col4a1 syndrome life expectancy col4a1 syndrome life expectancy

(For more information on this disorder, choose cadasil as your search term in the Rare Disease Database. This group rarely survives beyond 2 years. Type IV Collagens and Basement Membrane Diseases: Cell Biology and Pathogenic Mechanisms. 4 Both . 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. Danbury, CT 06810 Mutations in Col4a1 cause perinatal cerebral hemorrhage and 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, . 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. Autosomal Dominant Familial Porencephaly Type I. How are genetic conditions treated or managed? 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: Affected infants and children can exhibit delays in reaching developmental milestones and varying degrees of intellectual disability. Abnormal blood vessels in the brain are a major consequence of COL4A1 and COL4A2 gene mutations. We describe here the phenotype of a likely pathogenic gene variant, p.Gly743Val, which is responsible for a missense mutation in the COL4A1 gene exon 30 in a three generation family with severe hypermetropia and highly penetrant porencephaly in the absence of systemic manifestations. Gould Syndrome is diagnosed following a genetic test revealing a mutation in COL4A1 or COL4A2. Basement membranes without these networks are unstable, leading to weakening of the tissues that they surround. 2018;91:e2078-e2088. COL4A1 -related brain small-vessel disease is part of a group of conditions called the COL4A1 -related disorders. This raises questions about what tests Liliane has a lot to be grateful for this holiday season. The outcomes are highly variable ranging from brain hemorrhage before birth (in utero) leading to cavities in the brain (porencephaly) to mild age-related brain abnormalities that can only be observed on a specialized x-ray called magnetic resonance imaging (MRI). Recent findings: and transmitted securely. eCollection 2022. 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. National Library of Medicine Childhood presentation of COL4A1 mutations. Prenatal clinical manifestations in individuals with COL4A1/2 variants. doi: 10.1056/NEJMoa071906, 14. All individuals with this condition have arteries that twist and turn abnormally within the light-sensitive tissue at the back of the eyes (arterial retinal tortuosity). Dev Med Child Neurol. No ophthalmological surgery was planned on annual control for any member, but only positive lens correction prescribed. Neurol. The cells of the retina trigger nerve impulses that run from the optic nerve to the brain to form sight. 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 The COL4A1 gene mutations that cause HANAC syndrome result in the production of a protein that disrupts the structure of type IV collagen. (1987) 8:4216. Suite 310 Genet Med. However, in people with HANAC syndrome, these aneurysms typically do not burst. 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. small vessel disease: a systematic review. 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. 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. View CNBC interview with NORDs Peter Saltonstall and Boston Childrens Dr. Olaf Bodamer emphasizing the importance of investment in rare diseases. . 2021 Sep 10;13:727590. doi: 10.3389/fnagi.2021.727590. 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. Advanced imaging techniques can include computerized tomography (CT) scanning and magnetic resonance imaging (MRI). (2005) 308:116771. She had seizures every day, couldnt gain weight, sleep right, or generally enjoy her life. PS and NL: followed III-3 at the Erasme Neurology outpatients clinic. Sci Rep. 2016;6:18602. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728690/, Rannikmae K, Davies G, Thomson PA, et al. Curr Med Chem. Collagen type IV alpha 1 (COL4A1) and 2 (COL4A2) are extracellular matrix proteins that together constitute a major component of nearly all basement membranes. Rare disorders often go misdiagnosed or undiagnosed, making it difficult to determine their true frequency in the general population. Nearly half of these participants were diagnosed with infantile spasms. 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. 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). Rouaud T, Labauge P, Lasserve ET, Mine M, Coustans M, Deburghgraeve V, et al. Mosaicism can contribute to both reduced penetrance or variable expressivity but other factors do as well. Genotype-phenotype correlations in pathology caused by collagen type IV alpha 1 and 2 mutations. Cerebrovascular disease related to COL4A1 mutations in HANAC syndrome. Genet Med. 