Carpenter syndrome ... (Carpenter syndrome) - Genes RAB23 or MEGF8.
Carpenter syndrome is a disorder characterized by craniosynostosis, abnormalities of the fingers and toes, and other developmental problems. Craniosynostosis prevents the skull grow normally, often causing acrocephaly. In people with severely affected, abnormal fusion of the skull bones produces a deformity called cloverleaf skull. Craniosynostosis can cause craniofacial asymmetry and intracranial pressure. In addition, it can affect the development of facial features resulting in a flat nasal bridge, slanted palpebral fissures, low - set ears and abnormally, underdeveloped upper and lower jaws and abnormal eye shape. Some affected individuals also have dental abnormalities including small primary teeth. Vision problems often occur. Abnormalities of the fingers and toes include cutaneous syndactyly, brachydactyly and polydactyly.
Other signs and symptoms of the disease may include mental retardation, obesity, umbilical hernia, hearing loss, heart defects, hip deformity, kyphoscoliosis, genu valgus, genital abnormalities in males as cryptorchidism and situs inversus certain organs such as dextrocardia. Signs and symptoms of this disease vary considerably, even within the same family. Life expectancy for people with Carpenter syndrome is reduced compared to the rest of the population.
Signs and symptoms of Carpenter syndrome are similar to other genetic alteration called cephalopolysyndactyly Greig syndrome. Some features overlap, including craniosynostosis, polydactyly and heart abnormalities, which can lead to some confusion in diagnosis. Because of this, they often require genetic testing for accurate diagnosis.
Carpenter syndrome is due to mutations in genes RAB23 and MEGF8.
The RAB23 gene, located on the short arm of chromosome 6 (6p11), encodes a protein involved in the process of movement of vesicles. This movement is important to transport molecules necessary for signaling during development. Through transport of certain proteins, the protein Rab23 regulates the hedgehog signaling pathway that is critical in proliferation and cell specialization and to the pattern of development in many parts of the organism during embryonic development. They have been linked over 12 RAB23 gene mutations with Carpenter syndrome. A mutation is observed frequently in affected individuals are of northern European descent replaces the amino acid leucine by an early stop signal at position 145 of the protein (Leu145Term or L145X). This mutation results in an abnormally short and unstable protein rapidly decomposes. Other genetic mutations reduce or eliminate the function of the protein Rab23. Although it is unclear how these mutations generate the characteristics of Carpenter syndrome it is likely to change in the transport of proteins involved in hedgehog signaling pathway contributes to the development of this disease.
The MEGF8 gene, located on the long arm of chromosome 19 (19q12), encoding a protein whose function is unclear. Based on its structure, the Megf8 protein may be involved in cellular processes such as cell adhesion and helps to proteins interact with each other. Furthermore, it is likely that Megf8 protein plays a role in the normal conformation of many parts of the organism during embryonic development. They have identified at least six mutations in the gene responsible MEGF8 Carpenter syndrome. These mutations reduce or eliminate the function of the protein Megf8. Although it is unclear how mutations in the gene lead to MEGF8 Carpenter syndrome is likely to interfere with the pattern of development in many parts of the body, contributing to the characteristics of this disease.
This disease is inherited in an autosomal recessive pattern, that is, 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.
Tests in IVAMI: in IVAMI perform detection of mutations associated with Carpenter syndrome, by complete PCR amplification of the exons of RAB23 and MEGF8 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).