Vitiligo em crianças: uma revisão de classificação, hipóteses sobre patogênese e tratamento Vitiligo in children: a review of classification, hypotheses of pathogenesis and treatment

Vitiligo é um achado dermatológico relativamente comum, observado desde a Antiguidade. A doença caracteriza-se por despigmentação da pele, com perda de melanócitos ao exame histológico. Diversos fenótipos clínicos resultam em diferentes graus de morbidade. A causa do vitiligo ainda é desconhecida e a etiologia mais provável parece ser auto-imune. O tratamento é difícil e várias alternativas mostram um potencial terapêutico significativo. Nesta revisão, abordaremos a classificação do vitiligo na infância, as hipóteses sobre a patogênese e o tratamento.Vitiligo is a relatively common dermatologic finding and one that has been observed since ancient times. Depigmentation of the skin, with loss of melanocytes on histology characterizes this disorder. A range of clinical phenotypes lead to varying degrees of morbidity. The cause of vitiligo remains unknown, although an autoimmune pathogenesis seems most likely. Treatment also remains difficult. A number of new therapies show significant potential. In this review, we will focus on the classification of childhood vitiligo, hypotheses of pathogenesis and treatment

De Novo Truncating Variants in ASXL2 Are Associated with a Unique and Recognizable Clinical Phenotype

The ASXL genes (ASXL1, ASXL2, and ASXL3) participate in body patterning during embryogenesis and encode proteins involved in epigenetic regulation and assembly of transcription factors to specific genomic loci. Germline de novo truncating variants in ASXL1 and ASXL3 have been respectively implicated in causing Bohring-Opitz and Bainbridge-Ropers syndromes, which result in overlapping features of severe intellectual disability and dysmorphic features. ASXL2 has not yet been associated with a human Mendelian disorder. In this study, we performed whole-exome sequencing in six unrelated probands with developmental delay, macrocephaly, and dysmorphic features. All six had de novo truncating variants in ASXL2. A careful review enabled the recognition of a specific phenotype consisting of macrocephaly, prominent eyes, arched eyebrows, hypertelorism, a glabellar nevus flammeus, neonatal feeding difficulties, hypotonia, and developmental disabilities. Although overlapping features with Bohring-Opitz and Bainbridge-Ropers syndromes exist, features that distinguish the ASXL2-associated condition from ASXL1- and ASXL3-related disorders are macrocephaly, absence of growth retardation, and more variability in the degree of intellectual disabilities. We were also able to demonstrate with mRNA studies that these variants are likely to exert a dominant-negative effect, given that both alleles are expressed in blood and the mutated ASXL2 transcripts escape nonsense-mediated decay. In conclusion, de novo truncating variants in ASXL2 underlie a neurodevelopmental syndrome with a clinically recognizable phenotype. This report expands the germline disorders that are linked to the ASXL genes