Also known as Weaver-Smith Syndrome. First described in 1974 by Dr. David Weaver.
A syndrome of large birth size, accelerated growth and skeletal maturation, associated with limb, craniofacial, neurological, and other abnormalities. Craniofacial anomalies consist of a broad forehead, flat occiput, large ears, hypertelorism, long philtrum, and relative micrognathia. Limb abnormalities include prominent finger pads, camptodactyly, broad thumbs, thin and deep-set nails, clinodactyly, limited elbow and knee extension, wide distal long bones, and foot deformities (clubfoot, pes calcaneovalgus, and metatarsus adductus). Hypertonia, hypotonia, psychomotor retardation, and hoarse, low-pitched voice, excess loose skin, umbilical and inguinal hernia, and inverted nipples are associated. The aetiology is unknown.
(Adapted from: http://www.whonamedit.com/synd.cfm/1360.html)
What genes are related to Weaver Syndrome?
Weaver syndrome is usually caused by mutations in the EZH2 gene; rare cases associated with mutations in the NSD1 gene have also been reported. The EZH2 gene provides instructions for making a type of enzyme called a histone methyltransferase. Histone methyltransferases modify proteins called histones, which are structural proteins that attach (bind) to DNA and give chromosomes their shape. By adding a molecule called a methyl group to histones (methylation), histone methyltransferases can turn off (suppress) the activity (expression) of certain genes, which is an essential process in normal development. Specifically, the EZH2 enzyme forms part of a protein group called the polycomb repressive complex-2. By turning off particular genes, this complex is involved in the process that determines the type of cell an immature cell will ultimately become (cell fate determination). Mutations in the EZH2 enzyme may disrupt methylation and impair regulation of certain genes in many of the body’s organs and tissues, resulting in the abnormalities characteristic of Weaver syndrome.
The NSD1 gene provides instructions for making a protein whose full range of functions is unknown. Researchers believe that this protein controls the expression of certain genes involved in normal growth and development, and can turn genes on or off as needed. The mutations apparently impair the normal regulation of gene expression. A few individuals with NSD1 gene mutations have been diagnosed with Weaver syndrome. However, some researchers believe that these cases should be classified as unusual presentations of a similar disorder called Sotos syndrome, which is caused by NSD1 gene mutations.