Prader-Willi and Angelman syndromes — branching viva

Opening framework

My framework has four layers. First, the shared mechanism — both are reciprocal disorders of genomic imprinting at chromosome 15q11-q13, where parent-of-origin-specific methylation controls which parental allele is expressed. Second, the reciprocal error — loss of paternally expressed genes (SNRPN, MAGEL2, NDN, SNORD116) produces PWS, and loss of maternal UBE3A expression in the brain produces AS. Third, the investigation — methylation analysis (MS-PCR or MS-MLPA) at the SNRPN locus is the first-tier test for both, because a single assay detects the imprinting abnormality and distinguishes PWS from AS. Fourth, the family — subtype determination (deletion, UPD, imprinting defect, UBE3A mutation) sets recurrence risk, and counselling must be imprinting-aware. ^{[3] [4]}