Acute urinary retention due to a novel collagen COL4A1 mutation. This blood vessel abnormality can cause episodes of bleeding within the eyes following any minor trauma to the eyes, leading to temporary vision loss. Interestingly, COL4A1 and COL4A2 mutations appear to lead to generally similar outcomes although COL4A2 mutations occur less frequently. COL4A1 -related brain small-vessel disease is part of a group of conditions called the COL4A1 -related disorders. Prenatal clinical manifestations in individuals with COL4A1/2 variants. Role of COL4A1 in basement-membrane integrity and cerebral small-vessel disease. When a mutation occurs in one of these genes, the rope does not wind up properly and it stays inside the cell. Phenotypic spectrum of COL4A1 mutations: porencephaly to schizencephaly. (1987) 8:4216. So far, it appears as though mutations in COL4A1 and COL4A2 lead to identical disease, however, for reasons that are not yet understood, mutations in COL4A2 are much less frequent than those in COL4A1. Lenses corrected for hypermetropia. U.S. Department of Health and Human Services, Brain small-vessel disease with hemorrhage. In most cases, an affected person has one parent with the condition. Type IV collagen networks play an important role in the basement membranes in virtually all tissues throughout the body, particularly the basement membranes surrounding the body's blood vessels (vasculature). The COL4A1 gene provides instructions for making one component of a protein called type IV collagen. Neuropsychological tests disclosed language delay and learning difficulties requiring speech therapy at the age of 9 years. 2018;61:765-772. Washington, DC 20036 2015;84:918-926. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4351667/, Meuwissen ME, Halley DJ, Smit LS, et al. The severity of the condition varies greatly among affected individuals. Depending on the cell type that acquires the mutation and when the mutation arises, the individual may have many or few cells with the mutation. This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Our review highlights that COL4A1 mutations can present for the first time in adult life with features of cerebral SVD, including subcortical hemorrhage and ischemic stroke, . Still other individuals may not develop any symptoms until well into adulthood. Am J Neuroradiol. For example, Type I collagen mutations cause Osteogenesis Imperfecta (brittle bone disease), Type II collagen mutations cause chondrodysplasias (defects of cartilage) and mutations in Type III collagen cause a form of Ehlers-Danlos Syndrome. Stay Informed With NORDs Email Newsletter, Launching Registries & Natural History Studies. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. 55 Kenosia Avenue Stroke is a leading cause of death and serious long-term disability in developed nations. Suggestive evidence for linkage to chromosome 13qter for autosomal dominant type 1 porencephaly. came with risks and was the hardest decision we had ever faced, yet we felt 100 Each child of an individual with a COL4A1-related disorder has a 50% chance of inheriting the pathogenic variant. Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, et al. This is not specific to COL4A1/A2-related disorders, and is a sign of many different types of muscle disease. 2017;57-58:29-44. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5328961/, Sondergaard CB, Nielsen JE, Hansen CK, Christensen H. Hereditary cerebral small vessel disease and stroke. [Hereditary angiopathy with nephropathy, aneurysms and muscle cramps (HANAC): a new basement membrane-disease associated with mutations of the COL4A1 gene]. In people with HANAC syndrome, angiopathy affects several parts of the body. Email: [emailprotected], Some current clinical trials also are posted on the following page on the NORD website: These protein networks are the main component of basement membranes, which are thin sheet-like structures that separate and support cells in many tissues.
