col4a1 syndrome life expectancycol4a1 syndrome life expectancy

doi: 10.1212/WNL.0000000000006567, PubMed Abstract | CrossRef Full Text | Google Scholar, 2. Illumina's Sequencing by Synthesis (SBS) technology (MiSeq Personal Sequencer, Illumina) analyzed the generated amplicons. We provide education, advocacy, and resources for families and individuals affected. Sibon I, Coupry I, Menegon P, Bouchet JP, Gorry P, Burgelin I, Calvas P, Lanfranconi S, Markus HS. MeSH The X and Y chromosomes are called the sex chromosomes and the rest all are called 'autosomes'. People listened to us and to Zeeva in a very different and proactive way. Zagaglia Selch C, Nisevic JR, et al. Gould Syndrome is a rare, genetic, multi-system disorder. Congenital Cephalic Disorders doi: 10.1111/j.1469-8749.2011.04198.x, 26. Individuals with COL4A1/A2-related disorders have characteristic patterns of brain disease when viewed under advanced imaging techniques. 2011 [Hereditary angiopathy with nephropathy, aneurysms and muscle cramps (HANAC): a new basement membrane-disease associated with mutations of the COL4A1 gene]. https://nord1dev.wpengine.com/for-patients-and-families/information-resources/info-clinical-trials-and-research-studies/, For information about clinical trials sponsored by private sources, contact: N Engl J Med. One year later, right hemiparesis became clinically evident with a lack of right voluntary hand prehension in association with right hemineglect. Some may only develop specific symptoms such as isolated migraines or strokes in childhood or adulthood. We therefore began our analysis of mutant Col4a1 G498V mice by examining the retinal vascular network at three and nine months of age. It is passed through families in a autosomal dominant fashion. This report highlights both the broad spectrum of COL4A1 mutations and the yield of testing the COL4A1 gene in familial ophthalmological and brain disorders. More info about Gould Syndrome is available at https://rarediseases.org/rare-diseases/col4a1-a2-related-disorders/. 11:827. doi: 10.3389/fneur.2020.00827. 2013;73:48-57. https://www.ncbi.nlm.nih.gov/pubmed/23225343, Kuo DS, Labelle-Dumais C, Gould DB. Last updated: Additional features 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. COL4A1-related brain small-vessel disease is characterized by weakening of the blood vessels in the brain. This site needs JavaScript to work properly. Genotype-phenotype correlations in pathology caused by collagen type IV alpha 1 and 2 mutations. Mice with Col4a1 and Col4a2 gene mutations have pathology in many organs and the presence and severity of pathology in a given organ appears to depend on the location of the mutation, genetic context, and environmental interactions. These aneurysms have the potential to burst, causing bleeding within the brain (hemorrhagic stroke). Combinations of the in silico tool MutationTaster (21) and the Alamut software (ALAMUT package, http://www.interactivebiosoftware.com, France) predicted the variant to be pathogenic as it likely alters the protein structure/function due to a detrimental effect on 112 heterotrimers formation and type IV collagen stability. 10.1161/STROKEAHA.110.581918. Cataracts, which are a clouding of the lenses of the eyes, are often present from birth (congenital) and may be one of the first identifiable signs of the syndrome. No patient had cramps, cardiac symptoms, or abnormalities or Raynaud phenomenon. Neurology. Resource(s) for Medical Professionals and Scientists on This Disease: The COL4A1 stroke syndrome. If the mutation arises after fertilization, then some cells will carry the mutation and others will not this is called mosaicism. A diagnosis of COL4A1/A2-related disorders is based upon identification of characteristic symptoms, a detailed patient and family history, a thorough clinical evaluation and a variety of specialized tests including advanced imaging techniques. Born at term after a 39-week pregnancy, IV-3 had an unremarkable first clinical evaluation at 3 months. Childhood presentation of COL4A1 mutations. 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. ), A variety of rare genetic disorders may have symptoms similar to those found in COL4A1/A2-related disorders. If neither parent carries the mutation, it is considered de novo which means that the mutation is a new occurrence. 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 the structure of the brain (cerebral cortical abnormalities) and lung (pulmonary) abnormalities continue to emerge and the full spectrum is still uncharacterized. doi: 10.1212/WNL.0000000000000837, 20. Please note that NORD provides this information for the benefit of the rare disease community. Mutations in COL4A1 or COL4A2 cause Gould Syndrome and, because these two proteins are found in almost all tissues; nearly any organ can be affected. Orignac I, Dousset V, Lacombe D, Orgogozo JM, Arveiler B, Goizet C. COL4A1 Suite 310 doi: 10.1001/archneur.1983.04050080067013, 17. Clipboard, Search History, and several other advanced features are temporarily unavailable. How are genetic conditions treated or managed? Ultrasound in utero from IV-6 (A). (2015) 88:46873. In the human genome, there are 46 chromosomes. The information on this site should not be used as a substitute for professional medical care or advice. 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. 