Last updated:
10/23/2024
Years published: 2010, 2013, 2016, 2019, 2023, 2024
NORD gratefully acknowledges Gioconda Alyea, MD (FMG), MS, National Organization for Rare Disorders and Jeffrey A. Kuller, MD, Professor of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Duke University Medical Center, for assistance in the preparation of this report.
The age of onset, specific symptoms, disease progression and severity of BSVD1 vary greatly from one person to another, even among members of the same family.
In some children, serious, life-threatening complications may occur in infancy; in others, only minor complications may occur and intelligence is unaffected. Other affected people may not develop any symptoms until well into adulthood. Affected individuals should talk to their physicians and medical team about their specific medical history and associated symptoms.
Symptoms that may occur in individuals with BDSV1 include:
Some affected individuals may have additional symptoms sometimes associated with variants in the COL4A1 gene. For more information, see the COL4A1-related disorders in the Disorders with Similar Symptoms section below.
BSVD1 is caused by variants in the COL4A1 gene. The COL4A1 gene contains instructions for creating a protein known as collage type IV. Collagen type IV is essential for the proper strength and function of the vascular basement membrane, which is the thin membrane that lines blood vessels. Variants in the COL4A1 gene can result in deficient levels or defective function of collagen type IV, which, in turn, results in structural weakening of the vascular basement membrane predisposing blood vessels to damage or rupture. Because the blood vessels are structurally weakened, environmental factors such as trauma (including birth trauma in infants with a COL4A1 variant) are much more likely to cause rupture or damage to the vessels. Damaged blood vessels within the skull result in bleeding on the brain or lack of blood flow (ischemia) to the brain and, subsequently, damage to brain tissue. The cavities or cysts that characterize porencephaly form at the sites of brain tissue damage.
Inheritance is autosomal dominant. Dominant genetic disorders occur when only a single copy of a disease-causing gene variant is necessary to cause the disease. The gene variant can be inherited from either parent or can be the result of a new (de novo) changed gene in the affected individual that is not inherited. The risk of passing the gene variant from an affected parent to a child is 50% for each pregnancy. The risk is the same for males and females.
Most individuals with BDSV1 have a parent with a disease-causing variant in the COL4A1 gene. In an unknown number of cases, the COL4A1 variant occurs randomly for no apparent reason (de novo) and is not inherited from a parent.
BDSV1 affects males and females in equal numbers. The incidence of the disorder in the general population is unknown. This condition may go undiagnosed or misdiagnosed, making it difficult to determine the true frequency.
A diagnosis of BDSV1 may be suspected based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests such as advanced imaging techniques. Such imaging techniques may include computerized tomography (CT) scanning and magnetic resonance imaging (MRI). During CT scanning, a computer and X-rays are used to create a film showing cross-sectional images of certain tissue structures. An MRI uses a magnetic field and radio waves to produce cross-sectional images of organs and bodily tissues.
A diagnosis can be confirmed by molecular genetic testing, in which a person’s DNA is tested for variants in the COL4A1 gene. Molecular genetic testing for this disorder is available on a clinical basis.
The treatment for BDSV1 is geared toward the specific symptoms that are present in each individual. For example, treatment may include physical therapy, speech therapy, anti-convulsant medications for seizures and a shunt to treat hydrocephalus by draining excess fluid from the skull. Individuals with high blood pressure (hypertension) must receive appropriate therapy because of the increased risk of stroke.
Early intervention is important in ensuring that children with BDSV1 reach their highest potential. Services that may be beneficial for some affected individuals include medical, social and/or vocational services such as special remedial education.
Smoking, which increases the risk of stroke, physical activities that can cause head trauma and the use of anti-clotting (anticoagulant) medications should be avoided.
Genetic counseling is recommended for affected individuals and their families. Other treatment is symptomatic and supportive.
Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact:
https://www.centerwatch.com/
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
Please note that some of these organizations may provide information concerning certain conditions potentially associated with this disorder (e.g., seizures).
JOURNAL ARTICLES
Vahedi K, Kubis N, Boukobza M, et al. COL4A1 mutation in a patient with sporadic, recurrent intracerebral hemorrhage. Stroke. 2007;38:1461-1464.
Van der Knaap MS, Smit LME, Barkhof F, et al. Neonatal porencephaly and adult stroke related to mutations in collagen IV A1. Ann Neurol. 2006;59:504-511.
Breedveld G, de Coo IF, Lequin MH, et al. Novel mutations in three families confirm a major role of COL4A1 in hereditary porencephaly. J Med Genet. 2006;43:490-495.
Gould DB, Phalan FC, van Mil SE, et al. Role of COLA41 in small-vessel disease and hemorrhagic stroke. N Eng J Med. 2006;354:1489-1496.
Gould DB, Phalan FC, Breedveld GJ, et al. Mutations in Col4a1 cause perinatal cerebral hemorrhage and porencephaly. Science. 2005;308:1167-1171.
INTERNET
Plaisier E, Ronco P. COL4A1-Related Disorders. 2009 Jun 25 [Updated 2016 Jul 7]. In: Adam MP, Everman DB, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK7046/ Accessed Nov 30, 2022.
National Institute of Neurological Disorders and Stroke. Porencephaly Information Page. Last reviewed July 25, 2022. Available at: https://www.ninds.nih.gov/Disorders/All-Disorders/Porencephaly-Information-Page Accessed Nov 30, 2022.
van Bogaert P. Porencephaly. Orphanet. June 2019. Available at: https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=99810 Accessed Nov 30, 2022.
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