Abstract
Beckwith-Wiedemann syndrome (BWS; MIM# 130650) is a well-characterized pediatric overgrowth disorder. In approximately 5% of the cases, it is caused by pathogenic variants in the CDKN1C (cyclin-dependent kinase inhibitor 1C). CDKN1C gene encodes for a protein p57 (KIP2) that acts as an inhibitor of cyclin-dependent kinases (CDK) that are expressed in the G and S-phase of the cell cycle, thus regulating cellular proliferation. Variants in CDKN1C gene lead to loss of inhibitory function of CDK and thus impair the inhibition of growth, resulting in BWS phenotype.
We describe here a 2.5-year-old boy with a maternally inherited variant c.182G > T, p.Trp61Cys in the CDKN1C gene causing BWS. The natural history of the disorder is described along with the gradual change in the facial features. An insight into the genotype–phenotype correlation and disorders to be considered in the differential diagnosis is provided. We describe a common overgrowth syndrome with its rare genetic mechanism and highlight the salient features that help in making a diagnosis and managing patients.
Keywords
BWS - CDKN1C - MS-MLPA - overgrowth syndrome - genotype–phenotype correlation
