10.1161/STROKEAHA.110.581918. Epub 2014 Jan 5. 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. 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. What does it mean if a disorder seems to run in my family? 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. MedlinePlus also links to health information from non-government Web sites. Fragile or damaged blood vessels or basement membranes in the kidneys can lead to blood in the urine (hematuria). Compared to other COL4A1-related disorders, the brain is only mildly affected in HANAC syndrome. Summary: Dr. Madsen suggested Zeeva have an operation called a About half of people with this condition 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). J Genet Couns. doi: Neurology. The information on this site should not be used as a substitute for professional medical care or advice. COL4A1/A2-related disorders are dominant genetic disorders. 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. doi: 10.1038/nmeth.2890, 22. Some individuals develop cysts on the kidney. Alamowitch S, Plaisier E, Favrole P, Prost C, Chen Z, Van Agtmael T, Marro B, (2010). Some of the patient advocacy organizations listed in the Resources section below provide support and information to affected individuals and their families. Exon mutations of the COL4A1 genes are responsible for a broad spectrum of cerebral, ocular, and systemic manifestations. 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). We believe that the variant p.Gly743Val is likely pathogenic for several reasons. Because the collagen is found throughout the body, COL4A1/A2 affects many organ systems, including the brain, kidneys, eyes, and muscles. Our experience with Boston Childrens was very different from the other places we had been for epilepsy and neurology treatment. 2015;17:843-853. https://www.nature.com/articles/gim2014210, Yoneda Y, Haginoya K, Kato M, et al. Aura refers to additional neurological symptoms that occur with, or sometimes before, the development of the migraine headache. Ann Neurol. Vilain C, Van Regemorter N, Verloes A, David P, Van Bogaert P. Neuroimaging fails to identify asymptomatic carriers of familial porencephaly. (2007) 357:268795. This analysis represents a subanalysis of the 35 out of 60 children <=18 years of age who reported a history of seizures. HANAC syndrome is caused by genetic changes in the COL4A1 gene. The X and Y chromosomes are called the sex chromosomes and the rest all are called 'autosomes'. The disorder causes many symptoms, not the least of which are strokes and epilepsy. doi: 10.1001/archophthalmol.2010.42, 10. 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). 2018;61:765-772. 2010 Oct;152A(10):2550-5. doi: 10.1002/ajmg.a.33659. We therefore began our analysis of mutant Col4a1 G498V mice by examining the retinal vascular network at three and nine months of age. IV-3 and IV-6 are closely followed by a neuropediatrician (VW). It is passed through families in a autosomal dominant fashion. For example, Type I collagen mutations cause Osteogenesis Imperfecta (brittle bone disease), Type II collagen mutations cause chondrodysplasias (defects of cartilage) and mutations in Type III collagen cause a form of Ehlers-Danlos Syndrome. 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. The causative gene of HANAC is COL4A1 (13q34) encoding the alpha1 chain of collagen IV, a major component of basement membranes also involved in . for the triple helical CB3[IV] domain. 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). Liu X, Yang Q, Tang L, He J, Tian D, Wang B, Xie L, Li C, Fan D. Front Neurol. 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). 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. government site. Aguglia U, Gambardella A, Breedveld GJ, Oliveri RL, Le Piane E, Messina D, et al. 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. 30. Individuals with HANAC syndrome also experience a variety of eye problems. Together, these studies suggest that certain unknown variants of COL4A1 and COL4A2 might contribute to chronic vascular dysfunction. (D) III- 3Brain MRI showed small asymptomatic lesions in white matter. Axenfeld-Rieger anomaly and cataract can cause impaired vision. This site needs JavaScript to work properly. If the mutation arises after fertilization, then some cells will carry the mutation and others will not this is called mosaicism. Rouaud T, Labauge P, Lasserve ET, Mine M, Coustans M, Deburghgraeve V, et al. The management of COL4A1/A2-related disorders may require the coordinated efforts of a team of specialists. Urine analysis to test for blood or excess protein can be used to evaluate renal function and identify if the kidneys might be affected. INTERNET 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. 