Introduction: The phenotypic variability in Beckwith-Wiedemann Syndrome reflects the genetic heterogeneity of the mechanisms which default leads to deregulation of genes located at 11p15.5. Genotype-phenotype correlation studies demonstrated an association between omphalocele and CDKN1C/p57 mutations or hypermethylation. Paternal UPD11 (pUPD11) has been described only in mosaic condition with both uniparental and biparental cell lines and no association with omphalocele has been pointed out.
Methods: Herein we present two cases in which a paternal segmental UPD11 was detected by molecular investigation of amniotic fluid cell cultures after the presence of apparently isolated omphalocele was revealed in the fetuses by ultrasound scan. Further studies were performed on additional autoptic feto-placental tissues to characterize the distribution of the uniparental cell line and unmask any biparental lineage in order to document more in detail the yet unreported association between omphalocele and pUPD11.
Results: Results on the UPD distribution profile showed that the abdominal organs have a predominant uniparental constitution. This condition could mimic the effect of CDKN1C/p57 inactivation causing the omphalocele.
Conclusions: New genotype-phenotype correlations emerge from the investigated cases suggesting to extend molecular analysis to all cases with fetal omphalocele in order to establish the incidence of pUPD11 not only in complete BWS but also in monosymptomatic/mild forms.
- Beckwith-Wiedemann Syndrome
- Prenatal Diagnosis