Mowat-Wilson syndrome ..., (Mowat-Wilson syndrome) - Gen ZEB2

The Mowat-Wilson syndrome is a genetic disorder that affects many parts of the body. The main symptoms of this process include distinctive facial features, mental retardation, developmental delay, an intestinal disorder called Hirschsprung disease and other birth defects.

Children with Mowat-Wilson syndrome have a square - shaped face with sunken eyes and wide apart, broad nasal bridge with the tip of the rounded nose, a prominent and pointed chin, big eyebrows and earlobes high ears with a dimple in center. People usually have an expression with a smile open mouth and usually have a kind and happy personality. Often the syndrome is associated with microcephaly, structural brain abnormalities and mental retardation moderate to profound. Other signs include absent or severely impaired speech, often using sign language to communicate. If speech develops, it is delayed until mid-childhood or later. Children with Mowat-Wilson syndrome also have delayed development of motor skills such as sitting, standing and walking. More than half of people with the disease are born with an intestinal disorder called Hirschsprung disease that causes severe constipation and intestinal obstruction. Other characteristics of Mowat-Wilson syndrome include short stature, seizures, heart defects , and urinary and genital tract. Less commonly, the disease can also affect the eyes, teeth, hands, and skin pigmentation.

This process is due to mutations in the gene ZEB2 (zinc finger E-box binding homeobox 2), located on the long arm of chromosome 23 (2q22.3), encoding a protein transcription factor, which means that binds to specific regions of DNA and helps to control the expression of specific genes. This protein plays a critical role in the formation of many organs and tissues before birth. The ZEB2 protein is active in many cell types before birth. It seems to be especially important for the development of the neural crest, a group of cells resulting in many tissues and organs in early embryonic development. The neural crest cells migrate to form parts of the nervous system, endocrine glands that produce hormones, pigment cells, smooth muscle and other tissues in the heart, and many tissues in the face and skull. The ZEB2 protein is also active in cells not derived from the neural crest. For example, this protein is involved in the development of digestive tract, skeletal muscle, kidney and other organs.

They have identified more than 180 mutations in the gene ZEB2 in people with Mowat-Wilson syndrome. These mutations inactivate almost always a copy of the gene. In some cases, the entire gene is deleted. In other cases, mutations in the gene give rise to the synthesis of an abnormally short, nonfunctional version of the protein. A deficiency of this protein alters the normal development of many organs and tissues before birth. Abnormal development of the structures derived from the neural crest, such as the nervous system and facial features, is the source of many of the signs and symptoms of Mowat-Wilson syndrome. The role of ZEB2 protein in the development of the nerves that control the digestive tract may help explain why many people affected also have Hirschsprung's disease, an intestinal disorder that causes severe constipation, intestinal obstruction, enlarged colon.

The Mowat-Wilson syndrome is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient to cause the alteration. Most cases of this disorder are due to new mutations in the gene that occur during the formation of reproductive cells or early embryonic development. These cases occur in people with no history of disease in your family.  

Tests in IVAMI: in IVAMI perform detection of mutations associated with Mowat-Wilson syndrome, by complete PCR amplification of exons ZEB2 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).