X-linked periventricular heterotopia

Title

Other Names:

Heterotopia periventricular X-linked dominant; Periventricular nodular heterotopia 1; Heterotopia familial nodular; Heterotopia periventricular X-linked dominant; Periventricular nodular heterotopia 1; Heterotopia familial nodular; Nodular heterotopia bilateral periventricular; NHBP; Bilateral periventricular nodular heterotopia; BPNH; PVNH1 See More

Categories:

Congenital and Genetic Diseases; Nervous System Diseases

Summary Summary

X-linked periventricular heterotopia or FLNA-related periventricular nodular heterotopia is a genetic disorder in which nerve cells in the brain do not migrate properly during early fetal development (neuronal migration disorder). It is characterized by the presence of clumps or clusters of neurons near the brain's ventricles (fluid-filled cavities). Most individuals with this genetic disorder are female. It is is often lethal in males. Symptoms typically begin with seizures in the middle teen years. Intelligence is usually normal, although mild intellectual disability, including difficulty with reading and spelling may occur. Individuals appear to be at increased risk for stroke and other vascular/coagulation problem. Some people also have hyperflexible joints and vascular anomalies (aortic dilation and other), symptoms also seen in the Ehlers-Danlos syndrome.[8155][8156]^[1] X-linked periventricular heterotopia is caused by mutations in the FLNA gene and is inherited in an X-linked dominant fashion.^[1]^[2] Treatment is dependent on the signs and symptoms present in each individual and may include anti-seizure medications.^[1]^[3]

The Ehlers-Danlos variant (PVNH4) or Ehlers-Danlos syndrome (EDS) with periventricular heterotopia is now considered to be the same as X-linked periventricular heterotopia type 1 (PVNH1) and it is not part of the EDS subtypes under the new 2017 classification of EDS.

Last updated: 4/20/2017

Symptoms Symptoms

The signs and symptoms of X-linked periventricular heterotopia usually begin in the teenage years with seizures. Although intelligence is usually normal in individuals with this condition, some may have mild intellectual disability, including difficulties with reading and spelling (dyslexia). There additionally may be a greater risk for cardiovascular disease, stroke, and other vascular or coagulation (blood clotting) problems.^[1]^[2]

Other signs and symptoms may include:^[1]^[3]

Cardiovascular findings (patent ductus arteriosus, dilatation and rupture of the thoracic aorta, atrial and ventricular septal defects, weakness of the cardiac valves)
Congenital strabismus
Shortened digits (fingers and toes)
Hyperflexible joints
Pulmonary (lung) disease
Skin that is too elastic

Less commonly, individuals with X-linked periventricular heterotopia may have other brain findings, gastrointestinal symptoms, and musculoskeletal symptoms similar to individuals with Ehlers-Danlos syndrome.^[1]^[2]^[3]

Males with this condition experience much more severe symptoms than females, and in most cases die before birth.^[1]^[2]

Last updated: 4/20/2017

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Abnormality of neuronal migration	-
Abnormality of the coagulation cascade	-
Bicuspid aortic valve	-
Heterotopia	-
Intellectual disability, mild	-
Patent ductus arteriosus	-
Seizures	-
Stroke	-
X-linked dominant inheritance	-

Last updated: 6/1/2017

Cause Cause

X-linked periventricular heterotopia is caused by mutations in the FLNA gene. This gene provides instructions for making the protein filamin A, which helps build the network of protein that gives structure to cells and allows them to change shape and move (cytoskeleton). Certain mutations in the FLNA gene result in an impaired filamin A protein that cannot perform this function, leading to a disruption of the normal migration patterns of neurons during brain development.^[2]

Last updated: 2/1/2017

Inheritance Inheritance

X-linked periventricular heterotopia is inherited in an X-linked dominant pattern. This means that the gene responsible for the condition is located on the X chromosome, and having only one mutated copy of the gene is enough to cause the condition.

Because males have only one X chromosome (and one Y chromosome) and females have two X chromosomes, X-linked dominant conditions affect males and females differently. Both males and females can have an X-linked dominant condition. However, because males don't have a second, working copy of the gene (as females do), they usually have more severe disease than females.

If a father has the mutated X-linked gene:

all of his daughters will inherit the mutated gene (they will all receive his X chromosome)
none of his sons will inherit the mutated gene (they only inherit his Y chromosome)

If a mother has the mutated X-linked gene, each of her children (both male and female) has a 50% chance to inherit the mutated gene.

