col4a1 syndrome life expectancy

We described the phenotype associated to a likely pathogenic variant of the COL4A1 gene (c.2228G>T, p.Gly743Val) responsible for severe hypermetropia and familial porencephaly. Hereditary angiopathy with nephropathy, aneurysms, and muscle cramps (HANAC) syndrome is part of a group of conditions called the COL4A1-related disorders. 1900 Crown Colony Drive Neurol. 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. The variant was confirmed by bidirectional fluorescence DNA sequencing (Sanger method). Stroke is a leading cause of death and serious long-term disability in developed nations. Phone: 202-588-5700. 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). When these ropes are secreted, they assemble into net-like structures outside the cells. Gould Syndrome Foundation (COL4a1/COL4A2) seeks to educate the community on the rare disease COL4A1 and it's subcategorical diagnosis'. 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. In cases where the mutation is inherited, the carrier parent is often clinically unaffected. Novel heterozygous COL4A2 variant c.2572A>G, p.(I858V) mimicking Sneddon's and Divry van Bogaert Syndrome. 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. Brain magnetic resonance imaging (MRI) scans were carried out on a three Tesla Brain MRI (Achieva, Ingenia; Philips Healthcare, Best, The Netherlands). COL4A1/A2-related disorders are believed to affect females and males in equal numbers. Feb;24(1):63-8. doi: 10.1097/WCO.0b013e32834232c6. Other causes of porencephaly were ruled out [maternal alloimmunization, trauma, peri-natal cerebral ischemia (normal Apgar scores at birth), and negative TORCH complex tests]. Here, we report a patient with schizencephaly, detected by fetal ultrasonography and fetal magnetic resonance imaging, with a de novo novel mutation in COL4A1 (c.2645_2646delinsAA, p.Gly882Glu). National Institute of Neurological Disorders and Stroke. 11:827. doi: 10.3389/fneur.2020.00827. Phone: 617-249-7300, Danbury, CT office Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology Sue. Berg R, Aleck A, Kaplan A. Familial porencephaly. 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, . Jeanne M, Gould DB. Graefe's Arch Clin Exp Ophthalmol. The site is secure. 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). These genes are the blueprints for two proteins that wind together like a long rope inside cells. Rarely, new mutations in the gene occur in people with no history of the disorder in their family. The brain MRI of IV-6 disclosed a large right-sided frontoparietal cavity (Figure 3B) with communication to the lateral ventricle, isosignal to CFS. Plaisier E, Chen Z, Gekeler F, Benhassine S, Dahan K, Marro B, Alamowitch S, Paques M, Ronco P. Am J Med Genet A. BMC Med Genet. 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). NORD is a registered 501(c)(3) charity organization. ClinVar; [VCV000389182.3]. https://www.ncbi.nlm.nih.gov/pubmed/26610912. We connect and coordinate our families with researchers and medical professionals to get our disease and management coordination into the medical realm. PMC COL4A1 Syndrome CADASIL This group rarely survives beyond 2 years. Interpretation of variant significance was done according to the American College of Medical Genetics and Genomics (ACMG) standards and guidelines (20). Quincy, MA 02169 1779 Massachusetts Avenue She was struggling to advance both cognitively and physically because of uncontrolled epilepsy. Treatment trials will be critical to determine the long-term safety and effectiveness of specific medications and treatments for individuals with COL4A1/A2-related disorders. Vahedi K, Alamowitch S. Clinical spectrum of type IV collagen (COL4A1) At 2 years old, IV-6 presented obvious left hemiparesis but could move without help. Am J Neuroradiol. Hereditary cerebral small vessel diseases: a review. In most cases, an affected person has one parent with the condition. and transmitted securely. Exome sequencing in 32 patients with anophthalmia/microphthalmia and developmental eye defects. The expanding phenotype of COL4A1 and COL4A2 mutations: clinical data on 13 newly identified families and review of the literature. HANAC syndrome is characterized by angiopathy, which is a disorder of the blood vessels. 