Cornelia de Lange syndrome in diverse populations

Abstract

Cornelia de Lange syndrome (CdLS) is a dominant multisystemic malformation syndrome due to mutations in 5 genes-NIPBL, SMC1A, HDAC8, SMC3, and RAD21. The characteristic facial dysmorphisms include microcephaly, arched eyebrows, synophrys, short nose with depressed bridge and anteverted nares, long philtrum, thin lips, micrognathia, and hypertrichosis. Most affected individuals have intellectual disability, growth deficiency, and upper limb anomalies. This study looked at individuals from diverse populations with both clinical and molecularly confirmed diagnoses of CdLS by facial analysis technology. Clinical data and images from 246 individuals with CdLS were obtained from 15 countries. This cohort included 49% female patients and ages ranged from infancy to 37 years. Individuals were grouped into ancestry categories of African descent, Asian, Latin American, Middle Eastern, and Caucasian. Across these populations, 14 features showed a statistically significant difference. The most common facial features found in all ancestry groups included synophrys, short nose with anteverted nares, and a long philtrum with thin vermillion of the upper lip. Using facial analysis technology we compared 246 individuals with CdLS to 246 gender/age matched controls and found that sensitivity was equal or greater than 95% for all groups. Specificity was equal or greater than 91%. In conclusion, we present consistent clinical findings from global populations with CdLS while demonstrating how facial analysis technology can be a tool to support accurate diagnoses in the clinical setting. This work, along with prior studies in this arena, will assist in earlier detection, recognition, and treatment of CdLS worldwide.

Clinical and molecular analysis in a cohort of Chinese children with Cornelia de Lange syndrome

“…a Indicates that the incidence of phenotype was statistically significant compared with our cohort. The four other groups (African and African American, Asian, Latin American, and the Middle East) of features data were from the Dowsett et al 14 www.nature.com/scientificreports/ few facial features of with CdLS. Furthermore, P15 had hypertelorism and a broad nasal tip, which is consistent with other reported patients with HDAC8 variants 16 .…”

Rubinstein–Taybi syndrome in diverse populations

“…This work is part of our ongoing series of studies on common human malformation syndromes in populations underrepresented in the medical literature (Dowsett et al, 2019; Kruszka, Addissie, et al, 2017; Kruszka, Porras, Addissie, et al, 2017; Kruszka, Porras, Sobering, et al, 2017; Kruszka et al, 2018; 2020; Muenke, Adeyemo, & Kruszka, 2016).…”

MRNA Transcription, Translation, and Defects in Developmental Cognitive and Behavioral Disorders

“…Mutations in SMC1, SMC3, RAD21, and NIPBL have been reported to lead to Cornelia de Lange syndrome associated with developmental defects in a number of systems (Dowsett et al, 2019).…”