Molecular analysis in the father disclosed a heterozygous variant c.2228G>T (p.Gly743Val) in exon 30 of the COL4A1 gene that segregated with the phenotype. The COL4A1 gene provides instructions for making one component of a protein called type IV collagen. Various muscles can be affected and muscle strength can become weakened. Epub 2010 Jun 17. However, in people with HANAC syndrome, these aneurysms typically do not burst. 10.2174/092986710790936293. 2011 doi: 10.1212/WNL.0b013e3181eee440, 28. Early intervention is important in ensuring that children with reach their highest potential. Epub 2016 Apr 24. He smiled, caught it, and asked Zeeva if he could throw it back. Danbury, CT 06810 Our data testing the effects of established mutations on collagen biosynthesis suggest that the intracellular retention of mutant COL4A1 proteins at the expense of their secretion appears to be a common effect of many COL4A1 mutations. Cerebrovascular disease related to COL4A1 mutations in HANAC syndrome. The disorder causes many symptoms, not the least of which are strokes and epilepsy. 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. Cerebrovascular disease related to COL4A1 mutations in HANAC syndrome. When this enzyme is elevated, it is a sign of muscle damage. ClinVar; [VCV000389182.3]. Genotype-phenotype correlations in pathology caused by collagen type IV alpha 1 and 2 mutations. Glaucoma is initially treated with topical medications and, if medical therapy is unsuccessful, surgery. Bethesda, MD 20894, Web Policies 2021 Sep 10;13:727590. doi: 10.3389/fnagi.2021.727590. Several factors including the small number of identified cases, the lack of large clinical studies, and the possibility of other genes or factors influencing the disorder make it challenging to develop a complete picture of associated symptoms and prognosis. doi: 10.2214/ajr.149.2.351, 19. 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. A novel COL4A1 gene mutation results in autosomal dominant non-syndromic congenital cataract in a Chinese family. An official website of the United States government. These types of correlations can be difficult to detect in patients because of the broad genetic variability in humans. Washington, DC 20036 The size and location of cerebral cavities contributes to clinical variability. In most people, small vessel disease in the brain does not cause symptoms. The strengths of our study are the extensive systemic work-up, the 5-year neurological follow-up, and the pluridisciplinary approach. Genetic counseling will be proposed when IV-3 and IV-6 intend to start a family as there is a 50% risk of mutation transmission to the next generation and potential obstetrical complications. Type IV collagen molecules attach to each other to form complex protein networks. We are a registered 501(c)3 Nonprofit dedicated to providing hope and help to children and adults with Gould Syndrome; affecting COL4A1 and COL4A2 genes. Orignac I, Dousset V, Lacombe D, Orgogozo JM, Arveiler B, Goizet C. COL4A1 Congenital Cephalic Disorders Nat Methods. Exon mutations of the COL4A1 genes are responsible for a broad spectrum of cerebral, ocular, and systemic manifestations. GeneReviews. NORD is not a medical provider or health care facility and thus can neither diagnose any disease or disorder nor endorse or recommend any specific medical treatments. Resource(s) for Medical Professionals and Scientists on This Disease: Lanfranconi S, Markus HS. Mosaic individuals are likely less severely affected, or even asymptomatic, because they have many cells that secrete COL4A1 normally and that can compensate for those cells that cannot. Compared to other COL4A1-related disorders, the brain is only mildly affected in HANAC syndrome. Changing lives of those with rare disease. Neurol. This raises questions about what tests Liliane has a lot to be grateful for this holiday season. IV-3 was diagnosed with ventriculomegaly in utero. Gould DB, Phalan FC, Breedveld GJ, Van Mil SE, Smith RS, Schimenti JC, et al. Participants with epilepsy frequently reported developmental delays (88.6%), stroke (60.0%), cerebral palsy (65.7%), and constipation (57.1%). The cells of the retina trigger nerve impulses that run from the optic nerve to the brain to form sight. Contact a health care provider if you have questions about your health. For example, an individual may carry genetic variants elsewhere in their genome that confers protection or susceptibly to the mutation and environmental experiences (trauma, anticoagulant use, physical exertion etc.) However, there are exceptions that depend on precisely when and where the mutation arose. Systemic work-up including renal function, CK levels, urinary sediment test, and renal ultrasound proved unremarkable. This site needs JavaScript to work properly. The effects of the disorder range from subtle or mild to severe, depending on associated brain abnormalities. Gunda B, Mine M, Kovcs T, Hornyk C, Bereczki D, Vrallyay G, Rudas G, Audrezet MP, Tournier-Lasserve E. J Neurol. Bookshelf (1982) 40:5679. Novel heterozygous COL4A2 variant c.2572A>G, p.(I858V) mimicking Sneddon's and Divry van Bogaert Syndrome. 2010;41:e513-518. Six alpha chains of type IV. mutation in Axenfeld-Rieger anomaly with leukoencephalopathy and stroke. IV-5Brain MRI revealing porencephalic cyst of frontal horn of lateral right ventricle (C). The first time he came to meet us, Zeeva threw a sock at him. Pediatricians are physicians who specialize in the childhood disorders and are often the first to detect patients with COL4A1/A2-related disorders. The prevalence of HANAC syndrome (hereditary angiopathy-nephropathy-aneurysms-muscle cramps syndrome) is not available, but at least six affected families have been reported worldwide to date. If we dont have a program for you now, please continue to check back with us. Plaisier E, Chen Z, Gekeler F, Benhassine S, Dahan K, Marro B, Alamowitch S, Paques M, Ronco P. Am J Med Genet A. 