2022 May 27;13:827165. doi: 10.3389/fneur.2022.827165. In the human genome, there are 46 chromosomes. In addition the whole spectrum of the phenotype is not yet known and there are many asymptomatic patients. Common variation in COL4A1/COL4A2 is associated with sporadic cerebral small vessel disease. 2008 May;192(5):971-84; discussion 984-6. When an individual tests positive for a mutation but does not manifest the effects, it is referred to as having incomplete or reduced penetrance. Gould Syndrome is diagnosed following a genetic test revealing a mutation in COL4A1 or COL4A2. Genet Med. Seattle, WA: University of Washington, Seattle; 1993-. People with HANAC syndrome develop kidney disease (nephropathy). Gould Syndrome is a rare, genetic, multi-system disorder. COL4A1/A2-related disorders follow an autosomal dominant pattern of inheritance. CADASIL is an acronym that stands for: (C)erebral relating to the brain (A)utosomal (D)ominant a form of inheritance in which one copy of an abnormal gene is necessary for the development of a disorder (A)rteriopathy disease of the arteries (blood vessels that carry blood away from the heart) (S)ubcortical relating to specific areas of the brain supplied by deep small arteries (I)nfarcts tissue loss in the brain caused by lack of blood flow to the brain, which occurs when circulation through the small arteries is severely reduced or interrupted (L)eukoencephalopathy lesions in the brain white matter caused by the disease and observed on MRI. 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. doi: 10.1001/archophthalmol.2010.42, 10. IV-6 was born at 35 weeks after a pregnancy marked by gestational diabetes. Collagen, type IV, alpha 1 - Wikipedia Some of the patient advocacy organizations listed in the Resources section below provide support and information to affected individuals and their families. In affected individuals, stroke is usually caused by bleeding in the brain (hemorrhagic stroke) rather than a lack of blood flow in the brain (ischemic stroke), although either type can occur. COL4A1-related brain small-vessel disease is characterized by weakening of the blood vessels in the brain. Would you like email updates of new search results? Gould DB, Phalan FC, Breedveld GJ, Van Mil SE, Smith RS, Schimenti JC, et al. 2015;17:843-853. https://www.nature.com/articles/gim2014210, Yoneda Y, Haginoya K, Kato M, et al. 13 and so Gould Syndrome is considered Autosomal and should affect males and females in equal numbers. Childhood presentation of COL4A1 mutations. J Neurol Sci. Because the collagen is found throughout the body, COL4A1/A2 affects many organ systems, including the brain, kidneys, eyes, and muscles. doi: 10.2214/ajr.149.2.351, 19. Dr. Madsen suggested Zeeva have an operation called a Role of COL4A1 in basement-membrane integrity and cerebral small-vessel disease. Col4a1 mutation generates vascular abnormalities correlated with 2012;21:R97-R110. The COL4A2 test was negative. There are notable differences in the specific signs and symptoms (clinical heterogeneity), and different organs are affected to different degrees between patients even among members of a family who carry the same gene mutation. Only one copy of COL4A1 or COL4A2 needs to acquire a mutation in order to cause disease which means the mutations are Dominant thus, Gould Syndrome is considered Autosomal Dominant. An MRI uses a magnetic field and radio waves to produce cross-sectional images of particular organs and bodily tissues, including the brain. Epub 2016 Apr 24. 128:4839. Fetal origin of brain damage in 2 infants with a COL4A1 mutation: fetal and neonatal MRI. Sci Rep. 2016;6:18602. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728690/, Rannikmae K, Davies G, Thomson PA, et al. 2009 Jun 25 [Updated 2016 Jul 7]. All patients suffering from HANAC syndrome display retinal arteriolar tortuosity and occasional retinal hemorrhages. Dev Med Child Neurol. IV-3 goes to a normal school, but special schooling is required for IV-6. Mutations in Col4a1 cause perinatal cerebral hemorrhage and porencephaly. Phone: 203-263-9938 Fazekas F, Chawluk JB, Alavi A. MR signal abnormalities at 1.5 T in Alzheimer's dementia and normal aging. 