128:4839. If either parent also carries the mutation, it is considered inherited. Mutations in the gene have been linked to diseases of the brain, muscle, kidney, eye, and cardiovascular system. Pediatricians are physicians who specialize in the childhood disorders and are often the first to detect patients with COL4A1/A2-related disorders. This condition causes mutations in genes that produce a specific type of collagen. N Engl J Med. (2015) 88:46873. Muscle cramps experienced by most people with HANAC syndrome typically begin in early childhood. At the age of 12, IV-3 underwent cerebral palsy quality of life (CPQoL) questionnaires in which they expressed a satisfactory quality of life and a good relationship with other children. Available at: https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Cephalic-Disorders-Fact-Sheet Accessed January 28, 2019. For the nucleotide numbering, the HVGS terms (www.hgvs.org) were applied with the nucleotide A of the ATG startcodon = c.1. It is possible that insufficient collagen in the basement membrane predisposes blood vessels in the brain to leak or rupture. (2017) 377:111931. 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. Type IV collagen molecules attach to each other to form complex protein networks. Some individuals do not have any observable symptoms (asymptomatic); others can develop severe, even life-threatening complications. 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. He underwent at birth neurosonography for axial hypotonia that revealed ventricular asymmetry and right frontotemporal dilatation (Figure 3). (2006) 43:4905. doi: 10.1016/j.matbio.2016.10.003, 23. GeneReviews. 1 Survivors often have a severely diminished quality of life, require long-term care, and are at high risk . NORD is a registered 501(c)(3) charity organization. Axenfeld-Rieger anomaly involves underdevelopment and eventual tearing of the colored part of the eye (iris) and a pupil that is not in the center of the eye. The .gov means its official. (2020). doi: 10.1212/WNL.0b013e3181eee440, 28. He also wanted to remove a shunt that was implanted in Gould Syndrome is a rare, genetic, multi-system disorder. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Contact a health care provider if you have questions about your health. Neurol. doi: 10.1056/NEJMoa1707914, 6. 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. Zeeva is one of fewer than 150 people in the world with a rare disease called Gould Syndrome or COL4A1/A2. 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. The cells of the retina trigger nerve impulses that run from the optic nerve to the brain to form sight. (19). 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/. cutting tissue called the corpus callosum, then make some additional delicate doi: 10.1056/NEJMoa071906, 14. Mutations in COL4A3, COL4A4 and COL4A5 were found in the early 1990's in patients with Alport Syndrome. This condition causes mutations in genes that produce a specific type of collagen. IV-3 was diagnosed with ventriculomegaly in utero. By continuing to use this website, you agree to the Terms of Service & Privacy Policy. Copyright 2023 by Gould Syndrome Foundation -, https://rarediseases.org/rare-diseases/col4a1-a2-related-disorders/. 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. The COL4A2 test was negative. Eur J Med Genet. Molecular analysis was performed on a gDNA level by means of PCR amplification of all the coding exons and the flanking intron region. IV-5Brain MRI revealing porencephalic cyst of frontal horn of lateral right ventricle (C). This is not specific to COL4A1/A2-related disorders, and is a sign of many different types of muscle disease. Zagaglia S, Selch C, Nisevic JR, Mei D, Michalak Z, Hernandez-Hernandez L, et al. Unauthorized use of these marks is strictly prohibited. Affected individuals may also experience seizures and migraine headaches accompanied by visual sensations known as auras. Danbury, CT 06810 Molecular genetic testing can detect variations in the COL4A1 and COL4A2 genes that cause these disorders, but is available only as a diagnostic service at specialized laboratories. Changing lives of those with rare disease. The COL4A1 gene mutations that cause COL4A1-related brain small-vessel disease result in the production of a protein that disrupts the structure of type IV collagen. ClinVar; [VCV000389182.3]. What does it mean if a disorder seems to run in my family? . functional hemispherectomy. Comparisons may be useful for a