Background: Pathogenic variants in KITLG, a crucial protein involved in pigmentation and neural crest cell migration, cause non-syndromic hearing loss, Waardenburg syndrome type 2, familial progressive hyperpigmentation and familial progressive hyper- and hypopigmentation, all of which are inherited in an autosomal dominant manner. Objectives: To describe the genotypic and clinical spectrum of biallelic KITLG-variants. Methods: We used a genotype-first approach through the GeneMatcher data sharing platform to collect individuals with biallelic KITLG variants and reviewed the literature for overlapping reports. Results: We describe the first case series with biallelic KITLG variants; we expand the known hypomelanosis spectrum to include a ‘sock-and-glove-like’, symmetric distribution, progressive repigmentation and generalized hypomelanosis. We speculate that KITLG biallelic loss-of-function variants cause generalized hypomelanosis, whilst variants with residual function lead to a variable auditory-pigmentary disorder mostly reminiscent of Waardenburg syndrome type 2 or piebaldism. Conclusions: We provide consolidating evidence that biallelic KITLG variants cause a distinct auditory-pigmentary disorder. We evidence a significant clinical variability, similar to the one previously observed in KIT-related piebaldism.
|Number of pages||6|
|Journal||Journal of the European Academy of Dermatology and Venereology|
|Publication status||Published - 09-2022|
All Science Journal Classification (ASJC) codes
- Infectious Diseases