(2017) 5758:2944. Jeanne M, Gould DB. Meuwissen MEC, Halley DJJ, Smit LS, Lequin MH, Cobben JM, De Coo R, et al. Collagen alpha-1(IV) chain (COL4A1) is a protein that in humans is encoded by the COL4A1 gene on chromosome 13. These proteins have very restricted expression and Alport Syndrome primarily affects the kidneys with variable involvement of the eye and cochlea (hearing). This variant highlights that the COL4A1 mutation should be sought in cases of familial ophthalmologic pathologies associated with congenital porencephaly or early onset leukoencephalopathy. There are no standardized treatment protocols or guidelines for affected individuals. Some of these patients have been described as having HANAC syndrome, which is an acronym for hereditary angiopathy, nephropathy, aneurysms, and muscle cramps. Since fewer than 100 families have been reported, the exact prevalence of COL4A1-related disorders is not well-established. The age of onset, severity, specific symptoms and disease progression varies greatly from one person to another, even among members of the same family. Until just this year, her 16-year-old daughter Emily, who #1 Ranked Childrens Hospital by U. S. News & World Report. Received: 06 January 2020; Accepted: 01 July 2020; Published: 11 September 2020. The variant was found in IV-3 and IV-5 and not in asymptomatic relatives (III-4, IV-1, IV-4). She was struggling to advance both cognitively and physically because of uncontrolled epilepsy. Lecordier S, Manrique-Castano D, El Moghrabi Y, ElAli A. In some people, serious, life-threatening complications may occur in infancy; in others, only minor complications may occur and intelligence is unaffected. Drugs that prevent irregular heartbeats (anti-arrhythmic medications) are used to treat supraventricular arrythmia. Seattle, WA: University of Washington, Seattle; 1993-. Bone. Gould Syndrome is an ultra rare genetic, multi-system disorder. Surgery or endovascular therapy can be used to treat intracranial hemorrhage. Role of COL4A1 in small-vessel disease and hemorrhagic stroke. BMC Med Genet. Molecular genetic testing can detect variations in the COL4A1 and COL4A2 genes that cause these disorders, but is available only as a diagnostic service at specialized laboratories. PS and NL: followed III-3 at the Erasme Neurology outpatients clinic. Eur J Med Genet. eCollection 2022. He would separate the two halves of her brain by Gould DB, Phalan FC, van Mil SE, Sundberg JP, Vahedi K, Massin P, et al. Background: COL4A1 mutations cause familial porencephaly, infantile hemiplegia, cerebral small vessel disease (CSVD), and hemorrhagic stroke. Curr Opin Neurol. By continuing to use this website, you agree to the Terms of Service & Privacy Policy. Cereb Circ Cogn Behav. Careers. 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, and dystonia, a group of neurological disorders characterized by involuntary muscle contractions that force the body into abnormal, sometimes painful, movements and positions. Autosomal Dominant Familial Porencephaly Type I. Would you like email updates of new search results? J Genet Couns. For asymptomatic patients, cerebral and vessel imaging for aneurysm screening and ophthalmologic follow-up are indicated (2). 2010 The X and Y chromosomes are called the sex chromosomes and the rest all are called 'autosomes'. Genet Med. Some of the patient advocacy organizations listed in the Resources section below provide support and information to affected individuals and their families. Focke JK, Veltkamp R, Bauer P, Kraemer M. J Neurol. Figure 3. They are typically characterized by abnormal blood vessels in the brain (cerebral vasculature defects), eye development defects (ocular dysgenesis), muscle disease (myopathy), and kidney abnormalities (renal pathology); however, many other aspects of the syndrome including abnormalities affecting . (2007) 357:268795. (18) and Staals et al. Our experience with Boston Childrens was very different from the other places we had been for epilepsy and neurology treatment. Common variation in COL4A1/COL4A2 is associated with sporadic cerebral small vessel disease. Type IV Collagens and Basement Membrane Diseases: Cell Biology and Pathogenic Mechanisms. Dev Med Child Neurol. Individuals with HANAC syndrome also experience a variety of eye problems. The first time he came to meet us, Zeeva threw a sock at him. In most people, small vessel disease in the brain does not cause symptoms. J Neurol Sci. Various treatments have been reported in the medical literature as part of single case reports or small series of patients. Antiinflammatory therapy with canakinumab for atherosclerotic disease. . (D) III- 3Brain MRI showed small asymptomatic lesions in white matter. The COL4A1 gene mutations that cause COL4A1-related brain small-vessel disease result in the production of a protein that disrupts the structure of type IV collagen. Mutations in the gene have been linked to diseases of the brain, muscle, kidney, eye, and cardiovascular system. COL4A1 mutations and hereditary angiopathy, nephropathy, aneurysms, and muscle cramps.
Agenesis of the Corpus Callosum | National Institute of Neurological 2022 Oct 26;7(44):39680-39689. doi: 10.1021/acsomega.2c03360. Type IV collagen molecules attach to each other to form complex protein networks. 2009 Jun 25 [Updated 2016 Jul 7]. The size and location of cerebral cavities contributes to clinical variability. The risk of passing the non-working gene from an affected parent to an offspring is 50% for each pregnancy. These protein networks are the main components of basement membranes, which are thin sheet-like structures that separate and support cells in many tissues.
Aicardi-Goutieres syndrome - About the Disease - Genetic and Rare There are 28 different types of collagen in your body and mutations in the genes that encode these proteins lead to multiple, highly diverse diseases. COL4A1 -related brain small-vessel disease is characterized by weakening of the blood vessels in the brain.