Pitt-Hopkins syndrome ... (Pitt-Hopkins syndrome) - TCF4 gene.

The Pitt-Hopkins syndrome is a disorder characterized by mental retardation and developmental delay, moderate intensity deep, breathing problems, epilepsy, and distinctive facial features.

People with Pitt-Hopkins syndrome have profound intellectual disability and developmental delay. Most sufferers do not learn to walk unassisted. Generally, people with this disease do not get to talk although some can learn to say a few isolated words. Breathing problems in people with the syndrome are characterized by episodes of hyperventilation, followed by periods of apnea. These episodes can cause a lack of blood oxygenation, causing cyanosis. In some cases, lack of oxygen can cause loss of consciousness. Some seniors with Pitt-Hopkins syndrome have distal ends rounded and broad fingers in both hands, and feet because of recurrent episodes of hypoxia. Respiratory problems occur only when the person is awake and generally first appear within the first decade of life. Episodes of hyperventilation and apnea may be caused by emotions from excitement, anxiety or fatigue. Epilepsy occurs in most people with the syndrome and usually begins in childhood, although it may be present from birth. In addition, people with this syndrome have distinctive facial features include thin eyebrows, sunken eyes, prominent nose with a high nasal bridge, Cupid 's bow, a wide mouth with thick lips and widely spaced teeth. The ears are usually thick and cup - shaped. Children with this syndrome usually have a happy, excitable behavior with frequent smile, and flapping movements of the hands. However, they can also express anxiety and behavioral problems. Other characteristics of Pitt-Hopkins syndrome may include constipation and other gastrointestinal problems, small hands and feet, one crease across the palms, feet flat, microcephaly, myopia, strabismus, short stature, and lower brain abnormalities . Men with Pitt-Hopkins syndrome may have an unusually small or undescended penis.

This process is due to mutations in the gene TCF4, located on the long arm of chromosome 18 (18q21.1). This gene encodes a protein that interacts with other proteins and then binds to specific DNA regions to help control the activity of many genes. By action of DNA binding and gene control, this protein is a transcription factor. This protein plays a role in the maturation of cells to perform specific functions of cell differentiation and self - destruction of cells.

They have identified at least 50 mutations in the gene that cause TCF4 Pitt-Hopkins syndrome. These mutations prevent the protein can bind DNA and control the activity of certain genes. These changes, in particular the inability of the protein for controlling the activity of genes involved in nervous system development, contribute to the signs and symptoms of Pitt-Hopkins syndrome. Furthermore, as other proteins interacting with protein TCF4 to perform their specific functions, when the protein is nonfunctional TCF4, these other proteins are also can act normally. It is also likely that the loss of normal proteins that bind to non - functional proteins TCF4 contribute to the characteristics of this disease. It is believed that the loss of a particular protein, the protein Ascl1 is associated with respiratory problems in people with Pitt-Hopkins syndrome.

This disease is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient to cause the disorder. Most cases of this disease are the result of 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 Pitt-Hopkins syndrome, by complete PCR amplification of the exons of the gene TCF4, 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).