155 - Chromosome 4p Deletion Syndrome (Wolf-Hirschhorn Syndrome)

Abstract

First clinically described in 1961 by Hirschhorn and subsequently in 1965 by Wolf, the 4p deletion syndrome, or Wolf-Hirschhorn Syndrome (WHS), is the first example of a classic human chromosomal deletion syndrome. This rare condition, characterized by severe prenatal onset growth restriction, typical facial features, and severe seizures, is well described in the pediatric literature. Accounts of its prenatal presentation and diagnosis based on ultrasound findings and confirmatory genetic testing are more limited and consist of isolated case reports and small case series. Although more than 50% of deletions are visible by standard karyotyping, use of fluorescence in situ hybridization (FISH) and the now recommended array-based copy-number analysis or chromosomal microarray analysis (CMA) have improved the diagnosis of chromosome 4p deletions that cause WHS. Recently, noninvasive prenatal screening for microdeletion syndromes on cell-free fetal DNA (cffDNA) in maternal plasma has been developed and is being introduced in the clinic. This has widened the prenatal ascertainment for 4p deletion syndrome to a broader screen for potentially affected fetuses even in the absence of sonographic findings. Hence, practitioners should be familiar with the features of WHS syndrome that are detectable by prenatal imaging and those that are not prenatally observable, its prognosis, and the implications for perinatal management and counseling when a 4p deletion is detected prenatally.