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. MedlinePlus links to health information from the National Institutes of Health and other federal government agencies. Xia XY, Li N, Cao X, Wu QY, Li TF, Zhang C, et al. Gunda B, Mine M, Kovcs T, Hornyk C, Bereczki D, Vrallyay G, Rudas G, Audrezet MP, Tournier-Lasserve E. J Neurol. The size and location of cerebral cavities contributes to clinical variability. COL4A1 is a subunit of the type IV collagen and plays a role in angiogenesis. Zeeva woke up after a ten-hour procedure, opened her eyes, and it felt like we were seeing her for the first time. Neurology. Neurology. Alamowitch S, Plaisier E, Favrole P, Prost C, Chen Z, Van Agtmael T, Marro B, MedlinePlus also links to health information from non-government Web sites. MeSH Mutations in the COL4A1 gene cause HANAC syndrome. Rarely, new mutations in the gene occur in people with no history of the disorder in their family. She, then, developed seizures which were controlled by valproic acid. The two genes that code for these proteins are tightly linked on chromosome 13 and dominant COL4A1 and COL4A2 gene mutations cause a highly variable, multisystem disorder. Written informed consent was obtained from the patient and the patient's parents for publication of this case report. More info about Gould Syndrome is available at https://rarediseases.org/rare-diseases/col4a1-a2-related-disorders/. doi: 10.1056/NEJMoa053727, 7. Front Aging Neurosci. Staals J, Makin SDJ, Doubal FN, Dennis MS, Wardlaw JM. Neurology. Exon mutations of the COL4A1 genes are responsible for a broad spectrum of cerebral, ocular, and systemic manifestations. The first time he came to meet us, Zeeva threw a sock at him. The site is secure. Urine analysis to test for blood or excess protein can be used to evaluate renal function and identify if the kidneys might be affected. Aura refers to additional neurological symptoms that occur with, or sometimes before, the development of the migraine headache. ACS Omega. 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. 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. 8600 Rockville Pike 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). At 2 years old, IV-6 presented obvious left hemiparesis but could move without help. Teaching families how to advocate for their loved ones and access medical information. Available at: https://www.ncbi.nlm.nih.gov/books/NBK7046/ Accessed January 28, 2019. With input from doctors, researchers, and the US Food & Drug Administration, NORD has created IAMRARE to facilitate patient-powered natural history studies to shape rare disease research and treatments. Other phenotypes include intracranial aneurysms, porencephaly, infantile hemiparesis, muscle cramps, optic nerve dysgenesis and secondary glaucoma. Facebook: https://www.facebook.com/Col4A1Foundation Please Note 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.) People with COL4A1-related brain small vessel disease also have leukoencephalopathy, which is a change in a type of brain tissue called white matter that can be seen with magnetic resonance imaging (MRI). The information on this site should not be used as a substitute for professional medical care or advice. COL4A1/A2-related disorders are caused by dominant mutations in the COL4A1 or COL4A2 genes. Neurology. Due to the rarity of the disease, there are no treatment trials that have been tested on a large group of patients. Available online at: https://www.ncbi.nlm.nih.gov/clinvar/variation/VCV000389182.3 (accessed March 20, 2020). The .gov means its official. Collagen type IV alpha 1 (COL4A1) silence hampers the invasion, migration and epithelial-mesenchymal transition (EMT) of gastric cancer cells through blocking Hedgehog signaling pathway. 2010 Aug;41(8):e513-8. Bull Acad Natl Med. doi: 10.1212/WNL.0000000000006567, PubMed Abstract | CrossRef Full Text | Google Scholar, 2. cuts under the microscope. (2012) 54:56974. The causative gene of HANAC is COL4A1 (13q34) encoding the alpha1 chain of collagen IV, a major component of basement membranes also involved in . COL4A1 Mutation in a Neonate With Intrauterine Stroke and Anterior Segment Dysgenesis. Services that may be beneficial for some affected individuals include medical, social, and/or vocational services such as special remedial education. Received: 06 January 2020; Accepted: 01 July 2020; Published: 11 September 2020. Born at term after a 39-week pregnancy, IV-3 had an unremarkable first clinical evaluation at 3 months. She has regular physical, speech, and occupational therapy. 