2017 Jan;66:100-103. doi: 10.1016/j.pediatrneurol.2016.04.010. The retina is the light-sensitive membrane that lines the inside of the eyes. Years published: 2019. Your support helps to ensure everyones free access to NORDs rare disease reports. Summary. It affects mainly young adults, children and more typically neonates. This analysis represents a subanalysis of the 35 out of 60 children <=18 years of age who reported a history of seizures. Compared to other COL4A1-related disorders, the brain is only mildly affected in HANAC syndrome. Email: [emailprotected], Some current clinical trials also are posted on the following page on the NORD website: Copyright 2023 by Gould Syndrome Foundation -. Washington, DC 20036 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. There are no standardized treatment protocols or guidelines for affected individuals. mutation in Axenfeld-Rieger anomaly with leukoencephalopathy and stroke. BMC Med Genet. doi: 10.1016/j.ejpn.2009.04.010, 27. The COL4A2 test was negative. The extents to which intracellular and/or extracellular insults contribute to pathology remain an open question. The causative gene of HANAC is COL4A1 (13q34) encoding the alpha1 chain of collagen IV, a major component of basement membranes also involved in . Axenfeld-Rieger anomaly and cataract can cause impaired vision. Full ophthalmological evaluations including slit lamp and fundoscopy were realized and disclosed for bilateral hypermetropia in IV-3 [15 dioptre (D)], IV-6 (8.5 D), IV-5 (10 D), and III-3 (7 D). https://www.ncbi.nlm.nih.gov/pubmed/20558831, Alamowitch S, Plaisier E, Favrole P, et al. (2017) 377:111931. COL4A1 encodes type IV collagen 1 chain, a crucial component of nearly all basement membrane including vasculature, renal glomerule and ocular structures. Gould Syndrome is an ultra rare genetic, multi-system disorder. 2012;21:R97-R110. Recent findings: FOIA PS and NL: followed III-3 at the Erasme Neurology outpatients clinic. These disorders include autosomal dominant retinal vasculopathy with cerebral leukodystrophy (RVCL), hereditary endotheliopathy with retinopathy, nephropathy, and stroke (HERNS), cerebral autosomal recessive arteriopathy with subcortical infarcts and leukodystrophy (CARASIL), mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), Fabry disease, and a variety of leukodystrophies, rare progressive metabolic disorders that affect the brain, spinal cord and often the peripheral nerves. Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/. 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. Some individuals do not have any observable symptoms (asymptomatic); others can develop severe, even life-threatening complications. This review dsecribes the clinical spectrum of a newly identified disorder related to COL4A1 gene mutations. COL4A1/COL4A2 gene mutations description, symptoms and the sub-diagnosis. The expanding phenotype of COL4A1 and COL4A2 mutations: clinical data on 13 newly identified families and review of the literature. When we didnt feel we had any options left for treatment, doi: 10.1007/s00417-014-2800-6, 12. 2022 Mar 24;3:100140. doi: 10.1016/j.cccb.2022.100140. To date, over 50 pathogenic or likely pathogenic variants have been described in the COL4A1 gene, most of them missense (2). Feb;24(1):63-8. doi: 10.1097/WCO.0b013e32834232c6. mutations: a novel genetic multisystem disease. Stroke subtype, vascular risk factors, and total MRI brain small-vessel disease burden. for the triple helical CB3[IV] domain. doi: 10.1038/gim.2015.30, 21. doi: 10.1016/j.matbio.2016.10.003, 23. 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. Meuwissen MEC, Halley DJJ, Smit LS, Lequin MH, Cobben JM, De Coo R, et al. 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 . Most individuals diagnosed with a COL4A1-related disorder have an affected parent. Cerebral small vessel disease with hemorrhage is likely milder continuum from porencephaly and exhibits many of the same symptoms (with the exception of the brain cavities). After a normal neonatal period, those affected develop a rapidly progressive course involving irritability, hyperaesthesia, visual and hearing loss, severe cognitive and motor deterioration, and seizures. NORD is a registered 501(c)(3) charity organization. Seattle, WA: University of Washington, Seattle; 1993-. We describe, here, the phenotype of a likely pathologic variant (p.Gly743Val) in exon 30 of the COL4A1 gene, responsible for an oculo-cerebral phenotype characterized by severe hypermetropia and highly penetrant porencephaly in absence of other systemic complications. Suite 500 (2004) 62:16135. J Med Genet. Figure 3. Clin Neurol Neurosurg. 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. ClinVar; [VCV000389182.3]. Neuropsychological tests disclosed language delay and learning difficulties requiring speech therapy at the age of 9 years. Clin Genet. doi: 10.1038/gim.2014.210, 3. Muscle cramps can be spontaneous or triggered by exercise. Fetal intracerebral hemorrhage and cataract: think COL4A1. IV-5Brain MRI revealing porencephalic cyst of frontal horn of lateral right ventricle (C). This condition causes mutations in genes that produce a specific type of collagen. Neurovascular Alterations in Vascular Dementia: Emphasis on Risk Factors. Various treatments have been reported in the medical literature as part of single case reports or small series of patients. 