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

This disease is grouped under:

Periventricular heterotopia

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 (a neuronal migration disorder). It is characterized by the presence of clumps of neurons near the brain's ventricles. Most people with this disorder are female, as it can be lethal in males.

Symptoms typically begin with seizures in the teenage years. Intelligence is usually normal, but mild intellectual disability (including difficulty with reading and spelling) may occur. People with this condition also appear to be at increased risk for stroke and other vascular or coagulation (clotting) problems. Some people also have hyperflexible joints and vascular anomalies, which also occur in Ehlers-Danlos syndrome (EDS).^[1]^[2]^[3]

X-linked periventricular heterotopia is caused by mutations in the FLNA gene and is inherited in an X-linked dominant manner.^[3]^[4] Treatment depends on the symptoms in each person and typically includes anti-seizure medications.^[3]^[5]

EDS with periventricular heterotopia, previously considered a variant of EDS, is now considered to be the same as X-linked periventricular heterotopia type 1 (PVNH1) and is not included as an EDS subtype under the 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, 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.^[3]^[4]

Other signs and symptoms may include:^[3]^[5]

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

Less commonly, people with X-linked periventricular heterotopia may have other brain findings, gastrointestinal symptoms, and musculoskeletal symptoms similar to those seen in Ehlers-Danlos syndrome.^[3]^[4]^[5]

Males with this condition often have much more severe symptoms than females. IN many cases, males with this condition do not survive to birth.^[3]^[4]

Last updated: 4/20/2017

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 23 |

Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Abnormal bleeding	Bleeding tendency	0001892
Gastroesophageal reflux	Acid reflux Acid reflux disease Heartburn [ more ]	0002020
Hernia		0100790
Pyloric stenosis		0002021
Scoliosis		0002650
30%-79% of people have these symptoms
Abnormal heart valve morphology		0001654
Aortic regurgitation		0001659
Focal-onset seizure	Seizure affecting one half of brain	0007359
Joint hypermobility	Double-Jointed Flexible joints Increased mobility of joints [ more ]	0001382
Patent ductus arteriosus		0001643
Periventricular heterotopia		0007165
Thin skin		0000963
5%-29% of people have these symptoms
Aortic aneurysm	Bulge in wall of large artery that carries blood away from heart	0004942
Patellar dislocation	Dislocated kneecap	0002999
Shoulder dislocation		0003834
Percent of people who have these symptoms is not available through HPO
Abnormality of neuronal migration		0002269
Abnormality of the coagulation cascade		0003256
Bicuspid aortic valve	Aortic valve has two leaflets rather than three	0001647
Gray matter heterotopia		0002282
Intellectual disability, mild	Mental retardation, borderline-mild Mild and nonprogressive mental retardation Mild mental retardation [ more ]	0001256
Seizure		0001250
Stroke		0001297
X-linked dominant inheritance		0001423

Showing of 23 |

Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 7/1/2020

Do you have updated information on this disease? We want to hear from you.

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.^[4]

Last updated: 2/1/2017

Inheritance Inheritance

Inheritance of X-linked periventricular heterotopia is X-linked dominant. 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.

In rare cases, males with FLNA mutations survive to adulthood and father children.^[6] 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.^[4]^[6]

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.^[3]

Last updated: 2/1/2017

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare 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 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.

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, intellectual disability, 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

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s 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

Epilepsy Foundation
8301 Professional Place East
Suite 230
Landover, MD 20785
Toll-free: 800-332-1000 (24/7 Helpline)
Telephone: +1-301-459-3700
Fax: +1-301-577-2684
E-mail: contactus@efa.org
Website: https://www.epilepsy.com/
en Español 1-866-748-8008
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? We want to hear from you.

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

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.
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.

News & Events News & Events

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References References

Cupo, L & cols. Ehlers-Danlos syndrome with abnormal collagen fibrils, sinus of Valsalva aneurysms, myocardial infarction, panacinar emphysema and cerebral heterotopias. Am J Med. 1981; 71:1051-1058. http://www.amjmed.com/article/0002-9343(81)90341-7/abstract.
Gomez-Garre & cols. Ehlers-Danlos syndrome and periventricular nodular heterotopia in a Spanish family with a single FLNA mutation. J Med Genet. 43:232-237. http://connection.ebscohost.com/c/articles/20448079/ehlers-danlos-syndrome-periventricular-nodular-heterotopia-spanish-family-single-flna-mutation.
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/.