Copyright 2023 NORD National Organization for Rare Disorders, Inc. All rights reserved. Liu X, Yang Q, Tang L, He J, Tian D, Wang B, Xie L, Li C, Fan D. Front Neurol. In: Adam MP, Everman DB, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. NCI CPTC Antibody Characterization Program. 4 Both . 2015;17:843-853. https://www.nature.com/articles/gim2014210, Yoneda Y, Haginoya K, Kato M, et al. and transmitted securely. Zeeva woke up after a ten-hour procedure, opened her eyes, and it felt like we were seeing her for the first time. In the back of the eye, affected individuals have also twisting or distortion (tortuosity) of arteries in the retina (bilateral retinal arterial tortuosity) as part of the syndrome or as an isolated finding. 2017 Jan;66:100-103. doi: 10.1016/j.pediatrneurol.2016.04.010. In the human genome, there are 46 chromosomes. eCollection 2021. People with this condition may have a bulge in one or multiple blood vessels in the brain (intracranial aneurysms). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282239/. Facebook: https://www.facebook.com/Col4A1Foundation Please Note COL4A1-related brain small-vessel disease is characterized by weakening of the blood vessels in the brain. 2018;61:765-772. 1 Survivors often have a severely diminished quality of life, require long-term care, and are at high risk . Vahedi K, Alamowitch S. Clinical spectrum of type IV collagen (COL4A1) COL4A1 is an essential component for basal membrane stability and exon mutations of COL4A1 gene mutations are responsible for a broad spectrum of systemic manifestations characterized by small vessel involvement of variable severity, including neurological ( 1) [porencephaly ( 2 - 4 ), hemorrhage ( 2, 5 - 7) and aneurysms ( 8 )], ophthalmological Affected individuals have kidney disease (nephropathy) causing blood in the urine (hematuria) that can either be seen by the naked eye (gross hematuria) or only visible when tested (microscopic hematuria). Our experience with Boston Childrens was very different from the other places we had been for epilepsy and neurology treatment. 2015;84:918-926. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4351667/, Meuwissen ME, Halley DJ, Smit LS, et al. MedlinePlus links to health information from the National Institutes of Health and other federal government agencies. Dev Med Child Neurol. small vessel disease: a systematic review. Bone. U.S. Department of Health and Human Services, Brain small-vessel disease with hemorrhage. Supporting children in their development to reduce handicaps and combining their follow-up with parent counseling could be considered as an ideal approach. Type IV collagen molecules attach to each other to form complex protein networks. Eur J Paediatr Neurol. More info about Gould Syndrome is available at https://rarediseases.org/rare-diseases/col4a1-a2-related-disorders/. Zeevas brain to treat a cyst in her brain caused by porencephaly. (D) III- 3Brain MRI showed small asymptomatic lesions in white matter. (19). doi: 10.1212/WNL.0000000000006567, PubMed Abstract | CrossRef Full Text | Google Scholar, 2. Some individuals develop cysts on the kidney. 2008 May;192(5):971-84; discussion 984-6. Plaisier E, Chen Z, Gekeler F, Benhassine S, Dahan K, Marro B, Alamowitch S, Paques M, Ronco P. Am J Med Genet A. Gould Syndrome is often 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 the structure of the brain (cerebral cortical abnormalities) and lung (pulmonary) abnormalities continue to emerge and the full spectrum is still uncharacterized. Suggestive evidence for linkage to chromosome 13qter for autosomal dominant type 1 porencephaly. We provide education, advocacy, and resources for families and individuals affected. doi: 10.1056/NEJMoa053727, 7. 1. Gould Syndrome is an ultra rare genetic, multi-system disorder. Aicardi-Goutieres syndrome - About the Disease - Genetic and Rare Diseases Information Center National Center for Advancing Translational Sciences Browse by Disease About GARD Contact Us We recently launched the new GARD website and are still developing specific pages. (2013) 73:4857. 