Prenatal Screening and Diagnostic Considerations for 22q11.2 Microdeletions

Abstract

Diagnosis of a chromosome 22q11.2 microdeletion and its associated deletion syndrome (22q11.2DS) is optimally made early. We reviewed the available literature to provide contemporary guidance and recommendations related to the prenatal period. Indications for prenatal diagnostic testing include a parent or child with the 22q11.2 microdeletion or suggestive prenatal screening results. Definitive diagnosis by genetic testing of chorionic villi or amniocytes using a chromosomal microarray will detect clinically relevant microdeletions. Screening options include noninvasive prenatal screening (NIPS) and imaging. The potential benefits and limitations of each screening method should be clearly conveyed. NIPS, a genetic option available from 10 weeks gestational age, has a 70–83% detection rate and a 40–50% PPV for most associated 22q11.2 microdeletions. Prenatal imaging, usually by ultrasound, can detect several physical features associated with 22q11.2DS. Findings vary, related to detection methods, gestational age, and relative specificity. Conotruncal cardiac anomalies are more strongly associated than skeletal, urinary tract, or other congenital anomalies such as thymic hypoplasia or cavum septi pellucidi dilatation. Among others, intrauterine growth restriction and polyhydramnios are additional associated, prenatally detectable signs. Preconception genetic counselling should be offered to males and females with 22q11.2DS, as there is a 50% risk of transmission in each pregnancy. A previous history of a de novo 22q11.2 microdeletion conveys a low risk of recurrence. Prenatal genetic counselling includes an offer of screening or diagnostic testing and discussion of results. The goal is to facilitate optimal perinatal care.

Impact of high‐risk prenatal screening results for 22q11.2 deletion syndrome on obstetric and neonatal management: Secondary analysis from the SMART study

“…Early confirmation of 22q11.2DS is vital not just influencing parents' decisions regarding pregnancy continuation but also substantially improving the prospects for those affected. Recent literature highlights targeted interventions that can significantly enhance outcomes, 10–17 guided by newly updated health surveillance protocols catering to different age groups 20–28 . The review by Blagowidow et al (26) comprehensively outlines risks, benefits and limitations of approaches to pre and postnatal management of high‐risk infants.…”

“…The availability of targeted evaluations and interventions to improve outcomes for affected individuals should also be part of pre‐test counseling. If a patient declines prenatal genetic testing after a high‐risk screening result, prenatal sonographic surveillance and fetal echocardiography should be pursued 28 . Diagnostic testing, ideally using cord blood after delivery, 29 is important to optimize outcomes; an infant may have 22q11.2DS even if the physical examination is normal.…”

Chromosome 22q11.2 Deletion Syndrome: A Comprehensive Review of Molecular Genetics in the Context of Multidisciplinary Clinical Approach

“…The fetal fraction is screened for common trisomy and 22q11.2 deletion, as well as for other rare trisomies and microdeletions. Targeted technologies, such as single-nucleotide polymorphism (SNP)-based, digital analysis of selected regions (DANSR), and targeted capture enrichment assay (TCEA) technologies, as well as the genome-wide methodology massively parallel shotgun sequencing (MPSS), are advanced techniques used in cell-free DNA analysis [133][134][135][136][137].…”

Genetic Screening of Targeted Region on the Chromosome 22q11.2 in Patients with Microtia and Congenital Heart Defect

“…However, they share features including a heart defect, urogenital abnormalities, and velopharyngeal insufficiency. Among the various phenotypes, both ear malformations and heart malformations are represented in 22q11.2-related syndromes, respectively [ 15 , 16 ].…”