The Clinical Research Of Cornelia De Lange Syndrome In Children

[Objective] To retrospectively analyze the clinical characteristics and genetic variations of Cornelia de Lange syndrome(Cd LS)patients,and to explore the clinical phenotype spectrum and gene spectrum of Cd LS,and to provide experience for further diagnosis and treatment of Cd LS in children.[Methods] The objects who were referred to our hospital from January 2011 to December 2018 and diagnosed with Cd LS were included.Their clinical data were collected,such as gender,age,birth history,clinical symptoms,craniofacial features,limb features,height and weight,and laboratory examinations.The phenotypes of this cohort patients were summarized and compared the differences between this cohort and other four cohorts.Targeted panel sequencing was performed for the probands,and the variants were subsequently validated by Sanger sequencing.[Results] A total of 12 patients were included in the study,including 8 males(66.67%)and 4 females(33.33%),ranging from 0.25 to 10.17 years old,with a median age of 3.625 years old.The patients were scored using clinical diagnostic criteria,9 cases(75.00%)with >11 points.Among the typical facial features of Cd LS,all the 12 patients showed long eyelashes,and except case 6,other 11 cases had thick eyebrows and arched eyebrows.Skeletal malformations were mainly mild limb abnormalities,including small hands(83.33%),the 5th finger clinodactyly or short(66.67%).In this cohort,the frequencies of male cryptorchidism,congenital heart disease and renal abnormalities were 62.50%,50.00% and 16.67%,respectively,and 25.00% had hearing abnormalities,16.67% had otitis media in the patients.The phenotypes of this cohort and other four cohorts(Africa and Africa American,Asia,Latin America and the Middle East)were compared.It was found that the frequencies of synophrys,long eyelashes,Long philtrum,ptosis,cleft palate,hypertrichiasis were statistically significant,and further analysis revealed that our cohort had lower frequency of synophrys than Latin American cohort;our cohort had lower frequency of hypertrichiasis than the African cohort and Middle East cohort.All the 12 patients were performed molecular diagnoses,12 gene variations were identified,which were involved in 3 genes,including NIPBL(10 cases),SMC1A(1 case),RAD21(1 case).[Conclusion] The clinical manifestations of the patients in this cohort were basically consistent with other ethnicities,however,several clinical features have different frequencies.Genetic sequencing and analysis identified 12 deleterious variants.Variants in NIPBL gene were the most common cause of Cd LS in our cohort.This study extended the gene spectrum and phenotype spectrum of Cd LS.