2012;54:569-574. https://www.ncbi.nlm.nih.gov/pubmed/22574627, Lanfranconi S, Markus HS. By continuing to use this website, you agree to the Terms of Service & Privacy Policy, A Podcast For The Rare Disease Community, Policy Statements & Letters to Policymakers. COL4A1 disorder is probably largely underestimated because of its multisystem and variable phenotype. COL4A1 encodes type IV collagen 1 chain, a crucial component of nearly all basement membrane including vasculature, renal glomerule and ocular structures. Novel heterozygous COL4A2 variant c.2572A>G, p.(I858V) mimicking Sneddon's and Divry van Bogaert Syndrome. Copyright 2023 NORD National Organization for Rare Disorders, Inc. All rights reserved. (2017) 377:111931. COL4A1/A2-related disorders are caused by dominant mutations in the COL4A1 or COL4A2 genes. Individuals with COL4A1/A2-related disorders have characteristic patterns of brain disease when viewed under advanced imaging techniques. In most people, small vessel disease in the brain does not cause symptoms. Resource(s) for Medical Professionals and Scientists on This Disease: J Genet Couns. Fazekas F, Chawluk JB, Alavi A. MR signal abnormalities at 1.5 T in Alzheimer's dementia and normal aging. eCollection 2022. One patient (IV-3) was treated for spasticity and seizures with valproic acid. One year later, right hemiparesis became clinically evident with a lack of right voluntary hand prehension in association with right hemineglect. Gunda B, Mine M, Kovcs T, Hornyk C, Bereczki D, Vrallyay G, Rudas G, Audrezet MP, Tournier-Lasserve E. J Neurol. Danbury, CT 06810 11:827. doi: 10.3389/fneur.2020.00827. Graefe's Arch Clin Exp Ophthalmol. Figure 3. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site. NORD gratefully acknowledges Douglas Gould, PhD, Professor, Director of Research, Denise B. Evans Endowed Chair in Ophthalmology, Departments of Ophthalmology and Anatomy, Institute for Human Genetics, University of California San Francisco School of Medicine, and the COL4A1 Foundation, for assistance in the preparation of this report. How can gene variants affect health and development? Autosomal Dominant Brain Small Vessel Disease. Phone: 617-249-7300, Danbury, CT office 2012;21:R97-R110. The COL4A1 and COL4A2 genes were screened in proband IV-6. The variant was confirmed by bidirectional fluorescence DNA sequencing (Sanger method). Gould Syndrome is an ultra rare genetic, multi-system disorder. I dont think we will ever be able to truly articulate our appreciation for Dr. Madsen and Boston Childrens for all that they did for Zeeva and our family. Genotype-phenotype correlations in pathology caused by collagen type IV alpha 1 and 2 mutations. Mutations in the COL4A1 gene cause HANAC syndrome. 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. 1A-B). (2014) 252:178994. Muscle cramps can be spontaneous or triggered by exercise. Acute urinary retention due to a novel collagen COL4A1 mutation. Individuals with HANAC syndrome also experience a variety of eye problems. Clinically, COL4A1 mutations are responsible for different overlapping phenotypes including porencephaly (24), brain small vessel disease (2, 57) with or without ocular anomalies, HANAC (13) (hereditary angiopathy with nephropathy, aneurysms, and muscle cramps) syndrome, ophthalmological abnormalities (912), and non-syndromic autosomal dominant congenital cataracts (10). COL4A1 -related brain small-vessel disease is characterized by weakening of the blood vessels in the brain. 2022 Mar 24;3:100140. doi: 10.1016/j.cccb.2022.100140. Deml B, Reis LM, Maheshwari M, Griffis C, Bick D, Semina E. Whole exome analysis identifies dominant COL4A1 mutations in patients with complex ocular phenotypes involving microphthalmia. We connect and coordinate our families with researchers and medical professionals to get our disease and management coordination into the medical realm. COL4A1 and COL4A2 are on Chr. Oct;152A(10):2550-5. doi: 10.1002/ajmg.a.33659. Phenotypic spectrum of COL4A1 mutations: porencephaly to schizencephaly. Here we report a family in which three siblings presented severe hypermetropia and porencephaly. Standardized human pedigree nomenclature: update and assessment of the recommendations of the National Society of Genetic Counselors. COL4A1/COL4A2 gene mutations description, symptoms and the sub-diagnosis. The main symptom is single or repeated bleeding inside the skull (intracranial hemorrhaging) that can occur without cause (spontaneously), after trauma, or when taking drugs that slow blood clotting (anticoagulants). NORD is a registered 501(c)(3) charity organization. He would