Fraternal twins with Phelan-McDermid syndrome not involving the SHANK3 gene: case report and literature review

BMC Medical Genomics

Ying Zhang¹  Juan Li¹  Meng Zhang²  Li-dong Zeng²  Ting Liu³  Ke-wang Xi³  Shan Li³ 

[1] Central Laboratory, The First Hospital of Lanzhou University, Lanzhou, China;GeneMind Biosciences Company Limited, Shenzhen, China;The First School of Clinical Medicine, Lanzhou University, Lanzhou, China;

关键词: Phelan-McDermid syndrome;    SHANK3;    22q13 interstitial deletion;    Neurodevelopmental disorders;   

DOI  :  10.1186/s12920-020-00802-0

来源: Springer

【 摘 要 】

BackgroundPhelan-McDermid syndrome (PMS, OMIM#606232), or 22q13 deletion syndrome, is a rare genetic disorder caused by deletion of the distal long arm of chromosome 22 with a variety of clinical features that display considerably heterogeneous degrees of severity. The SHANK3 gene is understood to be the critical gene for the neurological features of this syndrome.Case presentationWe describe one pair of boy-girl twins with a 22q13 deletion not involving the SHANK3 gene. Interestingly, the clinical and molecular findings of the two patients were identical, likely resulting from germline mosaicism in a parent. The boy-girl twins showed intellectual disability, speech absence, facial dysmorphism, cyanosis, large fleshy hands and feet, dysplastic fingernails and abnormal behaviors, and third-generation sequencing showed an identical de novo interstitial deletion of 6.0 Mb in the 22q13.31-q13.33 region.ConclusionsOur case suggests that prenatal diagnosis is essential for normal parents with affected children due to the theoretical possibility of parental germline mosaicism. Our results also indicated that other genes located in the 22q13 region may have a role in explaining symptoms in individuals with PMS. In particular, we propose that four candidate genes, CELSR1, ATXN10, FBLN1 and WNT7B, may also be involved in the etiology of the clinical features of PMS. However, more studies of smaller interstitial deletions with 22q13 are needed to corroborate our hypothesis and better define the genotype-phenotype correlation. Our findings contribute to a more comprehensive understanding of PMS.

【 授权许可】

CC BY