Hay-Wells syndrome ... Syndrome (ACS) (Hay-Wells syndrome) - Gen TP63
Syndrome Hay-Wells, also known as AEC syndrome (Ankyloblepharon filiform adnatum, Ectodermal effects, Cleft lip / palate - A nquilobléfaron filiform to epithelial -insulated birth between eyelids, ectodermal dysplasia, cleft lip / palate) is a form of ectodermal dysplasia, congenital abnormalities characterized by skin erosions on the scalp, recurrent infections and abnormal teeth, nails and mucosa. Additional features of the AEC syndrome may include limb abnormalities, syndactyly in hands and feet, camptodactilia or ectrodactilia. Some affected individuals have distinctive facial features such as small jaws that can not be opened fully and philtrum. Other signs and symptoms may include hypospadias in affected males, digestive problems, lack of tear duct openings and chronic sinusitis or ear infections.
A syndrome known as Rapp-Hodgkin syndrome has signs and symptoms overlap considerably with AEC syndrome. These two syndromes were classified as separate until it was discovered that both were due to mutations in the same part of the same gene processes. Because it is considered that the syndrome Rapp-Hodgkin syndrome AEC are part of the same disease spectrum. Likewise, the Hay-Wells syndrome shows common features with EEC syndrome (ectrodactyly, ectodermal dysplasia, cleft lip / palate -electrodactilia, ectodermal dysplasia and cleft lip / palate hendidos-) and ADULT syndrome, although the latter to a lesser as with the first.
They are generated by mutations in the TP63 gene, located on the long arm of chromosome 3 (3q28). This gene encodes a protein called transcription factor protein p63 tumor (p63). The action of p63 helps regulate many cellular activities, including growth and cell proliferation, the maintenance of cells, cell differentiation, cell adhesion and apoptosis. This protein plays a critical role in early development. It is especially important for the normal development of ectodermal, such as skin, hair, teeth and nails structures. Also, this protein plays an essential role in the development of limbs, facial features, urinary system, and other organs and tissues. In addition to their roles in development, the p63 protein appears to be required for maintenance of various cells and tissues throughout life.
They have identified at least 40 mutations in the TP63 gene in people with this syndrome. Most mutations associated with the syndrome are located in the domain alpha-sterile motif (SAM) and transactivation domain inhibitory (TI). These genetic changes disrupt the interaction with other proteins, altering transcriptional repression of other related or give rise to a splicing (cutting and sealing) abnormal keratinocyte growth factor genes. However, it is unclear how these changes result in an abnormal ectodermal development and specific features of the syndrome.
Syndrome Hay-Wells is inherited in an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient to express the process. In some cases, an affected person inherits the mutation from an affected parent. Other cases are due to new mutations in the gene and occur in people with no history of disease in your family.
Tests in IVAMI: in IVAMI perform detection of mutations associated with Hay-Wells syndrome by complete PCR amplification of the exons of TP63 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) if postnatal diagnosis. For prenatal diagnosis, amniotic fluid or chorionic villi.