A novel EDA variant that causes X-linked hypohidrotic ectodermal dysplasia in a Chinese family

Hypohidrotic ectodermal dysplasia (HED) is a rare genetic disorder that affects the development of the skin, hair, nails, teeth, and sweat glands. Due to its rarity, there are currently few methods that can be applied to facilitate its diagnosis during the prenatal period. Although a prenatal ultrasonographic examination will detect early signs of the disease, there are few reports on specific prenatal ultrasonographic features of ectodermal dysplasia. Genetic diagnosis can confirm the disease, but the numerous gene variants that cause ectodermal dysplasia have not been fully identified.

Our case was a multiparous woman carrying a single male fetus who underwent a fetal ultrasound examination at 23 weeks of gestation. The examination revealed thin alveolar bone, with no presence of hypoechoic tooth germ tissue in both the upper and lower alveolar bones. The seven-year-old male proband in this family manifested a clinical phenotype of sparse hair and underdeveloped teeth, and trio-based whole-exome sequencing (WES) performed on both parents and the proband revealed a novel and likely pathogenic variant of the EDA gene (NM_001399.4: c.806G > T, p.Gly269Val) associated with X-linked HED (XLHED; OMIM:305100). Based on the results of the fetal ultrasound examination and the results of the proband's genetic testing, the couple ultimately decided to terminate the pregnancy. The DNA of the fetal skin tissue after the induced abortion was extracted for Sanger sequencing, and it was confirmed that the fetus possessed ectodermal dysplasia generated by the afore-mentioned EDA gene mutation.

Our study suggested that prenatal ultrasonography constituted an effective method for screening ectodermal dysplasia during pregnancy. In addition, our findings expanded the range of EDA variants in XLHED patients; and this discovery may now assist potential patients in receiving an accurate diagnosis, allowing them to make appropriate reproductive decisions.