separate the two halves of her brain by Years published: 2019. Other patients have been reported with cysts on the liver, irregular heartbeats (supraventricular arrhythmia), and Raynaud phenomenon, which is in which the fingers or toes become numb or have a prickly sensation in response to cold due to narrowing of blood vessels. The COL4A1 gene has 52 exons and most of the pathogenic variants are distributed across exons 10 to 47 in the triple-helix domain. She was struggling to advance both cognitively and physically because of uncontrolled epilepsy. ACS Omega. Cerebrovascular disease related to COL4A1 mutations in HANAC syndrome. COL4A1 mutations are responsible for a wide range of abnormalities affecting mainly the brain and the retinal vasculature, the anterior and posterior ocular structures and the renal glomerules. (2008) 17:42433. National Taiwan University Hospital, Taiwan, Kaohsiung Chang Gung Memorial Hospital, Taiwan, Carrera de Medicina, Universidad Cientfica del Sur, Peru, Federal University of Rio Grande do Sul, Brazil. 1900 Crown Colony Drive Please enable it to take advantage of the complete set of features! Endovascular therapy is a minimally-invasive procedure in which a long, thin tube called a catheter is passed into the blood vessel to repair or strengthen the blood vessel. Zagaglia S, Selch C, Nisevic JR, Mei D, Michalak Z, Hernandez-Hernandez L, et al. Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, et al. Axenfeld-Rieger anomaly is associated with various other eye abnormalities, including underdevelopment and eventual tearing of the colored part of the eye (iris), and a pupil that is not in the center of the eye. Fax: 203-263-9938, Washington, DC Office Neurology. 2010 Aug;41(8):e513-8. For example, the position of the mutation along the length of the protein can influence the severity of cerebrovascular disease and mutations in functional subdomains can influence the likelihood of tissue-specific involvement (for example, muscle). National Center for Biotechnology Information. Collagen alpha-1(IV) chain (COL4A1) is a protein that in humans is encoded by the COL4A1 gene on chromosome 13. COL4A1 codes for extracellular matrix proteins that form heterotrimers that are major components of nearly all organ basal membranes. doi: 10.1001/archophthalmol.2010.42, 10. When this enzyme is elevated, it is a sign of muscle damage. doi: 10.1212/01.WNL.0000123113.46672.68, 25. No ophthalmological surgery was planned on annual control for any member, but only positive lens correction prescribed. doi: 10.2214/ajr.149.2.351, 19. Painful muscle cramps can occur and can develop before three years of age. Ann Neurol. These genes are the blueprints for two proteins that wind together like a long rope inside cells. No microbleeds or cystic cavities were found. What are the different ways a genetic condition can be inherited? COL4A1 brain small-vessel disease is an autosomal dominant condition resulting from a mutation to the COL4A1 gene, located on the long arm of chromosome 13, that normally encodes for the alpha-1 chain of type IV collagen 1-6. government site. 10.2174/092986710790936293. Other eye problems experienced by people with COL4A1-related brain small-vessel disease include clouding of the lens of the eye (cataract) and the presence of arteries that twist and turn abnormally within the light-sensitive tissue at the back of the eye (arterial retinal tortuosity). Ronco P. Cerebrovascular disease related to COL4A1 mutations in HANAC syndrome. When our 8-year-old daughter, Zeeva, giggles and runs in her walker to the swing set, its like watching pure childhood joy. The latest research shows that insufficient COL4A1/A2 in basement membranes damages different tissues in very different ways. 2007 Aug;62(2):177-84. doi: 10.1002/ana.21191. Stroke is a leading cause of death and serious long-term disability in developed nations. Lanfranconi S, Markus HS. doi: 10.1111/j.1469-8749.2011.04198.x, 26. PMC (2014) 11:3612. It is possible that insufficient collagen in the basement membrane predisposes blood vessels in the brain to leak or rupture. These protein networks are the main components of basement membranes, which are thin sheet-like structures that separate and support cells in many tissues. The expressivity of the disease is highly variable with high intra- and inter-familial variability (2).