RESUMEN
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.
Asunto(s)
Anomalías Múltiples , Cara/anomalías , Deformidades Congénitas de la Mano , Discapacidad Intelectual , Micrognatismo , Adulto , Humanos , Niño , Discapacidad Intelectual/genética , Discapacidad Intelectual/diagnóstico , Anomalías Múltiples/genética , Anomalías Múltiples/diagnóstico , Micrognatismo/genética , Micrognatismo/diagnóstico , Deformidades Congénitas de la Mano/genética , Cuello/anomalías , Fenotipo , ADN Helicasas/genética , Proteínas Nucleares/genética , Factores de Transcripción/genética , Proteínas Cromosómicas no Histona/genética , Proteínas de Unión al ADN/genéticaRESUMEN
BACKGROUND: Cornelia de Lange syndrome (CdLS) is a rare polymalformative genetic disorder with multisystemic involvement. Despite numerous clinical and molecular studies, the specific evaluation of the quality of life (QoL) and its relationship with syndrome-specific risk factors has not been explored. METHODS: The QoL of 33 individuals diagnosed with CdLS, aged between 4 and 21 years, was assessed using the Kidslife questionnaire. Specifically, the influence of 14 risk factors on overall QoL and 8 of its domains was analyzed. RESULTS: The study revealed below-median QoL (45.3 percentile), with the most affected domains being physical well-being, personal development, and self-determination. When classifying patients based on their QoL and affected domains, variants in the NIPBL gene, clinical scores ≥11, and severe behavioral and communication issues were found to be the main risk factors. CONCLUSIONS: We emphasize the need for a comprehensive approach to CdLS that encompasses clinical, molecular, psychosocial, and emotional aspects. The "Kidslife questionnaire" proved to be a useful tool for evaluating QoL, risk factors, and the effectiveness of implemented strategies. In this study, we underscore the importance of implementing corrective measures to improve the clinical score. Furthermore, we highlight the necessity of applying specific therapies for behavioral problems after ruling out underlying causes such as pain or gastroesophageal reflux and implementing measures that facilitate communication and promote social interaction.