Laringo-onycho-cutaneous syndrome ... (Laryngo-onycho-cutaneous syndrome) - Gen LAMA3.
The laryngo- onycho cutaneous syndrome (LOC) is a disorder characterized by abnormalities of the larynx, finger and toe nails, and skin. Many of the signs and symptoms of this disease are related to the abnormal growth of granulation tissue in different parts of the body. This granulation tissue, typically occurs during wound healing and are generally replaced by skin cells as the healing process progresses. However, in people affected, this tissue grows even when there is no serious injury.
One of the first symptoms in newborns with LOC syndrome is driven by a hoarse cry ulcers or tissue overgrowth granulation larynx. Excessive granulation tissue may also block the airway, causing potentially fatal respiratory problems. As a result, many individuals affected do not survive beyond infancy. In LOC syndrome, granulation tissue grows also in the eyes, specifically in the conjunctiva. People usually have impaired or complete loss of vision due to excessive tissue growth. Another common feature of the LOC syndrome are cutaneous erosions that heal slowly and can become infected. People with LOC syndrome may also have abnormally small misshapen nails and teeth. In addition, the tooth enamel is thin, contributing to frequent caries.
LOC syndrome is considered a subtype of another skin condition called epidermolysis bullosa binding. While people with epidermolysis bullosa binding may have some of the characteristics of LOC syndrome, they tend not to have excessive growth of granulation tissue in the conjunctiva.
This process is due to mutations in the gene LAMA3, located on the long arm of chromosome 18 (18q11.2). This gene encodes an alpha subunit of laminin protein 332, formerly known as laminin 5. This protein consists of the alpha subunits, beta, and gamma. Beta and gamma subunits are encoded from other genes. Three versions of the alpha subunit (alpha-3a, alpha-3b1 and 3b2 alpha) are coded from LAMA3 gene. Laminins are a group of proteins that regulate growth, motility and cell adhesion. They are also involved in the formation and organization of basement membranes. Laminin 332 has a particularly important role in basement membrane underlying the epidermis. This membrane gives strength and elasticity to the skin and creates an additional barrier between the organism and its surrounding environment. 332 Laminin is a major component of anchoring filaments, which connect the two layers of the basement membrane and help keep the skin attached. Furthermore, it is likely that this protein is important in forming tissue wound healing and in the development of the cornea and tooth enamel.
They have been described at least two mutations in the gene responsible LAMA3 laryngo- onycho cutaneous syndrome. Mutations implicated result an abnormally short version of the alpha subunit-3a laminin 332 while 3b1 and 3b2 alpha-alpha are normal. Laminin proteins containing altered alpha subunit can not effectively attach the epidermis to the underlying layers of the skin or regulate wound healing. These abnormalities result in 332 laminin chronic skin ulcer and overgrowth of tissue characteristic of LOC syndrome. The inability of laminin 332 to perform its other functions leads to anomalies of nails and teeth. LOC syndrome is considered a subtype of epidermolysis bullosa binding. It is considered that mutations in the gene LAMA3 affect only the alpha-3a version of the alpha subunit lead to LOC syndrome, whereas mutations also affect other versions of the alpha subunit lead to junctional epidermolysis bullosa.
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 syndrome laryngo- onycho cutaneous (LOC), by complete PCR amplification of the exons of the gene LAMA3, 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).