Study On Screening, Diagnosis And Intellectual Development Status In Children With Chromosome 22q11 Deletion Syndrome

Chromosome 22q11deletion syndrome(hereafter 22q11 DS),which is one of the most common genetic syndrome causing intellectual disability,occurs in about 1:4000 live births and arises from a 1.5 to 3.0 Mb hemizygous microdeletion on the long(q) arm of chromosome 22.Its clinical presentation is quite variable;it usually involves multiple systems or oragns,affects the patients' physical and mental health and results in serious suffering and burden of the family and society.Early screening,diagnosis and follow-up,leading to promotion of special education,would improve the quality of life in children with 22q11 DS,which is sufficiently significant to benefit for both the family and society.In this study,the application of a robust,fast and accurate real-time Polymerase Chain Reaction(RT-PCR) based assay using SYBR(?) Green I dye was identified,that is capable of screening for copynumber alterations in genomic DNA in 22q11 DS.Area under the ROC curve(AUC) of this RT-PCR was 0.995,which was significantly greater than the AUC value 0.5,indicating high diagnositic significance.The best cut-off value was explored and the corrected gene dosage TUPLE1/G6PDH=0.79 was validated to achieve 100%sensitivity and 94.2%specificity.Furthermore,by increasing the number of primers in the 22q11 deleted region,another two atypical microdeletion patients were detected,and thus the related information of deletion breakpoints and the length of the deletion were collected as well,which would be beneficial in further study of the relationship between the genotype and clinical phenotype.This study was the first time in China to relatively quantify the performance of various clinical criteria—and their combinations which could be helpful in predicting the high risk for 22q11 DS.The common reported features,including dysmorphic facies, congenital heart diseases,immune defects,endocrine abnormalities,developmental delay,cognitive and behavioral problems were comprehensively evulated.Syndromic heart defects which combine heart defects and at least another two extracardiac features yielded highest discriminant ability(DA) value,considering as the most optimal general predictor of 22q11 DS;besides,Logistic regression were used and indicated that the single best predictors of22q11 DS were immune defects,global dysmorphic facial pattern and congenital heart diseases,which formed the regression equation:Y= -8.278+2.240x1+4.317x2+4.164x3,P=exp(y)/[1+exp(y)],to help guide clinicians in brief clinical encounters to identify patients as early as possible and improve the detection rate.Thus far,there is no study on intellectual status in children with 22q11 DS in China. In this study,Wechsler Intelligence Scale for Children and Infants-Junior Middle School Students' Social-Life Abilities Scales were conducted to evulate their intelligence quotient(IQ) and social skills.The results showed that most patients with 22q11 DS in china have cognitive deficits ranging from mild to moderate intellectural disability, whose intellectural status are better than the children with William syndrome;their verbal IQs were lower than performance IQs which pattern is opposite to the ones in American patients,and such differences between these two populations might be result from different culture and special education system in these two country.When compared with chronological age matched controls,children with 22q11 DS in China developed poorer social skills,just as well as the mental age matched controls that were much younger.Moreover,different domains of social skills were unbalanced in children with 22q11DS.In order to improve the intellectual status in children with 22q11 DS in China,we need to strengen the special education,especially the speech therapy;targeted intervention shoud be based on patients' advantages and disadvantages,and social skills training shoud be develop step by step at the same time.