of males with a clinical diagnosis of X-Linked Hypohidrotic Ectodermal Dysplasia have pathogenic variants in the EDA gene.