differential diagnosis: CADASIL is a rare genetic disorder affecting the small blood vessels in the brain. Basement membranes without these networks are unstable, leading to weakening of the tissues that they surround. The COL4A1 gene mutations that cause HANAC syndrome result in the production of a protein that disrupts the structure of type IV collagen. These types of correlations can be difficult to detect in patients because of the broad genetic variability in humans. Here we report a family in which three siblings presented severe hypermetropia and porencephaly. While there are other explanations, parental mosaicism should be considered. *Correspondence: Pasquale Scoppettuolo, Pasquale.scoppettuolo@gmail.com, https://www.ncbi.nlm.nih.gov/clinvar/variation/VCV000389182.3, Creative Commons Attribution License (CC BY). When this enzyme is elevated, it is a sign of muscle damage. (2014) 11:3612. People with this condition may have a bulge in one or multiple blood vessels in the brain (intracranial aneurysms). 2012;54:569-574. https://www.ncbi.nlm.nih.gov/pubmed/22574627, Lanfranconi S, Markus HS. doi: 10.1038/jp.2013.135, 29. Childhood presentation of COL4A1 mutations. ACS Omega. 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. The conditions in this group have a range of signs and symptoms that involve fragile blood vessels. One patient (IV-3) was treated for spasticity and seizures with valproic acid. No microbleeds or cystic cavities were found. Some individuals with COL4A1-related brain small-vessel disease do not have any signs or symptoms of the condition. 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). Type IV Collagens and Basement Membrane Diseases: Cell Biology and Pathogenic Mechanisms. 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. Hereditary angiopathy with nephropathy, aneurysms, and muscle cramps (HANAC) syndrome is part of a group of conditions called the COL4A1 -related disorders. 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). The variant was confirmed by bidirectional fluorescence DNA sequencing (Sanger method). He was confident this would reduce or stop the Front Aging Neurosci. Genet Med. The limitations include the limited number of tested members (only two generations) due to a large family spread over Europe and not fully accessible. (2006) 354:148996. Curr Med Chem. COL4A1 -related brain small-vessel disease is part of a group of conditions called the COL4A1 -related disorders. Raynaud phenomenon is typically triggered by changes in temperature and usually causes no long term damage. official website and that any information you provide is encrypted Yet, five siblings, showing mild phenotype even in the second generation support a Mendelian transmission with variable expressivity and no other mechanism. Email: [emailprotected], Some current clinical trials also are posted on the following page on the NORD website: Orignac I, Dousset V, Lacombe D, Orgogozo JM, Arveiler B, Goizet C. COL4A1 Neurology. COL4A1-related brain small-vessel disease is a rare condition, although the exact prevalence is unknown. In the front of the eye, patients can have abnormally small eyes (microphthalmia), cataracts (cloudy lenses), and anterior segment dysgenesis (Axenfeld-Rieger). Since fewer than 100 families have been reported, the exact prevalence of COL4A1-related disorders is not well-established. 2017;155:45-57. https://www.ncbi.nlm.nih.gov/pubmed/28254515, Alavi MV, Mao M, Pawlikowski BT, et al. Washington, DC 20036 The retina is the light-sensitive membrane that lines the inside of the eyes. https://www.clinicaltrialsregister.eu/, JOURNAL ARTICLES (2014) 252:178994. However, there are exceptions that depend on precisely when and where the mutation arose. (2002) 112:198202. Rarely, affected individuals will have a condition called Raynaud phenomenon in which the blood vessels in the fingers and toes temporarily narrow, restricting blood flow to the fingertips and the ends of the toes. Quincy, MA 02169 These proteins have very restricted expression and Alport Syndrome primarily affects the kidneys with variable involvement of the eye and cochlea (hearing). She had seizures every day, couldnt gain weight, sleep right, or generally enjoy her life. The team may eventually include pediatric neurologists (diagnose and treat disorders of the brain, nerves and nervous system in children); ophthalmologists (who specialize in eye disorders) hematologists (who specialize in blood disorders); cardiologists (who specialize in heart disorders, nephrologists (who specialize in kidney disorders) and other healthcare professionals may need to systematically and