Weaver syndrome

Weaver syndrome (also known as Weaver-Smith syndrome) is a rare genetic overgrowth disorder characterized by accelerated skeletal maturation (advanced bone age), tall stature, and a distinctive facial appearance. The condition is primarily caused by pathogenic variants in the EZH2 gene, which encodes a histone methyltransferase involved in epigenetic regulation of gene expression. Most cases arise from de novo (new) mutations, though familial transmission has been documented. The syndrome affects multiple body systems. Skeletal features include accelerated osseous maturation, broad thumbs, camptodactyly (permanently bent fingers), clinodactyly, and widened distal long bones. Craniofacial characteristics typically include a broad forehead, hypertelorism (widely spaced eyes), a long philtrum, large ears, and relative macrocephaly. Affected individuals frequently experience intellectual disability of variable severity, ranging from mild learning difficulties to moderate cognitive impairment. Hypotonia (low muscle tone) is common in infancy and may contribute to delayed motor milestones. Some individuals may also have loose, redundant skin, a hoarse or low-pitched cry in infancy, and umbilical hernia. There is no specific cure or targeted therapy for Weaver syndrome. Management is supportive and multidisciplinary, involving pediatric endocrinology, orthopedics, developmental pediatrics, and speech therapy as needed. Early intervention programs for developmental delays are recommended. Notably, individuals with EZH2 mutations may have an increased predisposition to certain malignancies, including neuroblastoma and hematologic cancers, warranting appropriate surveillance. Regular monitoring of growth, development, and skeletal maturation is an important component of ongoing care.

Common questions about Weaver syndrome