Prenatal testing for uniparental disomy: indications and clinical relevance

Abstract

This review aims to provide a rational and ethical basis for prenatal testing for uniparental disomy (UPD) in cases with abnormal ultrasound findings or numeric and/or structural chromosomal aberrations in chorionic villous or amniotic fluid samples. The clinical phenotypes of the genomic imprinting-associated paternal UPD 6 (transient neonatal diabetes mellitus), maternal UPD 7 (Silver-Russell syndrome), paternal UPD 11p (Beckwith-Wiedemann syndrome), maternal UPD 14 (precocious puberty, short stature and highly variable developmental delay), paternal UPD 14 (polyhydramnios and a bell-shaped thorax), maternal UPD 15 (Prader-Willi syndrome), paternal UPD 15 (Angelman syndrome), maternal UPD 16 and UPD 20, as well as the diagnostic options, are summarized. In addition, the clinical impact of UPD testing and its relevance in various prenatal diagnostic situations are discussed. As a general rule, prenatal UPD testing, following genetic counseling, is justified if paternal UPD 14, maternal UPD 15 or paternal UPD 15 are suspected. In contrast, considering the mild phenotypes of paternal UPD 6 and maternal UPD 7, prenatal UPD testing is questionable. Because of the highly variable phenotype for paternal UPD 11p, maternal UPD 14 and maternal UPD 16, prenatal testing should be discussed critically on an individual basis. For all other chromosomes, prenatal UPD testing is purely academic and should therefore not be performed on a routine basis, particularly because a positive result might confuse the parents more than it actually helps them.