comprehensively plan treatment. (2015) 84:91826. The disorder causes many symptoms, not the least of which are strokes and epilepsy. Neurology. Neurology. COL4A1/A2-related disorders are rare, genetic, multi-system disorders. COL4A1 disorder is probably largely underestimated because of its multisystem and variable phenotype. To date, over 50 pathogenic or likely pathogenic variants have been described in the COL4A1 gene, most of them missense (2). doi: 10.1212/01.WNL.0000123113.46672.68, 25. Cavalin M, Mine M, Philbert M, et al. For instance, retinal arteriolar tortuosity relates to mutations in the amino-terminal one-third of the protein while mutations causing cataracts and ocular morphologic alterations are more likely to occur, closer to the carboxy terminus (22), like the variant we report. Not only did Dr. Madsen, help heal Zeevas brain, but he was instrumental in supporting us as we founded the Gould Syndrome Foundation, a 501(c)(3) non-profit that promotes education, advocacy, and medical advancements in Gould Syndrome, COL4A1/COL4A2 diseases. doi: 10.1002/ana.23736, 4. It looks like nothing was found at this location. Dev Med Child Neurol. COL4A1 mutations as a monogenic cause of cerebral Surgery or endovascular therapy can be used to treat intracranial hemorrhage. Arterial retinal tortuosity can cause episodes of bleeding within the eye following any minor trauma to the eye, leading to temporary vision loss. sharing sensitive information, make sure youre on a federal Unable to load your collection due to an error, Unable to load your delegates due to an error. (2014) 15:16. Fax: 203-263-9938, Washington, DC Office Feb;24(1):63-8. doi: 10.1097/WCO.0b013e32834232c6. 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. Careers. (2015) 17:40524. An official website of the United States government. This is called genotype-phenotype correlation. Phone: 617-249-7300, Danbury, CT office doi: 10.1111/cge.12379, 13. In: Adam MP, Everman DB, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. Progressive cerebral atrophies in three children with COL4A1 mutations. J Neurol Sci. IV-6 was born at 35 weeks after a pregnancy marked by gestational diabetes. COL4A1 and COL4A2 mutations and disease: insights into pathogenic mechanisms and potential therapeutic targets. A novel COL4A1 gene mutation results in autosomal dominant non-syndromic congenital cataract in a Chinese family. (2009) 73:187382. Coupry I, Sibon I, Mortemousque B, Rouanet F, Mine M GC. The variability and severity of symptoms is significant and how COL4A1/A2-related disorders will potentially affect an individual can be unique. Am J Neuroradiol. Gould Syndrome is diagnosed following a genetic test revealing a mutation in COL4A1 or COL4A2. Children with the most severe brain malformations may have: Intellectual impairment Seizures Hydrocephalus Spasticity People who have a disorder of the corpus callosum typically have: Neurovascular Alterations in Vascular Dementia: Emphasis on Risk Factors. 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. Neurology. Nearly half of these participants were diagnosed with infantile spasms. U.S. Department of Health and Human Services, Brain small-vessel disease with hemorrhage. Shah S, Kumar Y, McLean B, Churchill A, Stoodley N, Rankin J, et al. Phone: 202-588-5700. (2015) 17:84353. (1987) 8:4216. Colin E, Sentilhes L, Sarfati A, Mine M, Guichet A, Ploton C, et al. Glaucoma is initially treated with topical medications and, if medical therapy is unsuccessful, surgery. Alamowitch S, Plaisier E, Favrole P, Prost C, Chen Z, Van Agtmael T, et al. 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. 2013;73:48-57. https://www.ncbi.nlm.nih.gov/pubmed/23225343, Kuo DS, Labelle-Dumais C, Gould DB. 2018;91:e2078-e2088. Clin Neurol Neurosurg. Stroke is a leading cause of death and serious long-term disability in developed nations. 2009 Jun 25 [updated 2016 Jul 7]. (2014) 83:122834. COL4A1 encodes type IV collagen 1 chain, a crucial component of nearly all basement membrane including vasculature, renal glomerule and ocular structures. IV-5 had microcephaly without motor deficits, a language delay, a mental retardation (IQ of 62) that required adapted schooling, and severe hypermetropia. Mutations in the COL4A1 gene cause HANAC syndrome. This first-of-its-kind assistance program is designed for caregivers of a child or adult diagnosed with a rare disorder. In the eye, patients may have retinal arteriolar tortuosities and retinal hemorrhages or anterior segment dysgenesis. Neurology. 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. cuts under the microscope. (2008) 17:42433. Xia XY, Li N, Cao X, Wu QY, Li TF, Zhang C, et al. 