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.) COL4A1 -related brain small-vessel disease is characterized by weakening of the blood vessels in the brain. Born at term after a 39-week pregnancy, IV-3 had an unremarkable first clinical evaluation at 3 months. Nat Methods. Unable to load your collection due to an error, Unable to load your delegates due to an error. To use the sharing features on this page, please enable JavaScript. Autosomal Dominant Familial Porencephaly Type I. The X and Y chromosomes are called the sex chromosomes and the rest all are called 'autosomes'. Neurology. COL4A1 mutations cause progressive retinal neovascular defects and retinopathy. The causative gene of HANAC is COL4A1 (13q34) encoding the alpha1 chain of collagen IV, a major component of basement membranes also involved in . Urine analysis to test for blood or excess protein can be used to evaluate renal function and identify if the kidneys might be affected. Suite 500 1779 Massachusetts Avenue Zagaglia Selch C, Nisevic JR, et al. One patient (IV-3) was treated for spasticity and seizures with valproic acid. Ann Neurol. Next generation sequencing uncovers a missense mutation in COL4A1 as the cause of familial retinal arteriolar tortuosity. The surgery We each inherit a full complement on autosomes from each of our parents giving us two copies of each gene. Each child of an individual with a COL4A1-related disorder has a 50% chance of inheriting the pathogenic variant. 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. doi: 10.1186/s12881-014-0097-2, 11. Neurology. 1900 Crown Colony Drive COL4A2 mutation causing adult onset recurrent intracerebral hemorrhage and leukoencephalopathy. 1 Survivors often have a severely diminished quality of life, require long-term care, and are at high risk . Genotype-phenotype correlations in pathology caused by collagen type IV alpha 1 and 2 mutations. Danbury, CT 06810 Hereditary angiopathy with nephropathy, aneurysms, and - MedlinePlus 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). The first reports of human COL4A1 mutations were in patients with autosomal dominant porencephaly and a more recent study found that COL4A1 mutations were found in ~16% of patients with porencephaly. Neuropsychological tests disclosed language delay and learning difficulties requiring speech therapy at the age of 9 years. Colin E, Sentilhes L, Sarfati A, Mine M, Guichet A, Ploton C, et al. Changing lives of those with rare disease. 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. 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. Here we report a family in which three siblings presented severe hypermetropia and porencephaly. 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). These protein networks are the main components of basement membranes, which are thin sheet-like structures that separate and support cells in many tissues. A Podcast For The Rare Disease Community, Policy Statements & Letters to Policymakers. 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. Developmental defects to the front of the eye, which also includes the ocular drainage structures between the iris and cornea, can lead to increased pressure in the eye (elevated intraocular pressure, or IOP). eCollection 2021. Curr Opin Neurol. There is in addition a specific phenotype called HANAC with constant nephropathy, muscle cramps and frequent intracranial aneurysms. PS: wrote thi paper and performed the review of the literature under the supervision of GN. All authors contributed to the article and approved the submitted version. Epub 2022 Apr 14. Type IV Collagens and Basement Membrane Diseases: Cell Biology and Pathogenic Mechanisms. Six alpha chains of type IV. (2015) 17:84353. The non-working gene can be inherited from either parent or can be the result of a mutated (changed) gene in the affected individual (called sporadic or de novo). Cavalin M, Mine M, Philbert M, et al. To use the sharing features on this page, please enable JavaScript. Paques M, Ronco P. Novel COL4A1 mutations associated with HANAC syndrome: a role 10.2174/092986710790936293. Suite 500 (2006) 354:148996. Phone: 617-249-7300, Danbury, CT office Due to the rarity of the disease, there are no treatment trials that have been tested on a large group of patients. This can lead to problems 1) if too much of the misfolded protein accumulates within cells, 2) if not enough of the protein exits the cells to form networks, and 3) occasionally, the presence of the mutant proteins outside the cells can interfere with the structure of the network. Mutations in the gene have been linked to diseases of the brain, muscle, kidney, eye, and cardiovascular system.

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