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. Received: 06 January 2020; Accepted: 01 July 2020; Published: 11 September 2020. Ann Neurol. 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. During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of certain tissue structures. Some of the patient advocacy organizations listed in the Resources section below provide support and information to affected individuals and their families. Autosomal Dominant Brain Small Vessel Disease. Zenteno JC, Cresp J, Buentello-Volante B, Buil JA, Bassaganyas F, Vela-Segarra JI, et al. This group rarely survives beyond 2 years. Copyright 2023 by Gould Syndrome Foundation -. Because the collagen is found throughout the body, COL4A1/A2 affects many organ systems, including the brain, kidneys, eyes, and muscles. What is the prognosis of a genetic condition? This condition causes mutations in genes that produce a specific type of collagen. Dr. Joseph Madsen was as wonderful in person as he had been on the phone. COL4A1/A2-related disorders can also be associated with a variety of abnormalities affecting the front or back of the eyes. doi: 10.1136/jmg.2005.035584, 15. (2006) 354:148996. Please note that NORD provides this information for the benefit of the rare disease community. September 2003. Neurology. This review dsecribes the clinical spectrum of a newly identified disorder related to COL4A1 gene mutations. In: Adam MP, Everman DB, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. MedlinePlus links to health information from the National Institutes of Health and other federal government agencies. Many patients with COL4A1 and COL4A2 mutations have additional signs and symptoms that do not include the cerebral vasculature. To use the sharing features on this page, please enable JavaScript. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. 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). 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 NORDs mission. Gould DB, Phalan FC, van Mil SE, Sundberg JP, Vahedi K, Massin P, et al. 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. Cavalin M, Mine M, Philbert M, et al. Childhood presentation of COL4A1 mutations. By continuing to use this website, you agree to the Terms of Service & Privacy Policy. IV-6 was born at 35 weeks after a pregnancy marked by gestational diabetes. Collagen alpha-1(IV) chain (COL4A1) is a protein that in humans is encoded by the COL4A1 gene on chromosome 13. Neuropediatrics. Doctors and researchers to bring research and medical therapeutic options to those affected. Changing lives of those with rare disease. Various treatments have been reported in the medical literature as part of single case reports or small series of patients. Over 100 families have been identified with these disorders in the medical literature and many more cases are known that are not in the published literature. 2008 May;192(5):971-84; discussion 984-6. doi: 10.1111/j.1469-8749.2011.04198.x, 26. In the human genome, there are 46 chromosomes. Genotype-phenotype correlations in pathology caused by collagen type IV alpha 1 and 2 mutations. 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. 1A-B). cutting tissue called the corpus callosum, then make some additional delicate Individuals with this condition are at increased risk of having more than one stroke in their lifetime. Suite 310 for the triple helical CB3[IV] domain. mutations: a novel genetic multisystem disease. (2010) 14:1827. 55 Kenosia Avenue People listened to us and to Zeeva in a very different and proactive way. January 31, 2019 Going from having seizures every day for six years to having no seizures is nothing short of a miracle. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site. and transmitted securely. One patient (IV-3) was treated for spasticity and seizures with valproic acid. If either parent also carries the mutation, it is considered inherited. Stroke subtype, vascular risk factors, and total MRI brain small-vessel disease burden. Gould Syndrome Foundation (COL4a1/COL4A2) seeks to educate the community on the rare disease COL4A1 and it's subcategorical diagnosis'. Keywords: COL4A1, Type IV collagen, familial porencephaly, ocular malformations, variable expressivity, Citation: Scoppettuolo P, Ligot N, Wermenbol V, Van Bogaert P and Naeije G (2020) p.Gly743Val Mutation in COL4A1 Is Responsible for Familial Porencephaly and Severe Hypermetropia. Other causes of porencephaly were ruled out [maternal alloimmunization, trauma, peri-natal cerebral ischemia (normal Apgar scores at birth), and negative TORCH complex tests]. Phone: 617-249-7300, Danbury, CT office Here we report a family in which three siblings presented severe hypermetropia and porencephaly. COL4A1-related brain small-vessel disease is a rare condition, although the exact prevalence is unknown. In addition the whole spectrum of the phenotype is not yet known and there are many asymptomatic patients. Focke JK, Veltkamp R, Bauer P, Kraemer M. J Neurol. 30. Powered by NORD, the IAMRARE Registry Platform is driving transformative change in the study of rare disease. Axenfeld-Rieger is a collection of abnormalities affecting the front of the eye including the iris (colored part of the eye) and cornea (abnormally small corneas called microcornea), which is the transparent membrane that covers the eyes. As a result, type IV collagen molecules cannot attach to each other to form the protein networks in basement membranes.