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). Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, et al. Stroke. National Institute of Neurological Disorders and Stroke. The inheritance pattern is autosomal dominant (14) and age-dependent with almost 100% penetrance. Standardized human pedigree nomenclature: update and assessment of the recommendations of the National Society of Genetic Counselors. However, in people with HANAC syndrome, these aneurysms typically do not burst. Probands' father had severe hypermetropia and bilateral cataracts. Please enable it to take advantage of the complete set of features! This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). Collagen alpha-1(IV) chain (COL4A1) is a protein that in humans is encoded by the COL4A1 gene on chromosome 13. doi: 10.1136/jmg.2005.035584, 15. She has regular physical, speech, and occupational therapy. Danbury, CT 06810 This variant highlights that the COL4A1 mutation should be sought in cases of familial ophthalmologic pathologies associated with congenital porencephaly or early onset leukoencephalopathy. Clinical Testing and Workup Clinical case reports suggest a syndrome with characteristic core findings; however, much about the disorder is not fully understood. In some people, serious, life-threatening complications may occur in infancy; in others, only minor complications may occur and intelligence is unaffected. Because the collagen is found throughout the body, COL4A1/A2 affects many organ systems, including the brain, kidneys, eyes, and muscles. It is ubiquitously expressed in many tissues and cell types. Zeeva woke up after a ten-hour procedure, opened her eyes, and it felt like we were seeing her for the first time. No use, distribution or reproduction is permitted which does not comply with these terms. mutations: a novel genetic multisystem disease. The COL4A1 stroke syndrome. Cerebrovascular disease related to COL4A1 mutations in HANAC syndrome. (2010) 14:1827. Epub 2010 Jun 17. Systemic work-up including renal function, CK levels, urinary sediment test, and renal ultrasound proved unremarkable. 2010 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. Researchers are still trying to determine whether there are any specific genotype-phenotype correlations in COL4A1/A2-related disorders. 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. One year later, right hemiparesis became clinically evident with a lack of right voluntary hand prehension in association with right hemineglect. Prenatal clinical manifestations in individuals with COL4A1/2 variants. Firstly, it segregates within the family with the phenotype. In people with HANAC syndrome, the vasculature and other tissues within the kidneys, brain, muscles, eyes, and throughout the body weaken. FOIA Please note that NORD provides this information for the benefit of the rare disease community. Treatment A Podcast For The Rare Disease Community, Policy Statements & Letters to Policymakers. Bethesda, MD 20894, Web Policies Yoneda Y, Haginoya K, Kato M, Osaka H, Yokochi K, Arai H, et al. Affected infants and children can exhibit delays in reaching developmental milestones and varying degrees of intellectual disability. At least six affected families have been described in the scientific literature. (2018) 91:e207888. 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. 1. 2010;41:e513-518. View CNBC interview with NORDs Peter Saltonstall and Boston Childrens Dr. Olaf Bodamer emphasizing the importance of investment in rare diseases. 2022 Oct 26;7(44):39680-39689. doi: 10.1021/acsomega.2c03360. It is important to discuss these concepts with a genetic counselor and understand their implications. Cephalic Disorders Fact Sheet. HHS Vulnerability Disclosure, Help 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. Copyright 2023 NORD National Organization for Rare Disorders, Inc. All rights reserved. At 1 month of age, a neuropediatric examination disclosed normal neck muscle tonus, normal Moro reflex, bilateral placing reaction, and open hands. 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. Lecordier S, Manrique-Castano D, El Moghrabi Y, ElAli A. National Library of Medicine Drugs that prevent irregular heartbeats (anti-arrhythmic medications) are used to treat supraventricular arrythmia. PMC These aneurysms have the potential to burst, causing bleeding within the brain (hemorrhagic stroke). Background: COL4A1 mutations cause familial porencephaly, infantile hemiplegia, cerebral small vessel disease (CSVD), and hemorrhagic stroke. 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.