Kleefstra syndrome ... (Kleefstra syndrome) - Genes EHMT1 and chromosome 9

Kleefstra syndrome is a genetic condition characterized by developmental delay and intellectual disability, severe delay in speaking, hypotonia and a distinctive facial appearance.

The facial features of individuals with Kleefstra syndrome usually include microcephaly and brachycephaly, synophrys, hypertelorism, midface hypoplasia, anteverted nares, undershot, everted lips and macroglossia. Affected individuals may have a high birth weight and childhood obesity. Other signs and symptoms may include additional structural brain abnormalities, congenital heart defects, genitourinary abnormalities, seizures and a tendency to develop serious respiratory infections. During childhood can manifest features of autism or related to development affecting communication and social interaction disorders. In adolescence, they may develop apathy or catatonia.

Kleefstra syndrome is due to a loss of EHMT1 gene or mutations that inactivate its function. The EHMT1 (euchromatic histone-lysine N-methyltransferase 1) gene, located on the long arm of chromosome 9 (9q34.3), encoding the histone methyltransferase enzyme euchromatic 1. methyltransferases histones are enzymes that modify histones. Histones are structural proteins that bind to DNA and chromosomes shape. By adding a methyl group to histones, histone methyltransferases can suppress the activity of certain genes, which is essential for the normal development and function.

Most people with Kleefstra syndrome have a deletion of approximately one million base pairs in one copy of chromosome 9 in each cell. The deletion occurs near the end of the long arm, q34.3, a region containing the gene EHMT1. Some affected individuals have shorter or longer deletions in the same region. It is believed that loss of one copy of the gene in each cell EHMT1 is responsible for the characteristic features of the Kleefstra syndrome in people with 9q34.3 deletion. However, the loss of other genes in the same region can lead to additional health problems in some affected individuals.

About 25% of individuals with Kleefstra syndrome have a deletion of genetic material from chromosome 9; Instead, these individuals have mutations in the gene EHMT1. Some of these mutations change amino acids in the histone methyltransferase euchromatic 1, whereas other genetic changes creates a premature stop signal in encoding the enzyme or alter the way in which the enzyme is encoded. These changes generally result in the synthesis of an enzyme which is unstable and decomposes rapidly, or can not function properly. Deficiency or absence of functional euchromatic histone methyltransferase 1 affects the proper control of the activity of certain genes in many organs and tissues, leading to developmental anomalies and the operation characteristics of Kleefstra syndrome.

Heritage of Kleefstra syndrome is considered to be autosomal dominant because a deletion in one copy of chromosome 9 in each cell or a mutation in a gene copy EHMT1 is sufficient to express the process. However, most cases of Kleefstra syndrome are not inherited. The genetic change occurs more frequently as a random event during the formation of reproductive cells or early fetal development. Affected individuals often have no history of the disease in your family, even though they can transmit the disease to their children. Rarely, affected individuals inherit one chromosome 9 with an removed from an affected parent segment. In these cases, the parent carries a balanced translocation in which no genetic material is gained or lost. Balanced translocations usually do not cause any health problems; however, they may become unbalanced as they are transmitted to the next generation. Children who inherit an unbalanced translocation may have a chromosomal rearrangement extra or missing genetic material. Individuals with Kleefstra syndrome inherit an unbalanced translocation have an absence of genetic material from the long arm of chromosome 9. A few individuals with Kleefstra syndrome have inherited a chromosome 9q34.3 deletion of an unaffected parent, a mosaic for deletion, which means that a person has the deletion in some cells but not others.

Tests in IVAMI: in IVAMI perform detection of mutations associated with syndrome Kleefstra, by complete PCR amplification of exons EHMT1 gene, 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).