Chromosome 14

FOXG1 syndrome

A deletion of genetic material from part of the long (q) arm of chromosome 14 can cause FOXG1 syndrome, which is a rare disorder that is characterized by impaired development and structural brain abnormalities. The region of chromosome 14 that is deleted includes the FOXG1 gene and several neighboring genes. Depending on which genes are involved, affected individuals may have additional signs and symptoms. 

The protein that is normally produced from the FOXG1 gene plays an important role in brain development before birth, particularly in a region of the embryonic brain known as the telencephalon. The telencephalon ultimately develops into several critical structures, including the largest part of the brain (the cerebrum), which controls most voluntary activity, language, sensory perception, learning, and memory. A loss of the FOXG1 gene disrupts normal brain development and contributes to the structural brain abnormalities and severe developmental problems that are characteristic of FOXG1 syndrome. It is unclear exactly how the loss of additional genes contributes to the signs and symptoms of this condition.

Multiple myeloma

A rearrangement (translocation) that moves genetic material from one of several other chromosomes to a region of chromosome 14 called 14q32 occurs in many people with multiple myeloma. This condition is a form of cancer that arises from plasma cells, which are a type of white blood cell. The translocation that involves chromosome 14 is somatic, which means it is acquired during a person's lifetime and is present only in certain cells. The translocation likely affects genes that help prevent cells from dividing too rapidly or in an uncontrolled way. Disruption of these genes may interfere with proper control (regulation) of cell growth and division (proliferation), resulting in the excessive proliferation of plasma cells that characterizes multiple myeloma.

Ring chromosome 14 syndrome

Ring chromosome 14 syndrome is caused by a chromosomal abnormality known as a ring chromosome 14 or r(14). A ring chromosome is a circular structure that occurs when a chromosome breaks in two places and the broken ends fuse together. Ring chromosome 14 syndrome is characterized by recurrent seizures (epilepsy) that begin early in life and intellectual disabilities, which typically range from moderate to severe. In people with ring chromosome 14 syndrome, the ring chromosome involves one of the two copies of chromosome 14 in some or all of their cells.

Several critical genes near the end of the q arm of chromosome 14 may be lost when the ring chromosome forms. The loss of these genes likely contributes to the major features of ring chromosome 14 syndrome, including intellectual disabilities and developmental delays. In addition, chromosomal rearrangements can disrupt several mechanisms that are involved in the regulation of gene activity (expression), which may also contribute to the features seen in people with ring chromosome 14 syndrome.

Other chromosomal conditions

A rare condition known as terminal deletion 14 syndrome causes signs and symptoms that are similar to those seen in people with ring chromosome 14 syndrome. Terminal deletion 14 syndrome is caused by the loss of several genes at the end (terminus) of chromosome 14q. In addition, some people with terminal deletion 14 syndrome lose or gain genetic material from another chromosome. People with this condition may have weak muscle tone (hypotonia), an unusually small head size (microcephaly), frequent respiratory infections, developmental delays, and learning difficulties.

Other changes in the number or structure of chromosome 14 can have a variety of effects, including delayed growth and development, distinctive facial features, and other health problems. Some of these genetic changes include an extra copy of a segment of chromosome 14 in every cell (partial trisomy 14), an extra copy of the entire chromosome in only some of the body's cells (mosaic trisomy 14), and deletions or duplications of part of chromosome 14. Full trisomy 14, which occurs when there is an extra copy of the entire chromosome 14 in all of the body's cells, is not compatible with life.

A chromosome abnormality called uniparental disomy (UPD) can also cause health problems. UPD occurs when people inherit both copies of a chromosome from one parent instead of one copy from each parent. The q arm of chromosome 14 contains some genes that are active only when they are inherited from the mother (maternal) and other genes that are active only when they are inherited from the father (paternal). Therefore, people who have two paternal copies or two maternal copies of chromosome 14 are missing some functional genes and have an extra copy of others.

When both copies of chromosome 14 are inherited from the mother, the phenomenon is known as maternal UPD 14. Maternal UPD 14 is associated with premature birth, slow growth before and after birth, short stature, developmental delays, small hands and feet, and early puberty. When both copies of the chromosome are inherited from the father, the phenomenon is known as paternal UPD 14. Paternal UPD 14 is associated with an excess of amniotic fluid (which surrounds the baby before birth); abnormalities of the abdominal wall; distinctive facial features; a small, bell-shaped chest with short ribs; and developmental delays. Both maternal UPD 14 and paternal UPD 14 appear to be rare.

Other cancers

Translocations of genetic material between chromosome 14 and other chromosomes have been associated with the development of other cancers. As with multiple myeloma, studies suggest that these translocations disrupt genes that are critical for keeping cell proliferation under control. Unregulated cell division can lead to the development of cancer.

Translocations that involve chromosome 14 have also been found in people with cancers of blood-forming cells (leukemias), cancers of immune system cells (lymphomas), and several related diseases. For example, Burkitt lymphoma, a cancer of white blood cells that occurs most often in children and young adults, is associated with a translocation between chromosomes 8 and 14. Another type of lymphoma, called follicular lymphoma, is often associated with a translocation between chromosomes 14 and 18.