Acrocallosal syndrome ... (Acrocallosal syndrome) - Genes KIF7 and GLI3
The acrocallosal syndrome (ACLS), also known as Schinzel syndrome 1, is a rare disorder characterized by agenesis of corpus callosum, Polydactyly and distinctive facial features. Signs and symptoms of the syndrome are present at birth, and their severity varies widely among affected individuals.
Agenesis of the corpus callosum occurs when the tissue that connects the left and right halves of the brain does not form properly during the early stages of development before birth. Other brain abnormalities, including growth of large cysts in brain tissue, have also been reported in people with acrocallosal syndrome. These changes in brain structure are responsible for a late development and intellectual disability. Some affected people also suffer from seizures.
As for polydactyly, extra digits may be on the same side of the hand or the foot, polydactyly or preaxial postaxial polialactilia still prevalent. In addition, some affected individuals have sindactilia. The characteristic facial features may include macrocephaly, hypertelorism and a high and prominent forehead.
This process is usually due to mutations in the gene KIF7 (kinesin family member 7), located on the long arm of chromosome 15 (15q26.1), which encodes a protein that is associated with the primary cilia. These microscopic projections are involved in signaling pathways that transmit information to cells. Studies suggest that the protein KIF7 helps maintain proper length and stability of the cilia. Through their association with the primary cilia, the KIF7 protein helps regulate a signaling pathway known as Sonic Hedgehog. This pathway is essential for early development. Plays roles in cell growth, cell specialization and the formation of many parts of the body, including the brain and extremities.
They have identified at least 20 KIF7 gene mutations in people with acrocallosal syndrome. Most of these mutations result in the synthesis of an abnormally short, nonfunctional version KIF7 protein or inhibit the synthesis of this protein from the gene. Although little is known about the effects of these mutations it is likely to disrupt Sonic Hedgehog signaling in early development. However, it is unclear how these changes affect the developing brain, limbs and other body parts in those affected.
In addition to mutations in the gene KIF7, mutations in the gene GLI3 (GLI family zinc finger 3), may also lead to the development of some features of this syndrome. However, the signs and symptoms overlap significantly with a similar condition called cephalopolysyndactyly syndrome Greig (which is also due to mutations of the GLI3 gene), so the acrocallosal syndrome that develops as a result of mutations GLI3 gene it is sometimes considered a severe form of cefalopolisodactilia Greig syndrome.
GLI3 (GLI family zinc finger 3) gene, located on the short arm of chromosome 7 (7p14.1), encodes the synthesis of GLI proteins that control gene expression, and therefore are involved in growth, cell specialization structure brain and extremities. GLI proteins family act in the same molecular pathway that Sonic Hedgehog. By interacting with certain genes at specific times during development, the GLI3 protein plays a role in the normal formation of many organs and tissues before birth.
They have been described at least two mutations in the GLI3 gene in people with features acrocallosal syndrome. The identified mutations consist of amino acid changes in a particular region of the GLI3 protein which inhibits the function of the protein. Defective protein likely alters the expression of certain genes in early development. GLI3 the role of protein in the pattern of brain and extremities may help explain why mutations lead to brain anomalies, polydactyly and other characteristics of acrocallosal syndrome.
When acrocallosal syndrome is due to mutations KIF7 gene is inherited in an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease. Meanwhile, when the syndrome is due to mutations GLI3 gene is considered to have an autosomal dominant hereditary type, it implies that a copy of the altered gene in each cell is sufficient to express the disease. This process is usually due to new mutations in the gene that occur during the formation of reproductive cells or early embryonic development. These cases occur in people with no history of disease in your family.
Tests in IVAMI: in IVAMI perform detection of mutations associated with acrocallosal syndrome (ACLS), by complete PCR amplification of the exons of KIF7 and GLI3 genes, respectively, 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).