Congenital Nail Disorders among Children with Suspected Ectodermal Dysplasias

We report on a cohort of 204 children referred between January 2017 and January 2022 to the German Center for Ectodermal Dysplasias, Erlangen. The most frequent reasons for referral were tooth malformations and lack of multiple teeth leading to the suspicion of an ectodermal dysplasia. Many patients also suffered from being unable to perspire. Nail abnormalities, in contrast, represented a much rarer finding, albeit the impact on some individuals was large. As ectodermal dysplasias are congenital genetic conditions affecting the development and/or homeostasis of two or more ectodermal derivatives, including hair, teeth, nails, and certain glands, we analyzed congenital nail disorders detected in these patients. Dystrophic or otherwise abnormal nails were evident in 17 of 18 subjects with pathogenic WNT10A or GJB6 variants but in none of 161 children with EDA variants underlying X-linked hypohidrotic ectodermal dysplasia. However, 2 of 17 children who carry mutations in EDAR or EDARADD, two other genes involved in the ectodysplasin A signaling pathway, showed nail abnormalities, such as brittle or hypoplastic nails. TP63 variants were regularly associated with nail disorders. In one girl, anonychia congenita caused by a compound heterozygous variant of the R-spondin-4 gene (RSPO4) was diagnosed. Thus, nail dysplasia is rarer among patients with ectodermal dysplasia than commonly thought.

Automated summary

A cohort of 204 children referred to the German Center for Ectodermal Dysplasias, Erlangen between January 2017 and January 2022 were analyzed. The most common reasons for referral were tooth malformations and missing teeth, indicating a possible ectodermal dysplasia. Sweating abnormalities were also observed in many patients. Nail abnormalities were less frequent but still had a significant impact on some individuals. Nail disorders were found in subjects with pathogenic WNT10A or GJB6 variants, as well as in children with mutations in EDAR or EDARADD genes involved in the ectodysplasin A signaling pathway. TP63 variants were regularly associated with nail disorders. A case of anonychia congenita caused by a compound heterozygous variant in the RSPO4 gene was also diagnosed. Overall, nail dysplasia is less common among patients with ectodermal dysplasia than previously thought.