Rothmund-Thomson syndrome ... (Rothmund-Thomson syndrome) - Gen RECQL4.
The Rothmund-Thomson syndrome is a rare disease that affects many parts of the body, especially the skin. Generally, affected individuals develop redness on the cheeks between 3 and 6 months old. Over time the rash spreads to the arms and legs, causing irregular discoloration of skin atrophy and skin areas telangiectasias. These skin problems persist for life and are collectively known as poikiloderma.
Syndrome Rothmund-Thomson also characterized by eyelashes, eyebrows and thinning hair, slow growth and small stature, abnormalities of the teeth and nails, and gastrointestinal problems in childhood and chronic diarrhea and vomiting. Some affected children develop cataracts that affect vision. In addition, many affected individuals have skeletal abnormalities including absence or malformation of bones, osteopenia and osteoporosis. Some of these abnormalities affect the development of the bones in the forearms and thumbs. People with Rothmund-Thomson syndrome have an increased risk of developing cancer, particularly osteosarcoma. These bone tumors most often develop during childhood or adolescence. Other common types of skin cancer in individuals with Rothmund-Thomson syndrome of include basal cell carcinoma and squamous cell carcinoma.
Signs and symptoms varied Rothmund-Thomson syndrome of overlap with features of other disorders such as Baller-Gerold syndrome and syndrome Rapadilino. These syndromes are also characterized by defects radio, skeletal abnormalities and slow growth. All of these diseases may be due to mutations in the same gene. Based on these similarities, it is investigated if Rothmund-Thomson syndrome, Baller syndrome-Gerold syndrome Rapadilino are separate or part of a single syndrome signs and symptoms overlap alterations.
This process is due to mutations in the gene RECQL4, located on the long arm of chromosome 8 (8q24.3). This gene encodes a member of a family of proteins called helicases RecQ. Helicases are enzymes that bind to DNA and temporally unrolling the two strands coiled DNA molecule. This unwinding is necessary for copy DNA in preparation for cell division and to repair damaged DNA. Because the RecQ helicases maintain the structure and integrity of DNA, known as the "guardian of the genome". The RECQL4 protein is active on various types of cells before and after birth. It is likely that this protein is particularly important in the cells of developing bones and skin. It has also been found in enterocytes lining the intestine and absorb nutrients.
They have identified more than 40 mutations in the gene RECQL4 in people with Rothmund-Thomson syndrome. These mutations probably inhibit any RECQL4 encoding protein or encoding lead to an abnormally short, nonfunctional version of the protein. Deficiency of this protein may alter DNA replication and repair, causing widespread damage over time in the genetic information of a person. Further studies to determine how these changes result in the characteristics of Rothmund-Thomson syndrome are needed.
This disease is inherited in an autosomal recessive pattern, that is, 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 Rothmund-Thomson syndrome, by complete PCR amplification of exons RECQL4 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).