Focal Dermal Hypoplasia (Focal dermal hypoplasia) - Gen PORCN.

Focal Dermal Hypoplasia is a genetic disorder that primarily affects the skin, skeleton, eyes and face. About 90% of those affected are women. Males tend to have milder signs and symptoms than women. Although intelligence is not often affected, some people have intellectual disabilities.

Skin abnormalities may include dermal hypoplasia, fat nodules yellowish-pink color under the skin, aplasia cutis, telangiectasias, stripes slightly darker or lighter and skin papillomas. These skin changes can cause pain, itching, irritation, or result in skin infections. In addition, those affected may have small and ridged nails, as well as a hair in the small and fragile or absent scalp. Many individuals with focal dermal hypoplasia have abnormalities in hands and feet including oligodactyly, syndactyly, ectrodactilia and striated osteopathy. Moreover, eye abnormalities are common in people with focal dermal hypoplasia, including microphthalmia, Anophthalmia, problems with the tear ducts and incomplete development of the retina or optic nerve. This abnormal development of the retina and optic nerve can result in coloboma. Some of these ocular abnormalities not impair sight, while others may cause reduced vision or blindness.

Other signs associated with the disease include distinctive facial features, such as a pointed chin, small ears, nasal notch, facial asymmetry and cleft lip with or without cleft palate. Moreover, about half of individuals with focal dermal hypoplasia have dental abnormalities, especially enamel. Less often, they are present abnormalities of the kidneys and digestive system. The two kidneys may be fused, which predisposes individuals affected kidney infections, but however, do not usually cause significant health problems. The main gastrointestinal alteration that occurs in people with focal dermal hypoplasia omphalocele, which causes abdominal organs protrude through the navel. Signs and symptoms vary widely focal dermal hypoplasia, although nearly all affected individuals have skin abnormalities.

This process is due to mutations in the gene PORCN, located on the short arm of chromosome X (Xp11.23). This gene encodes a protein that belongs to a group of proteins called Porc. Although the precise function is unknown PORCN protein, the proteins in the Porc family are involved in the transfer process of palmitoleic acid to Wnt proteins. Wnt proteins involved in chemical signaling pathways in the body and play a critical role in development before birth. Porc members of the family are in the endoplasmic reticulum. Transfer palmitoleic acid Wnt proteins to facilitate the release of these proteins may regulate cell to the development of skin, bone and other structures.

They have identified at least 29 mutations in the gene responsible PORCN focal dermal hypoplasia. These genetic changes may alter the structure of the protein coding result an abnormally short version of the protein, or eliminate PORCN gene. All these mutations seem to lead to the absence of functional protein PORCN. Probably Wnt proteins can not be released without cell PORCN protein. When Wnt proteins are unable to leave the cell, they can not participate in chemical signaling pathways that are critical for normal development.

Focal Dermal Hypoplasia is inherited as a dominant X - linked pattern In women, a mutation in one of the two copies of the gene in each cell is sufficient to express the disease. The X chromosome containing the mutated gene PORCN can be active or inactive due to a process called inactivation of X. In early embryonic development in women, one of the two X chromosomes is inactivated permanently in somatic cells. X inactivation ensures that females, like males, have only one active copy of the X chromosome in each body cell. Generally X inactivation occurs randomly, so that each X chromosome is active in about half of the body 's cells. Sometimes X - inactivation is not random, and an X chromosome is present in more than half of the cells. It is believed that the distribution of active and inactive X chromosomes may play a role in determining the severity of the focal dermal hypoplasia in women. In males, a mutation in a single copy of the gene in each cell PORCN appears to be lethal in early development. A male may be born with focal dermal hypoplasia if a gene mutation has PORCN only in some cells (mosaicism). Affected males often have milder symptoms of the disease than women because more cells may have a functional copy of the gene PORCN. The focal dermal hypoplasia women can not transmit the disease to their children because it is lethal in early development, but can pass it on to their daughters. Most focal dermal hypoplasia cases in women are due to new mutations in the gene PORCN and occur in people with no history of disease in your family. When the focal dermal hypoplasia occurs in men, it is always due to a new mutation in this gene that is not inherited. Only about 5% of women with this disease inherit a mutation in the gene from one parent PORCN.

Tests in IVAMI: in IVAMI perform detection of mutations associated with focal dermal hypoplasia, by complete PCR amplification of exons PORCN 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).