Reproductive Health Issues for Adults with a Common Genomic Disorder: 22q11.2 Deletion Syndrome
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22q11.2 deletion syndrome (22q11.2DS) is the most common microdeletion syndrome in humans. Survival to reproductive age and beyond is now the norm. Several manifestations of this syndrome, such as congenital cardiac disease and neuropsychiatric disorders, may increase risk for adverse pregnancy outcomes in the general population. However, there are limited data on reproductive health in 22q11.2DS. We performed a retrospective chart review for 158 adults with 22q11.2DS (75 male, 83 female; mean age 34.3 years) and extracted key variables relevant to pregnancy and reproductive health. We present four illustrative cases as brief vignettes. There were 25 adults (21 > age 35 years; 21 female) with a history of one or more pregnancies. Outcomes for women with 22q11.2DS, compared with expectations for the general population, showed a significantly elevated prevalence of small for gestational age liveborn offspring (p < 0.001), associated mainly with infants with 22q11.2DS. Stillbirths also showed elevated prevalence (p < 0.05). Not all observed adverse events appeared to be attributable to transmission of the 22q11.2 deletion. Recurring issues relevant to reproductive health in 22q11.2DS included the potential impact of maternal morbidities, inadequate social support, unsafe sexual practices, and delayed diagnosis of 22q11.2DS and/or lack of genetic counseling. These preliminary results emphasize the importance of early diagnosis and long term follow-up that could help facilitate genetic counseling for men and women with 22q11.2DS. We propose initial recommendations for pre-conception management, educational strategies, prenatal planning, and preparation for possible high-risk pregnancy and/or delivery.
KeywordsDiGeorge syndrome Contraception Velocardiofacial syndrome Prenatal testing Pregnancy complications Genomic disorder
The authors thank the adults with 22q11.2DS and their families for their generous contributions to this and related research studies. The authors express gratitude to the students, research assistants, and staff affiliated with the Clinical Genetics Research Program, Clinical Genetics Service, and Toronto Congenital Cardiac Centre for Adults (TCCCA). Special thanks go to Fiona Fu, Lisa Palmer, and Monica Torsan. This work was supported by Canadian Institutes of Health Research (CIHR) grants (MOP-97800 and MOP-89066), MD/PhD studentships from CIHR and the McLaughlin Centre (to Gregory Costain), and an award from the Mach-Gaensslen Foundation administered through the Comprehensive Research Experience for Medical Students (CREMS) summer research program (to Chrystal Chan). Anne S. Bassett holds the Canada Research Chair in Schizophrenia Genetics and Genomic Disorders, and the Dalglish Chair in 22q11.2 Deletion Syndrome.
Conflict of Interest Statements
Chrystal Chan, Gregory Costain, Lucas Ogura, Candice K. Silversides, Eva W.C. Chow, and Anne S. Bassett declare that they have no conflict of interest.
Human Studies and Informed Consent
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study.
No animal studies were carried out by the authors for this article.
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