Hemihypertrophy of one leg and congenital retroperitoneal tumor: Beckwith-Wiedemann syndrome

Abstract

Beckwith-Wiedemann syndrome (BWS) belongs to the so-called imprinting disorders and has an incidence of 1:15’000 – 26’000. It is characterized as an overgrowth syndrome with variable expression of symptoms such as exomphalos, macroglossia, neonatal hypoglycemia, earlobe creases, hemihypertrophy, perinatal overgrowth and an increased risk of embryonic tumors. Genomic imprinting leads to an altered expression of gene parts dependent on parental heredity due to DNA-methylation. The affected (imprinted) regions in BWS are typically located on chromosome 11p15.5. The respective genes have regulatory function for cellular growth with the epigenetic changes leading to either decreased inhibition or increased expression of growth promoting genes. In BWS, about 50 % of the infants show a loss of methylation in the Imprinting Control Region (ICR)-2, normally expressed by the maternal chromosome only, leading to a reduced expression of a growth inhibitor gene (CDKN1C). In 5 –10 % of BWS, gain of methylation in the telomeric ICR-1 results in an increased expression of the insulin-growth-factor-2 gene (usually only expressed by the paternal allele) and a reduced expression of the oncosuppressor gene H19 which is usually expressed by the maternal allele. 20 –25 % of patients with BWS show paternal uniparental disomy (UPD) of chromosome 11 (patUPD11) resulting in an altered methylation at both regions ICR-1 and ICR-2 with only paternal alleles. In 10 % of all BWS cases, the reason remains unclear with unknown molecular defects