A Series of Patients with Genodermatoses in a Reference Service for Rare Diseases: Results from the Brazilian Rare Genomes Project.

BACKGROUND/OBJECTIVES: Genodermatoses are genetic conditions with clinical symptoms manifesting in the skin and adjoining tissues, individually rare but comprising a large and heterogeneous group of disorders that represents 15% of genetic diseases. This article discusses the results of individuals with genodermatoses from a reference center for rare diseases studied through whole genome sequencing conducted by the Brazilian Rare Genomes Project between 2021 and 2023.

METHODS

A retrospective case series with data comprising sex, age at first assessment in the hospital, family history, clinical findings, and molecular results.

RESULTS

Excluding neurofibromatosis type 1, Ehlers-Danlos syndrome and RASopathies are discussed elsewhere. Diagnoses in this work comprised ectodermal dysplasias ( = 6), ichthyosis ( = 4), albinism ( = 4), tuberous sclerosis complex ( = 4), and incontinentia pigmenti ( = 3), in addition to 11 others with individual rare conditions. The sex ratio was 17:16 (M:F), consanguinity was present in 6/33 (18%), and the age at the first evaluation ranged from neonatal to 26 years (median 13.65 years). Negative results were 3/33 (9%), novel variants were 17/41 (41.4%), and 7/30 (23%) presented initially with a double molecular diagnosis, three confirming composed phenotypes.

CONCLUSIONS

Besides reporting 17 novel variants in 14 genes (, , , , , , , , , , , , , and ), the study also identified three atypical clinical presentations due to dual diagnoses, and the c.454C>T variant in the gene, previously reported only in dogs, was, for the first time, confirmed as causative for ichthyosis in humans.