Weaver syndrome ... (Weaver syndrome) - Gen EZH2

Weaver syndrome is a disorder characterized by skeletal abnormalities and developmental delay. It is considered an overgrowth syndrome because the bones of affected individuals grow and develop faster than normal, both before and after birth. In addition to advanced bone age, affected persons may have other skeletal abnormalities, including foot deformities, permanently bent joints as wide camptodactilia and thumbs. Referring to the characteristic features of the head and face, they may include macrocephaly, occiput front wide, Hypertelorism, large and low set ears, philtrum, a dimple in the chin and micrognatia.

People with Weaver syndrome have a hoarse sound weak and delayed development of motor skills in early childhood. Usually, these individuals have mild intellectual disability and lack of coordination and balance. Other signs and symptoms may include kyphoscoliosis, abnormal gyri, hypotonic or hypertonic, sagging skin and umbilical hernia or inguinal hernia. People with Weaver syndrome have an increased risk of developing cancer, but the small number of individuals affected hinders accurate risk assessment.

Overall, Weaver syndrome is due to mutations in the gene EZH2 (enhancer of zeste 2 polycomb repressive complex subunit 2), located on the long arm of chromosome 7 (7q35-q36), encoding the histone methyltransferase enzyme. This enzyme modified histone proteins called, which bind DNA and chromosomes shape. By adding a methyl group to histones (methylation), histones methyltransferases can suppress the activity of certain genes, an essential process in normal development. Specifically, the enzyme encoded from EZH2 gene is part of a group of proteins called the repressive complex 2 polycomb. By inactivating genes, this complex is involved in cell fate determination.

They have identified more than 30 mutations of EZH2 gene in people with Weaver syndrome. Most of these mutations consist of amino acid changes in the enzyme EZH2. Other mutations insert or remove small amounts of genetic material EZH2 gene, leading to synthesis of an altered enzyme EZH2. Although it is unclear how these mutations EZH2 gene result characteristics Weaver syndrome, likely to disrupt the methylation process and affect the regulation of certain genes in many organs and tissues, resulting in Weaver syndrome abnormalities.

Weaver syndrome is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient to express the disease. Almost all cases are due to new mutations in the gene and occur in people with no history of disease in your family. In a small number of cases, an affected person inherits the mutation from an affected parent.

Tests in IVAMI: in IVAMI perform detection of mutations associated with Weaver syndrome by complete PCR amplification of the exons of the gene EZH2, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).