Craneoectodérmica dysplasia (Cranioectodermal dysplasia) - Genes WDR35, IFT122, WDR19, or IFT43.
The craneoectodérmica dysplasia is a disease that affects many parts of the body and characterized by bone abnormalities and abnormal development of ectodermal tissues, including skin, hair, nails and teeth.
Signs and symptoms of this disease vary among affected individuals, even among affected members of the same family. These signs and symptoms can include frontal bossing and dolichocephaly due to sagittal craniosynostosis set ears rotatable back telecanthus, upslanting or down palpebral fissures and metaphyseal dysplasia which causes short stature and limbs. Other features may include brachydactyly and narrow rib cage with short ribs, which can cause respiratory problems, especially in newborns affected. For its part, the abnormal development of tissues in people with ectodermal dysplasia craneoectodérmica can generate wispy hair, small or missing teeth, nails short and sagging skin.
This disease can affect additional organs and tissues in the body. Nephronophthisis occurs in many affected and may result in end - stage renal disease. Abnormalities of the liver, heart or eyes also occur in people with craneoectodérmica dysplasia.
The craneoectodérmica dysplasia is caused by mutations in one of at least four genes: the gene WDR35, located on the short arm of chromosome 2 (2p24.1), the IFT122 gene, located on the long arm of chromosome 3 (3q21), the WDR19 gene, located on the short arm of chromosome 4 (4p14) or IFT43 gene, located on the long arm of chromosome 14 (14q24.3). These genes encode proteins involved in the formation and maintenance of cilia. The cilia are important for the structure and function of many cell types, including cells of the kidneys, liver and brain. Photoreceptors in the retina also contain cilia, which are essential for normal vision. In addition, the cilia play a role in bone development, although the mechanism is not well understood. The protein encoded from each of these genes is a subunit of a protein complex called complex IFT A (IFT-A). This complex is in the cilia that project from the surface of cells. IFT-A complex is involved in the intraflagellar transport which moves molecules inside the cilia. This movement is essential for the assembly and maintenance of these structures. IFT-A complex materials transported from the tip to the base of the cilia. Moreover, the IFT-A complex is essential for proper regulation of the signaling pathway "Sonic Hedgehog", which is important for growth and differentiation, as well as the structural pattern of many parts of the body, especially during development embryonic. The exact role of the complex in this way is unclear.
They have identified at least eight mutations in the gene WDR35, two mutations in the gene WDR19, 6 IFT122 genetic mutations and one mutation in the gene IFT43 craneoectodérmica in people with dysplasia. Mutations in any of the four genes mentioned reduce the amount or function of the IFT-A subunits. Deficiency or abnormal function of a single complex component IFT-A prevents the function of the whole complex, disrupting the assembly and maintenance of the cilia. These mutations produce a lower cilia and anomalies in their shape and structure number. Although the mechanism is unclear, a loss of normal cilia prevents the proper development of bones, ectodermal tissues and other tissues and organs, leading to the characteristics of the craneoectodérmica dysplasia. About 40% of people with dysplasia craneoectodérmica have mutations in one of four known genes. The reason for the disease in people without mutations in one of these genes is unknown.
This disease 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.
Tests performed in IVAMI: in IVAMI perform detection of mutations associated with craneoectodérmica dysplasia, by complete PCR amplification of the exons of WDR35, IFT122, WDR19 and IFT43 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).