Incontinentia pigmenti; Bloch-Siemens-Sulzberger syndrome ...; (Incontinentia pigmenti, Bloch-Siemens-Sulzberger Syndrome) - Gen IKBKG

The Incontinentia pigmenti, also known as Syndrome Bloch-Siemens-Sulzberger syndrome or Bloch-Sulzberger, is a genetic process that affects many body organs, mainly the skin and occurs almost exclusively in women, not to survive most males during pregnancy, but only those having a very narrow genetic involvement or exhibiting mosaicism.

The process is characterized by the presence of skin abnormalities that evolve from birth to adolescence. Newborns skin lesions improve with time, and finally warty lesions may develop. Usually they occur in childhood gray or brown skin spots (hyperpigmentation), but these are disappearing and give rise to a Hypopigmented in the arms and legs linear lesions. In other affected, alopecia affecting the head or other body parts occurs; dental abnormalities, with small or few teeth; ocular abnormalities that can lead to loss of vision; ridged fingernails or flecked, etc. Most of those affected have normal intellectual development, but in some brain may be affected, and show mental retardation, seizures or other neurological problems.

Genetic alteration of this process occurs in the IKBKG gene (Inhibitor of Kappa-Light Polypeptide Gene Enhancer in B cells, Gamma Kinase), also called NEMO. This gene is located on the long arm of chromosome X (Xq28) and encodes a regulatory protein nuclear factor kappa beta (NFkB). For this, the IKBKG protein interacts with two enzymes: IKK-alpha and IKK-beta, which in turn activates the nuclear factor kappa-beta. This factor , when activated, moves to the cell nucleus and binds to DNA. In the cell nucleus regulates the expression of many genes, including genes that control the immune response and inflammatory reactions. It also protects the signals that induce apoptosis.

Have been described over 30 mutations in this gene but most affected (80%), the genetic alteration is loss of part of the gene (deletion). When these genetic alterations exist, a nonfunctional IKBKG protein is synthesized. At other times there is a loss of all IKBKG protein. When this protein IKBKG does not have its correct, or absent function, not the nuclear factor kappa-beta (NFKB) it is properly regulated, and the cells are much more sensitive to external signals, which leads to self - destruction (apoptosis).

The process has an autosomal X - linked, so that women, although they have two X chromosomes, gene disruption in one of the two chromosomes is sufficient to manifest the alteration. In males, who have only one X chromosome, in most cases death occurs early development, so very few are born affected by this process. Those who survive, and are born, have a moderate affectation or alteration occurs only in some cells (mosaicism). Some people inherit a IKBKG pigmenti Incontinentia 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 performed in IVAMI: in IVAMI perform detection of mutations associated with incontinentia pigmenti, by complete PCR amplification of exons IKBKG 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).