RESUMO
Coffin-Siris syndrome (CSS) is a rare multisystemic autosomal dominant disorder. Since 2012, alterations in genes of the SWI/SNF complex were identified as the molecular basis of CSS, studying largely pediatric cohorts. Therefore, there is a lack of information on the phenotype in adulthood, particularly on the clinical outcome in adulthood and associated risks. In an international collaborative effort, data from 35 individuals ≥ 18 years with a molecularly ascertained CSS diagnosis (variants in ARID1B, ARID2, SMARCA4, SMARCB1, SMARCC2, SMARCE1, SOX11, BICRA) using a comprehensive questionnaire was collected. Our results indicate that overweight and obesity are frequent in adults with CSS. Visual impairment, scoliosis, and behavioral anomalies are more prevalent than in published pediatric or mixed cohorts. Cognitive outcomes range from profound intellectual disability (ID) to low normal IQ, with most individuals having moderate ID. The present study describes the first exclusively adult cohort of CSS individuals. We were able to delineate some features of CSS that develop over time and have therefore been underrepresented in previously reported largely pediatric cohorts, and provide recommendations for follow-up.
Assuntos
Anormalidades Múltiplas , Face/anormalidades , Deformidades Congênitas da Mão , Deficiência Intelectual , Micrognatismo , Adulto , Humanos , Criança , Deficiência Intelectual/genética , Deficiência Intelectual/diagnóstico , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/diagnóstico , Micrognatismo/genética , Micrognatismo/diagnóstico , Deformidades Congênitas da Mão/genética , Pescoço/anormalidades , Fenótipo , DNA Helicases/genética , Proteínas Nucleares/genética , Fatores de Transcrição/genética , Proteínas Cromossômicas não Histona/genética , Proteínas de Ligação a DNA/genéticaRESUMO
Clinical geneticists and syndromologists have traditionally focused on identifying syndromes in children. However, there is a growing acknowledgment of the need to describe adult phenotypes. This article provides an overview of the evolving phenotypes of rare genetic syndromes into adulthood, elucidating its challenges, opportunities, and future perspectives. The clinical phenotypes of four adults with Costello syndrome are described to illustrate these aspects. Phenotypic and genotypic data from four individuals broaden the spectrum of Costello syndrome in adulthood and highlight the high variability in neurocognitive outcome. The clinical data align with previous findings and established genotype-phenotype correlations. Interestingly, two individuals presented with recurrent cancers (bladder cancer and neuroblastoma). Further studies are imperative to provide reliable information for counselling and management to enable comprehensive understanding of the evolving features of rare syndromic diseases and special health issues into adulthood.