Recurrent Wiedemann-Beckwith syndrome with inversion of chromosome (11)(p11.2p15.5)

Area of Science:

• Genetics
• Developmental Biology
• Medical Genetics

Background:

• Wiedemann-Beckwith syndrome (WBS) is a complex overgrowth disorder with variable clinical features.
• Genetic factors, particularly those on chromosome 11p15.5, are implicated in WBS pathogenesis.
• Genomic imprinting plays a crucial role in the regulation of genes in the 11p15.5 region.

Purpose of the Study:

• To investigate the genetic basis of WBS in a family with a suspected chromosomal abnormality.
• To determine the inheritance pattern of a paracentric inversion in chromosome 11.
• To explore the potential link between the identified inversion and WBS in the affected infant.

Main Methods:

• Karyotyping was performed on affected and unaffected family members.
• Cytogenetic analysis identified a paracentric inversion, inv(11)(p11.2 15.5), in the short arm of chromosome 11.
• Ultrasound examination was used to assess fetal development.

Main Results:

• The affected infant and her phenotypically normal mother shared the same paracentric inversion, inv(11)(p11.2 15.5).
• A fetus, sibling to the affected baby, also carried the inversion and presented with exomphalos on ultrasound.
• The maternal grandmother was clinically and cytogenetically normal, indicating the inversion arose in a more recent generation.

Conclusions:

• The family's pattern of affection supports the hypothesis that WBS can result from the disruption of a maternally imprinted gene at 11p15.5.
• The identified paracentric inversion, inv(11)(p11.2 15.5), is likely responsible for disrupting this critical gene in the affected individuals.
• This case highlights the role of chromosomal rearrangements in imprinting disorders like WBS.