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. Patients must rely on the personal and individualized medical advice of their qualified health care professionals before seeking any information related to their particular diagnosis, cure or treatment of a condition or disorder. 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. January 31, 2019 An MRI uses a magnetic field and radio waves to produce cross-sectional images of particular organs and bodily tissues, including the brain. COL4A1 -related brain small-vessel disease is characterized by weakening of the blood vessels in the brain. Pediatricians are physicians who specialize in the childhood disorders and are often the first to detect patients with COL4A1/A2-related disorders. Any muscle may be affected, and cramps usually last from a few seconds to a few minutes, although in some cases they can last for several hours. Eur J Paediatr Neurol. This site needs JavaScript to work properly. IV-5 had microcephaly without motor deficits, a language delay, a mental retardation (IQ of 62) that required adapted schooling, and severe hypermetropia. (2014) 15:16. Stroke. The management of COL4A1/A2-related disorders may require the coordinated efforts of a team of specialists. 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). The variability and severity of symptoms is significant and how COL4A1/A2-related disorders will potentially affect an individual can be unique. Gould Syndrome is an ultra rare genetic, multi-system disorder. Internet. Neurology. Aguglia U, Gambardella A, Breedveld GJ, Oliveri RL, Le Piane E, Messina D, et al. Phone: 202-588-5700. What does it mean if a disorder seems to run in my family? 1900 Crown Colony Drive The networks formed by the COL4A1 and COL4A2 proteins are called basement membranes and are present in every organ of the body. Still other individuals may not develop any symptoms until well into adulthood. All patients suffering from HANAC syndrome display retinal arteriolar tortuosity and occasional retinal hemorrhages. To date, over 50 pathogenic or likely pathogenic variants have been described in the COL4A1 gene, most of them missense (2). 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. Each child of an individual with a COL4A1-related disorder has a 50% chance of inheriting the pathogenic variant. COL4A1 codes for extracellular matrix proteins that form heterotrimers that are major components of nearly all organ basal membranes. Molecular Dynamics Investigation on the Effects of Protonation and Lysyl Hydroxylation on Sulfilimine Cross-links in Collagen IV. Basement membranes without these networks are unstable, leading to weakening of the tissues that they surround. Bone. In addition the whole spectrum of the phenotype is not yet known and there are many asymptomatic patients. Neurology. came with risks and was the hardest decision we had ever faced, yet we felt 100 This first-of-its-kind assistance program is designed for caregivers of a child or adult diagnosed with a rare disorder. *Correspondence: Pasquale Scoppettuolo, Pasquale.scoppettuolo@gmail.com, https://www.ncbi.nlm.nih.gov/clinvar/variation/VCV000389182.3, Creative Commons Attribution License (CC BY). Many patients with COL4A1 and COL4A2 mutations have additional signs and symptoms that do not include the cerebral vasculature. To better define pathology caused by Col4a1 mutations, we characterized myopathy in two different Col4a1 mutant mouse strainsCol4a1 ex41 and Col4a1 G394V.We selected these strains from an allelic series of Col4a1 mutant mice because they showed the most severe myopathy according to NPN quantification in quadriceps while having different effects on [1(IV)] 2 2(IV) secretion. Matrix Biol. For example, if the mutation arises during the formation of the sperm or the egg, then all of the cells that make up the child will carry the mutation. (19). Childhood presentation of COL4A1 mutations. It is important to discuss these concepts with a genetic counselor and understand their implications. III-3 was asymptomatic but for severe hypermetropia and bilateral cataracts. The COL4A1 gene has 52 exons and most of the pathogenic variants are distributed across exons 10 to 47 in the triple-helix domain. The conditions in this group have a range of signs and symptoms that involve fragile blood vessels. It is passed through families in a autosomal dominant fashion. Clipboard, Search History, and several other advanced features are temporarily unavailable. What are the different ways a genetic condition can be inherited? National Institute of Neurological Disorders and Stroke. Disclaimer. (2010) 14:1827. Neurology. Neurology. HANAC syndrome is caused by genetic changes in the COL4A1 gene. Gould Syndrome is a rare, genetic, multi-system disorder. A novel COL4A1 gene mutation results in autosomal dominant non-syndromic congenital cataract in a Chinese family. eCollection 2022 Nov 8. The p.Gly743Val variant is a conservative substitution that occurs in a position highly conserved across species (SIFT analysis: DeleteriousScore 0, median: 4.22, highly conserved nucleotide and amino acid, up to Tetraodon considering 11 species) and affects a crucial and abundant residue within the triple-helix-forming collagenous domain of the protein, which consist of long stretches of Gly-X-Y repeats. 