Weaver Syndrome and EZH2-Related Overgrowth Syndromes

Comprehensive details on Weaver syndrome, one of the best recognized of the overgrowth syndromes, are presented in this chapter. The syndrome is characterized by overgrowth of prenatal onset, a distinctive craniofacial appearance, camptodactyly, widened metaphysis, accelerated bone age, and developmental delay. Like other overgrowth syndromes, Weaver syndrome is accompanied by an increased risk of malignancies, neuroblastoma, leukemia, and lymphoma in particular. The diagnosis relied on clinical evaluation alone until 2012 when the causative gene, EZH2, was discovered. The gene product joins with other related proteins to form a polycomb repressive complex that functions as an epigenetic signal that compacts chromatin and silences genes by histone modifications.