4 Both . Quincy, MA 02169 Cavalin M, Mine M, Philbert M, et al. INTERNET Therefore, it is important to note that there is a very broad spectrum of clinical presentations with different organs affected to different degrees between 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. Xia XY, Li N, Cao X, Wu QY, Li TF, Zhang C, et al. NORD and MedicAlert Foundation have teamed up on a new program to provide protection to rare disease patients in emergency situations. While muscle cramps may begin in childhood, many of the other symptoms do not appear until later in life. The COL4A1 gene mutations that cause HANAC syndrome result in the production of a protein that disrupts the structure of type IV collagen. 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. The number of genes implicated in epilepsy has grown rapidly in the past decade. Powered by NORD, the IAMRARE Registry Platform is driving transformative change in the study of rare disease. Matrix Biol. U.S. Department of Health and Human Services, Autosomal dominant familial hematuria, retinal arteriolar tortuosity, contractures, Hereditary angiopathy with nephropathy, aneurysm, and muscle cramps syndrome. the basement membranes surrounding the body's blood vessels, National Organization for Rare Disorders (NORD), BRAIN SMALL VESSEL DISEASE 1 WITH OR WITHOUT OCULAR ANOMALIES. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Disclaimer. Hereditary cerebral small vessel diseases: a review. Mutations in COL4A3, COL4A4 and COL4A5 were found in the early 1990's in patients with Alport Syndrome. 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. The heterozygous variant c.2228G>T [NM_001845.4(COL4A1):c.2228G>T (p.Gly743Val)] was identified in exon 30 of the COL4A1 gene. See our, Hereditary angiopathy with nephropathy, aneurysms, and muscle cramps syndrome, URL of this page: https://medlineplus.gov/genetics/condition/hereditary-angiopathy-with-nephropathy-aneurysms-and-muscle-cramps-syndrome/. COL4A1-related brain small-vessel disease is part of a group of conditions called the COL4A1-related disorders. Stroke. The effects of the disorder range from subtle or mild to severe, depending on associated brain abnormalities. When these ropes are secreted, they assemble into net-like structures outside the cells. 2018;91:e2078-e2088. National Library of Medicine J Neurol Sci. Pediatr Neurol. Surgery or endovascular therapy can be used to treat intracranial hemorrhage. 2012;322:25-30. https://www.ncbi.nlm.nih.gov/pubmed/22868088, Shah S, Ellard S, Kneen R, et al. 1900 Crown Colony Drive Standardized (15) familiar pedigree is showed in Figure 1. seizure activity. Arterial retinal tortuosity can cause episodes of bleeding within the eye following any minor trauma to the eye, leading to temporary vision loss. basement membranes surrounding the body's blood vessels, Genetic Testing Registry: Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps, National Organization for Rare Disorders (NORD), ANGIOPATHY, HEREDITARY, WITH NEPHROPATHY, ANEURYSMS, AND MUSCLE CRAMPS. But she is learning to read, enjoys swimming, horseback riding, and is a glass jewelry and pottery artist. doi: 10.1212/WNL.0000000000001309, 8. (2011) 42:13. COL4A1 may be a candidate gene in unexplained familial syndromes with autosomal dominant hematuria, cystic kidney disease, intracranial aneurysms, and muscle cramps. Copyright 2020 Scoppettuolo, Ligot, Wermenbol, Van Bogaert and Naeije. Doctors and researchers to bring research and medical therapeutic options to those affected. Sci Rep. 2016;6:18602. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728690/, Rannikmae K, Davies G, Thomson PA, et al. Staals J, Makin SDJ, Doubal FN, Dennis MS, Wardlaw JM. 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. A Podcast For The Rare Disease Community, Policy Statements & Letters to Policymakers. Vahedi K, Alamowitch S. Clinical spectrum of type IV collagen (COL4A1) She, then, developed seizures which were controlled by valproic acid. 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 Other eye problems associated with HANAC syndrome include a clouding of the lens of the eye (cataract) and an abnormality called Axenfeld-Rieger anomaly. Mosaicism can contribute to both reduced penetrance or variable expressivity but other factors do as well. What does it mean to have a COL4A1 gene mutation: The COL4A1 gene provides instructions for making one component of type IV collagen, which is a flexible protein important in the structure of many. Muscle cramps experienced by most people with HANAC syndrome typically begin in early childhood. Other phenotypes include intracranial aneurysms, porencephaly, infantile hemiparesis, muscle cramps, optic nerve dysgenesis and secondary glaucoma. 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.) 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. Individuals with COL4A1 or COL4A2 mutations can also develop formation of clefts or slits in the two halves of the brain (schizencephaly) in which cerebral hemispheres are missing and replaced with sacs filled with cerebrospinal fluid (hydranencephaly), abnormal folds in the brain surface (polymicrogyria) or abnormalities in the normal laying of the neuronal cells in the brain (cortical lamination defects). Neurology. Some of these patients have been described as having HANAC syndrome, which is an acronym for hereditary angiopathy, nephropathy, aneurysms, and muscle cramps. my mom suggested we call Boston Childrens Hospital. When an individual tests positive for a mutation but does not manifest the effects, it is referred to as having incomplete or reduced penetrance.

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