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Disease Profile

X-linked periventricular heterotopia

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

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ICD-10

#N/A

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Heterotopia periventricular X-linked dominant; Periventricular nodular heterotopia 1; Heterotopia familial nodular;

Categories

Congenital and Genetic Diseases; Nervous System Diseases

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.

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]

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]

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.

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

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]

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

    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]

    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

      Organizations Providing General Support

        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

          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

              References

              1. 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. https://www.amjmed.com/article/0002-9343(81)90341-7/abstract.
              2. 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. https://connection.ebscohost.com/c/articles/20448079/ehlers-danlos-syndrome-periventricular-nodular-heterotopia-spanish-family-single-flna-mutation.
              3. Sheen VL, Bodell A & Walsh CA. X-Linked Periventricular Heterotopia. GeneReviews. September 17, 2015; https://www.ncbi.nlm.nih.gov/books/NBK1213/.
              4. Periventricular heterotopia. Genetics Home Reference (GHR). November, 2007; https://ghr.nlm.nih.gov/condition/periventricular-heterotopia.
              5. 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/.
              6. Hui Chen M & Wals CA. FLNA-Related Periventricular Nodular Heterotopia. GeneReviews. September 17, 2015; https://www.ncbi.nlm.nih.gov/books/NBK1213/.

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