2012;322:25-30. https://www.ncbi.nlm.nih.gov/pubmed/22868088, Shah S, Ellard S, Kneen R, et al. Phone: 203-263-9938 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. government site. Maybe try a search? 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 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. Summary: Symptoms of the following disorders can be similar to those of COL4A1/A2-related disorders. Gould DB, Phalan FC, van Mil SE, Sundberg JP, Vahedi K, Massin P, et al. doi: 10.1212/WNL.0b013e3181c3fd12, 9. As a result, the skin around the affected area may turn white or blue for a brief period of time and the area may tingle or throb. Quincy, MA 02169 1779 Massachusetts Avenue Slavotinek AM, Garcia ST, Chandratillake G, Bardakjian T, Ullah E, Wu D, et al. The information on this site should not be used as a substitute for professional medical care or advice. Most individuals diagnosed with a COL4A1-related disorder have an affected parent. Surgery or endovascular therapy can be used to treat intracranial hemorrhage. 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. PS: wrote thi paper and performed the review of the literature under the supervision of GN. The blood vessels as well as thin sheet-like structures called basement membranes that separate and support cells are weakened and more susceptible to breakage. (2014) 11:3612. The proportion of cases caused by a de novopathogenic variant is estimated to be at least 27%. The X and Y chromosomes are called the sex chromosomes and the rest all are called 'autosomes'. 2012;21:R97-R110. doi: 10.2214/ajr.149.2.351, 19. As the name suggests, mutations in the COL4A1 gene cause COL4A1-related brain small vessel disease. Neurology. These proteins have very restricted expression and Alport Syndrome primarily affects the kidneys with variable involvement of the eye and cochlea (hearing). When an individual tests positive for a mutation but does not manifest the effects, it is referred to as having incomplete or reduced penetrance. (2014) 252:178994. Jeanne M, Gould DB. (2015) 84:91826. Congenital Cephalic Disorders doi: 10.1212/WNL.0000000000000837, 20. 2014 Mar;261(3):500-3. doi: 10.1007/s00415-013-7224-4. Focke JK, Veltkamp R, Bauer P, Kraemer M. J Neurol. Yet, five siblings, showing mild phenotype even in the second generation support a Mendelian transmission with variable expressivity and no other mechanism. (2010) 75:7479. functional hemispherectomy. seizure activity. After the COL4A1 mutation was found, systemic manifestations of COL4A1 mutations were investigated. The COL4A1 stroke syndrome. Further refinement of COL4A1 and COL4A2 related cortical malformations. Some people with COL4A1-related brain small-vessel disease have an eye abnormality called Axenfeld-Rieger anomaly. For example, treatment may include physical therapy, speech therapy, anti-convulsant medications for seizures, and a shunt to treat hydrocephalus by draining excess fluid from the skull. Similar blood vessel weakness and breakage occurs in the eyes of some affected individuals. This is not specific to COL4A1/A2-related disorders, and is a sign of many different types of muscle disease. Suite 500 Collagen alpha-1(IV) chain (COL4A1) is a protein that in humans is encoded by the COL4A1 gene on chromosome 13. See our, COL4A1-related brain small-vessel disease, URL of this page: https://medlineplus.gov/genetics/condition/col4a1-related-brain-small-vessel-disease/. Please enable it to take advantage of the complete set of features! 2009 Jun 25 [updated 2016 Jul 7]. 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. The latest research shows that insufficient COL4A1/A2 in basement membranes damages different tissues in very different ways. 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. At 1 month of age, a neuropediatric examination disclosed normal neck muscle tonus, normal Moro reflex, bilateral placing reaction, and open hands. Researchers are still trying to determine whether there are any specific genotype-phenotype correlations in COL4A1/A2-related disorders. Washington, DC 20036 However, these findings can be observed independently or in combinations, in many patients with COL4A1 and COL4A2 mutations. Phone: 202-588-5700. Sibon I, Coupry I, Menegon P, Bouchet JP, Gorry P, Burgelin I, Calvas P, http://www.centerwatch.com/, For information about clinical trials conducted in Europe, contact: Understanding what it has taken to get her to this point, though, is close to unimaginable. 