Weaver syndrome is an autosomal dominant rare overgrowth syndrome distinguished by accelerated osseous maturation correlated with craniofacial, limb, neurological, skeletal and further abnormalities. Craniofacial symptoms include macrocephaly, broad forehead, hypertelorism, telecanthus, large and low-set ears, long and prominent philtrum, and relative micrognathia. Limb abnormalities consist of prominent finger pads, thin and deeply-set nails, camptodactyly, wide distal long bones, foot deformities, and broad thumbs. Further associated anomalies include psychomotor retardation, hoarse and low-pitched voice, hypertonia, umbilical and inguinal hernia, and excess loose skin. To this point, 30 cases have been reported, most of them being sporadic, however, two families were portrayed as having an autosomal dominant transmission. Prognosis varies with every case as some patients retain a normal life span and with an ordinary adult height. Curative treatments are not available, though every case must be adapted to a multidisciplinary (e.g., neurological, pediatric, orthopedic, genetic counseling, and psychomotor care) management. Though both sexes are affected with Weaver syndrome, the sex ratio was established as 2M:1F.

Amongst Weaver syndrome patients tested, some revealed intragenic mutations in the NSD1 gene (nuclear receptor binding SET domain protein 1), which is also associated with Sotos syndrome. The majority of identified NSD1 functional domains are located in exons 11-23 and the entire recognized mutations were clustered in these mutations. The mutations that are associated with Weaver syndrome are positioned in a minor specific fraction of the gene in exons 5, 16, 19, 22, and 23. The detection of NSD1 mutation in Weaver and Sotos syndrome patients reveals that both disorders are allelic, nevertheless, the possibility of a second separate Weaver syndrome gene exists. The precise pathophysiology and the etiology of the residual cases remain vague.

NSD1 gene provides directions for creating a protein with unknown function. This protein is active in numerous organs and tissues, comprising the brain, the kidney, skeletal muscle, spleen, thymus, and lungs. Investigators presumed that the NSD1 protein controls the activity of specific genes engaged in normal growth and development, and have the ability of turning genes on or off as required.