We're celebrating
40 years!
Last updated:
02/03/2023
Years published: 2010, 2013, 2016, 2019, 2023
NORD gratefully acknowledges 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.
Autosomal dominant porencephaly type I is a rare genetic disorder in which fluid-filled cysts and cavities develop on the surface of the brain. Autosomal dominant porencephaly type I is caused by changes (mutations or pathogenic variants) in the COL4A1 gene. Affected individuals are predisposed to damage to small blood vessels, including the small vessels within the brain. The signs and symptoms of this disorder vary greatly from one individual to another but may include weakness or paralysis of one side of the body (hemiparesis or hemiplegia), seizures, varying degrees of cognitive impairment and migraines.
Variants in the COL4A1 gene also cause at least two other disorders – brain small vessel disease with hemorrhage and HANAC (hereditary angiopathy with neuropathy, aneurysms, and muscle cramps) syndrome. Researchers now know that these three disorders represent a spectrum or continuum of disease with overlapping features.
The age of onset, specific symptoms, disease progression and severity of autosomal dominant porencephaly type I vary greatly from one individual to another, even among members of the same family. The term porencephaly refers to the formation of fluid-filled cysts or cavities on the surface of the brain. The size and exact locations of such cysts and cavities contribute to the clinical variability of this disorder. In some children, serious, life-threatening complications may occur in infancy; in others, only minor complications may occur and intelligence is unaffected. Still other individuals may not develop any symptoms (asymptomatic) 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 autosomal dominant type I porencephaly include migraines, weakness or paralysis of one side of the body (hemiparesis or hemiplegia), seizures, stroke, varying degrees of intellectual disability and dystonia, a group of neurological disorders characterized by involuntary muscle contractions that force the body into abnormal, sometimes painful, movements and positions.
Additional features that may be associated with autosomal dominant porencephaly type I include poor or absent speech development, facial paralysis (paresis), involuntary muscle spasms (spasticity) that result in slow, stiff, rigid movements, visual field defects and hydrocephalus, a condition in which accumulation of excessive cerebrospinal fluid in the skull causes pressure on the tissues of the brain, resulting in a variety of symptoms.
Some individuals with autosomal dominant porencephaly type I may have additional symptoms sometimes associated with variants in the COL4A1 gene. For more information, see the COL4A1-related disorders in the Related Disorders section below.
This genetic form of porencephaly is caused by variants in the COL4A1 gene and is inherited in an autosomal dominant pattern. Most individuals with autosomal dominant porencephaly type I have a parent with a pathogenic variant in the COL4A1 gene. In an unknown number of cases, the COL4A1 variant occurs randomly for no apparent reason (de novo).
Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Dominant genetic disorders occur when only a single copy of an altered gene is necessary for the appearance of the disease. The altered gene can be inherited from either parent or can be the result of a new variant (gene change) in the affected individual. The risk of passing the altered gene from affected parent to offspring is 50 percent for each pregnancy. The risk is the same for males and females.
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. Pathogenic variants in the COL4A1 gene 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.
Autosomal dominant porencephaly type I affects males and females in equal numbers. The incidence of the disorder in the general population is unknown. Autosomal dominant porencephaly type I may go undiagnosed or misdiagnosed, making it difficult to determine the true frequency of this disorder.
A diagnosis of autosomal dominant porencephaly type I is 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. A MRI uses a magnetic field and radio waves to produce cross-sectional images of particular 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 that cause autosomal dominant porencephaly type I. Molecular genetic testing for this disorder is available on a clinical basis.
The treatment of autosomal dominant porencephaly type I 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. Smoking, which also increases the risk of stroke, physical activities that can cause head trauma and the use of anti-clotting (anticoagulant) medications should also be avoided.
Early intervention is important in ensuring that children with autosomal dominant porencephaly type I 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.
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: prpl@cc.nih.gov
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.
NORD strives to open new assistance programs as funding allows. If we don’t have a program for you now, please continue to check back with us.
NORD and MedicAlert Foundation have teamed up on a new program to provide protection to rare disease patients in emergency situations.
Learn more https://rarediseases.org/patient-assistance-programs/medicalert-assistance-program/Ensuring that patients and caregivers are armed with the tools they need to live their best lives while managing their rare condition is a vital part of NORD’s mission.
Learn more https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/This first-of-its-kind assistance program is designed for caregivers of a child or adult diagnosed with a rare disorder.
Learn more https://rarediseases.org/patient-assistance-programs/caregiver-respite/