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. 2009;73:1873-1882. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2881859/, Mao, M, Alavi MV, Labelle-Dumais, C, Gould DB. The disorder causes many symptoms, not the least of which are strokes and epilepsy. 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). This can occur if the carrier is a mosaic which means that some cells carry the mutation while other cells do not. Fax: 203-263-9938, Washington, DC Office GeneReviews. Stroke subtype, vascular risk factors, and total MRI brain small-vessel disease burden. 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/. Background: COL4A1 mutations cause familial porencephaly, infantile hemiplegia, cerebral small vessel disease (CSVD), and hemorrhagic stroke. Novel mutations in three families confirm a major role of COL4A1 in hereditary porencephaly. A diagnosis can be confirmed through molecular genetic testing. Gould Syndrome - COL4A1 - COL4A2 genes - Gould Syndrome Foundation Gould Syndrome Foundation 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. People listened to us and to Zeeva in a very different and proactive way. Suite 500 Neuropsychological tests disclosed language delay and learning difficulties requiring speech therapy at the age of 9 years. In the brain, intracerebral hemorrhage is the most frequent phenotype. 1900 Crown Colony Drive Ten months later, the left hemiparesis was observed with a lack of voluntary prehension on his left side without spasticity. can also contribute. We provide education, advocacy, and resources for families and individuals affected. Years published: 2019. Jeanne M, Gould DB. Hum Mol Genet. 2022 Sep;269(9):5153-5156. doi: 10.1007/s00415-022-11111-0. (18) and Staals et al. Cysts can also form in one or both kidneys, and the cysts may grow larger over time. Changing lives of those with rare disease. Firstly, it segregates within the family with the phenotype. The human phenotypes are extremely variable between patients and between families, with disease onset as early as in the fetal period. Plaisier E, Gribouval O, Alamowitch S, Mougenot B, Prost C, Verpont MC, et al. Thats not to say Zeeva hasnt had to work hard since the surgery. Neurovascular Alterations in Vascular Dementia: Emphasis on Risk Factors. Neuropediatrics. [Hereditary angiopathy with nephropathy, aneurysms and muscle cramps (HANAC): a new basement membrane-disease associated with mutations of the COL4A1 gene]. COL4A1 is an essential component for basal membrane stability. doi: 10.1111/cge.12379, 13. (2011) 42:13. While there are other explanations, parental mosaicism should be considered. But she is learning to read, enjoys swimming, horseback riding, and is a glass jewelry and pottery artist. NORD is a registered 501(c)(3) charity organization. (2014) 34:757. Stay Informed With NORDs Email Newsletter, Launching Registries & Natural History Studies. Stroke. Affected individuals may have no observable symptoms or only isolated migraines with aura. Zeeva is one of fewer than 150 people in the world with a rare disease called Gould Syndrome or COL4A1/A2. Federal government websites often end in .gov or .mil. Individuals with this condition are at increased risk of having more than one stroke in their lifetime. COL4A1/A2-related disorders can also be associated with a variety of abnormalities affecting the front or back of the eyes. The degree of mosaicism is highly variable ranging from only a small percent of cells with the mutation to nearly all cells carrying the mutation and depends on the stage during development that the mutation occurred. Hereditary cerebral small vessel diseases: a review. Front. doi: 10.1007/s10897-008-9169-9, 16. The type IV collagens are encoded by six different genes (COL4A1, COL4A2, COL4A3, COL4A4, COL4A5 and COL4A6). Am J Med Genet. During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of certain tissue structures. NORD and MedicAlert Foundation have teamed up on a new program to provide protection to rare disease patients in emergency situations. 2007 Aug;62(2):177-84. doi: 10.1002/ana.21191. What is the prognosis of a genetic condition? Muscle cramps can be spontaneous or triggered by exercise. Changing lives of those with rare disease. Plaisier E, Chen Z, Gekeler F, Benhassine S, Dahan K, Marro B, Alamowitch S,