Genetic testing for unexplained perinatal disorders

Abstract

Purpose of review: Perinatal disorders include stillbirth, congenital structural anomalies, and critical illnesses in neonates. The cause of these is often unknown despite a thorough clinical workup. Genetic diseases cause a significant portion of perinatal disorders. The purpose of this review is to describe recent advances in genetic testing of perinatal disorders of unknown cause and to provide a potential diagnostic strategy.

Recent findings: Exome and genome sequencing (ES and GS) have demonstrated that significant portions of perinatal disorders are caused by genetic disease. However, estimates of the exact proportion have varied widely across fetal and neonatal cohorts and most of the genetic diagnoses found in recent studies have been unique to individual cases. Having a specific genetic diagnosis provides significant clinical utility, including improved prognostication of the outcome, tailored therapy, directed testing for associated syndromic manifestations, referral to appropriate subspecialists, family planning, and redirection of care.

Summary: Perinatal disorders of unknown cause, with nonspecific presentations, are often caused by genetic diseases best diagnosed by ES or GS. Prompt diagnosis facilitates improved clinical care. Improvements in noninvasive sampling, variant interpretation, and population-level research will further enhance the clinical utility of genetic testing.

Video abstract: http://links.lww.com/MOP/A61.

Figure 1.

Spectrum of genetic diagnoses from genetic investigations of perinatal disorders. Individual cases were abstracted from recent studies of fetal and neonatal disorders. These cases were assigned to broad categories of perinatal disorders, represented by the inner disc. The specific genetic diagnoses from each case are represented in the outer ring, with the number of cases shown in parentheses.