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 (de novo). These cases occur in people with no history of the disorder in their family.^[2]^[4]

Last updated: 2/1/2017

Diagnosis Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Treatment Treatment

Although there is no cure for X-linked periventricular heterotopia, there may be ways to manage the signs and symptoms in each individual. Seizures are typically treated with antiepileptic medications. Given the risk for aortic or carotid dissection (leaking of blood into the artery wall), individuals with this condition may be advised to keep blood pressure within the normal range.

Additionally, it is recommended that individuals with X-linked periventricular heterotopia undergo carotid and abdominal ultrasound surveillance studies for aortic and carotid dissection and echocardiograms to monitor valvular abnormalities.^[1]

Last updated: 2/1/2017

Management Guidelines

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.

Do you have updated information on this condition? Let us know.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

The Christopher A. Walsh Laboratory is interested in the development of the cerebral cortex. Abnormal development of the cerebral cortex in humans results in epilepsy, autism, mental retardation, dyslexia, and other learning disorders, and perhaps some psychiatric conditions as well. Several of their projects are directed at trying to understand the basic biology of the cortex by studying the mutations that disturb its development. Conditions that they are currently researching include: double cortex syndrome, periventricular heterotopia, schizencephaly, perisylvian polymicrogyria and Walker Warburg syndrome. Click on the link above to access further information about this research.
The Research Portfolio Online Reporting Tool (RePORT) provides access to reports, data, and analyses of research activities at the National Institutes of Health (NIH), including information on NIH expenditures and the results of NIH-supported research. Although these projects may not conduct studies on humans, you may want to contact the investigators to learn more. To search for studies, enter the disease name in the "Text Search" box. Then click "Submit Query".

Organizations Organizations

Nonprofit support and advocacy groups bring together patients, families, medical professionals, and researchers. These groups often raise awareness, provide support, and develop patient-centered information. Many are the driving force behind research for better treatments and possible cures. They can direct people to research, resources, and services. Many groups also have experts who serve as medical advisors. Visit their website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

American Epilepsy Society
135 South LaSalle Street
Suite 2850
Chicago, IL 60603
Telephone: +1-312-883-3800
Fax: +1-312-896-5784
E-mail: info@aesnet.org
Website: https://www.aesnet.org/
Epilepsy Foundation
8301 Professional Place East
Suite 200
Landover, MD 20785-2238
Toll-free: 800-EFA-1000 (800-332-1000)
Telephone: 301-459-3700
Fax: 301-577-4941
E-mail: info@efa.org
Website: http://www.epilepsyfoundation.org
PVNH Support & Awareness
206-1082 West 8th Avenue
Vancouver British Columbia, V6H 1C4 Canada
Telephone: +1-604-714-1222
E-mail: info@pvnhsupport.com
Website: http://pvnhsupport.com/

Do you know of an organization? Send us your suggestions.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Genetics Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by GeneTests, the American College of Medical Genetics, and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

Genetics Home Reference (GHR) contains information on X-linked periventricular heterotopia. This website is maintained by the National Library of Medicine.
The National Institute of Neurological Disorders and Stroke (NINDS) collects and disseminates research information related to neurological disorders. Click on the link to view information on this topic.

In-Depth Information

The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss X-linked periventricular heterotopia. Click on the link to view a sample search on this topic.

Selected Full-Text Journal Articles

Lange M, Kasper B, Bohring A, et al. 47 patients with FLNA associated periventricular nodular heterotopia. Orphanet Journal of Rare Diseases. 2015;10:134.

Related Diseases Related Diseases

The following diseases are related to X-linked periventricular heterotopia. If you have a question about any of these diseases, you can contact GARD.

Periventricular heterotopia

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

Can you provide me with information about X-linked periventricular heterotopia? Where can I access articles and case studies related to this condition? See answer

Have a question? Contact a GARD Information Specialist.

References References

Sheen VL, Bodell A & Walsh CA. X-Linked Periventricular Heterotopia. GeneReviews. September 17, 2015; https://www.ncbi.nlm.nih.gov/books/NBK1213/.
Periventricular heterotopia. Genetics Home Reference (GHR). November, 2007; https://ghr.nlm.nih.gov/condition/periventricular-heterotopia.
Lange M, Kasper B, Bohring A, et al. 47 patients with FLNA associated periventricular nodular heterotopia. Orphanet Journal of Rare Diseases. October 2015; 10(134):https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4608144/.
Hui Chen M & Wals CA. FLNA-Related Periventricular Nodular Heterotopia. GeneReviews. September 17, 2015; https://www.ncbi.nlm.nih.gov/books/NBK1213/.