CHOPS syndrome ... (CHOPS syndrome: Cognitive impairment / Coarse facial features, Heart defects, Obesity, Pulmonary) - Gen AFF4.

The CHOPS syndrome is a disorder that involves multiple congenital anomalies. CHOPS (C ognitive impairment, c oarse facial features, H eart defects, O besity, lung - P ulmonary-), refers to the characteristics of the disease, including cognitive decline characteristic facial features, cardiac defects, obesity, lung problems , short and skeletal abnormalities.

Children with CHOPS syndrome have intellectual disabilities and delayed development of skills such as sitting and walking. Referring to the characteristic facial features these include a round face, thick hair, synophrys, bulging eyes with long lashes and a short nose. Most affected individuals have heart defects such as patent ductus arteriosus (PDA) and ventricular septal defect, which can lead to heart failure. People with CHOPS syndrome have abnormalities of the throat and airways causing obstructive sleep apnea. These abnormalities can also cause affected individuals accidentally inhaling food or liquid into the lungs, which can cause aspiration pneumonia and chronic lung disease. In addition, affected individuals are smaller in stature and are overweight. They also have skeletal differences including brachydactyly and unusual vertebrae. Other characteristics associated with CHOPS syndrome may include microcephaly, hearing loss, cataracts, the presence of a single kidney horseshoe and in affected males, cryptorchidism.

This process is due to mutations in the gene AFF4, located on the long arm of chromosome 5 (5q31). This gene encodes part of a protein complex called superelongación complex (SEC). This complex consists of a group of proteins responsible for controlling the elongation phase of transcription, wherein the RNA polymerase II catalyzes the production of the RNA strand. During embryonic development, this protein is involved in transcription, which is the first step in encoding proteins from genes. Returning to begin transcription of certain genes after pauses that normally occur during the process, the SEC helps ensure proper development progresses before birth.

Mutations identified the gene AFF4 in people with CHOPS syndrome, change amino acids in the protein AFF4. It is believed that these mutations lead to a AFF4 protein is not decomposed when no longer needed, so it is available AFF4 more protein than usual. Excess protein AFF4 interferes with normal breaks in transcription. This deregulation of transcription causes problems in the development of multiple organs and tissues, which leads to the signs and symptoms of CHOPS syndrome.

This disease is an autosomal dominant genetic pattern, which means that a copy of the altered gene in each cell is sufficient to express the disease. All known cases of CHOPS syndrome result of new mutations in the gene that occur during the formation of reproductive cells or early embryonic development. Affected individuals have no history of the disease in his family.

Tests in IVAMI: in IVAMI perform detection of mutations associated with Syndrome CHOPS, by complete PCR amplification of exons AFF4 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).