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AD = autosomal dominant; ESRD = end-stage renal disease; GU = genitourinary; ID = intellectual disability; MOI = mode of inheritance

Halliday et al [2018], Diets et al [2019], Mahamdallie et al [2019], Hol et al [2021a]

Germline WT1 pathogenic variants have a greater effect on sex determination and genital tract development in males; 46,XX females with a germline WT1 pathogenic variant are less likely to exhibit genitourinary anomalies.

In the absence of genitourinary anomalies, renal mesangial sclerosis, nephrogenic rests, or bilateral tumors, the likelihood that a child with Wilms tumor has a germline WT1 pathogenic variant is 0%-5%. A small number of families with isolated Wilms tumor have heterozygous germline WT1 pathogenic variants.

Isolated Wilms tumor has been associated with constitutional alterations of chromosome 11p15 most commonly hypermethylation at IC1 and paternal uniparental disomy of 11p15. Loss of methylation at IC2 and genomic abnormalities of 11p15 may be associated with Wilms tumor but reports are rare and the evidence is still emerging.

Molecular alterations at 11p15 including loss of methylation at IC2, gain of methylation at IC1, and 11p15 paternal uniparental disomy have been reported in individuals who have apparently isolated hemihyperplasia (see Beckwith-Wiedemann Syndrome, Allelic Disorders).

85% of individuals with BWS have no family history of BWS; approximately 15% have a family history consistent with parent-of-origin autosomal dominant transmission.