11p15

11p15 refers to a segment on the short arm of chromosome 11, most notably the imprinted domain at 11p15.5. This region contains a cluster of imprinted genes and two imprinting control regions, IC1 and IC2, which regulate parent-of-origin–specific gene expression. Key genes in this area include IGF2 and H19, whose expression is controlled by IC1, and a gene cluster involving KCNQ1, KCNQ1OT1 (an antisense transcript), and CDKN1C, whose activity is regulated by IC2. The imprinting status of 11p15 is determined by DNA methylation patterns, which can be altered in disease.

Alterations at 11p15 are central to several imprinting disorders, most prominently Beckwith-Wiedemann syndrome (BWS) and Silver-Russell syndrome (SRS). In BWS, epigenetic changes such as paternal uniparental disomy of 11p15, or abnormal methylation that increases IGF2 expression (gain of methylation at IC1) or decreases CDKN1C expression (loss of methylation at IC2) lead to overgrowth and increased tumor risk. In SRS, hypomethylation of IC1 or related defects reduce IGF2 expression, contributing to growth retardation and distinct clinical features. The 11p15 region is also linked to an elevated risk of embryonal tumors, notably Wilms tumor and hepatoblastoma, particularly in BWS.

Diagnosis relies on targeted epigenetic testing of 11p15, including methylation analysis and copy-number assessment, such as methylation-specific assays and MLPA, complemented by SNP-based methods to detect uniparental disomy. Management typically includes growth and metabolic monitoring and, where indicated, cancer surveillance tailored to the underlying imprinting disturbance.

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