Kindler syndrome ... (Kindler syndrome) - Gen FERMT1
Kindler syndrome is a rare type of epidermolysis bullosa, a group of genetic diseases that cause the skin is very fragile and easily off.
Since early childhood, people with Kindler syndrome have skin blisters, especially on the back of the hands and toes. Eventually, the blisters occur less frequently, but repeated blistering hands can cause scars that fuses the skin between the toes. Affected individuals also develop a thin skin, papery, which begins in the hands and feet and then affects other parts of the body. Other skin anomalies that occur Kindler syndrome include changes in skin pigmentation and telangiectasia, a combination known as poikiloderma. In some affected individuals, hyperkeratosis occurs. In addition, people with Kindler syndrome can also be highly sensitive to ultraviolet rays of the sun and be prone to sunburn.
Kindler syndrome can also affect the lining of the mouth, eyes, esophagus, intestines, genitals and urinary system, causing these tissues become very fragile and easily damaged. People usually develop severe gum disease that can lead to premature tooth loss. In addition, the conjunctiva may catch fire and damage to the cornea may affect vision. Stricture of the esophagus, causing difficulty swallowing that gets worse over time. Some affected individuals develop health problems related to inflammation of the colon (colitis) or damage to the lining of the vagina, anus or urethra.
Kindler syndrome increases the risk of developing squamous cell carcinoma. This cancer arises from squamous cells found in the epidermis and mucous. In people with Kindler syndrome, squamous cell carcinoma occurs most commonly in the skin, lips and oral mucosa.
This process is due to mutations in the FERMT1 (fermitin family member 1) gene, located on the short arm of chromosome 20 (20p12.3). This gene encodes kindlin-1 protein, a protein found in the epithelial cells. In the skin, kindlin-1 plays a critical role in keratinocytes, the principal component of the epidermis. The kindlin-1 is involved in several important cellular functions, including cell growth and proliferation, cell-matrix adhesion and cell migration.
They described over 70 mutations in the gene FERMT1 in people with Kindler syndrome. The mutations described so far have been: missense mutations (25), and cutting mutations -splicing- connection (9), small deletions (13), small insertions (6), small indels (1), larger deletions (3) and inserts / higher duplications (1). Most mutations in the gene FERMT1 inhibit the synthesis of any kindlin-1 functional protein. The absence of this protein alters many essential cellular functions. For example, keratinocytes without kindlin-1 have an abnormal structure and can not grow or divide normally. They are also less able to bind the epidermis to the dermis. These changes cause the skin to become fragile and prone to blistering. Similarly, the absence of kindlin-1 in epithelial cells of the mucosa causes damage that make these tissues become extremely brittle. It is unclear how kindlin-1 deficiency is associated with squamous cell carcinoma in people with Kindler syndrome.
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 in IVAMI: in IVAMI perform detection of mutations associated with Kindler syndrome, by complete PCR amplification of exons FERMT1 gene, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated card blood sample desiccated (IVAMI can mail the card to deposit the blood sample).