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Periventricular heterotopia is a condition in which nerve cells (neurons) do not migrate properly during the early development of the fetal brain, from about the 6th week to the 24th week of pregnancy. Heterotopia means "out of place." In normal brain development, neurons form in the periventricular region, located around fluid-filled cavities (ventricles) near the center of the brain. The neurons then migrate outward to form the exterior of the brain (cerebral cortex) in six onion-like layers. In periventricular heterotopia, some neurons fail to migrate to their proper position and form clumps around the ventricles.
Periventricular heterotopia usually becomes evident when seizures first appear, often during the teenage years. The nodules around the ventricles are then typically discovered when magnetic resonance imaging (MRI) studies are done. Affected individuals usually have normal intelligence, although some have mild intellectual disability. Difficulty with reading and spelling (dyslexia) has been reported in some people with periventricular heterotopia.
Less commonly, individuals with periventricular heterotopia may have more severe brain malformations, small head size (microcephaly), developmental delays, recurrent infections, blood vessel abnormalities, or other problems. Periventricular heterotopia may also occur in association with other conditions such as Ehlers-Danlos syndrome, which results in extremely flexible joints, skin that stretches easily, and fragile blood vessels.
Periventricular heterotopia is a rare condition. Its incidence is unknown.
Periventricular heterotopia is related to chromosome 5.
Mutations in the ARFGEF2 and FLNA genes cause periventricular heterotopia.
In most cases, periventricular heterotopia is caused by mutations in the FLNA gene. This gene provides instructions for producing the protein filamin A, which helps build the network of protein filaments (cytoskeleton) that gives structure to cells and allows them to change shape and move. Certain mutations in the FLNA gene result in an impaired FLNA protein that cannot perform this function, disrupting the normal migration patterns of neurons during brain development.
Periventricular heterotopia can also be caused by mutations in the ARFGEF2 gene. This gene provides instructions for making a protein that is involved in the movement (trafficking) of small sac-like structures (vesicles) within the cell. Vesicle trafficking is important in controlling the migration of neurons during the development of the brain. Mutations in the ARFGEF2 gene may disrupt this function, which could result in the abnormal neuronal migration seen in periventricular heterotopia.
Researchers believe that mutations in the FLNA or ARFGEF2 genes may also result in weakening of the attachments (adhesion) between cells that form the lining of the ventricles. A weakened ventricular lining could allow some neurons to form clumps around the ventricles while others migrate normally to the exterior of the brain, as seen in periventricular heterotopia.
In a few cases, periventricular heterotopia has been associated with abnormalities in chromosome 5. In each case, the affected individual had extra genetic material caused by an abnormal duplication of part of this chromosome. It is not known how this duplicated genetic material results in the signs and symptoms of periventricular heterotopia.
Changes involving this chromosome are associated with periventricular heterotopia.
Changes in these genes are associated with periventricular heterotopia.
Periventricular heterotopia can have different inheritance patterns. When this condition is caused by mutations in the FLNA gene, it is inherited in an X-linked dominant pattern.
A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. The inheritance is dominant if one copy of the altered gene in each cell is sufficient to cause the condition. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.
In X-linked periventricular heterotopia, males experience much more severe symptoms of the disorder than females, and in most cases die before birth.
In about 50 percent of cases of X-linked periventricular heterotopia, an affected person inherits the mutation from a mother who is also affected. Other cases may result from new mutations in the gene. These cases occur in people with no history of the disorder in their family.
Periventricular heterotopia caused by mutations in the ARFGEF2 gene is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Individuals with periventricular heterotopia in whom ARFGEF2 gene mutations have been identified have a severe form of the disorder, including microcephaly, severe developmental delay, and seizures beginning in infancy. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.
These resources address the diagnosis or management of periventricular heterotopia and may include treatment providers.
You might also find information on the diagnosis or management of periventricular heterotopia in Educational resources (http://ghr.nlm.nih.gov/condition/periventricular-heterotopia/show/Educational+resources) and Patient support (http://ghr.nlm.nih.gov/condition/periventricular-heterotopia/show/Patient+support).
General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).
To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.
You may find the following resources about periventricular heterotopia helpful. These materials are written for the general public.
You may also be interested in these resources, which are designed for healthcare professionals and researchers.
For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/gard).
autosomal ; autosomal recessive ; cell ; cerebral cortex ; chromosome ; cytoskeleton ; developmental delay ; disability ; duplication ; familial ; gene ; imaging ; incidence ; inheritance ; inherited ; magnetic resonance imaging ; microcephaly ; mutation ; neuronal migration ; protein ; recessive ; sex chromosomes ; syndrome ; teenage ; vesicle ; X-linked dominant
You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).
The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.