can also contribute. 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. 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. The variant was found in IV-3 and IV-5 and not in asymptomatic relatives (III-4, IV-1, IV-4). For example, the position of the mutation along the length of the protein can influence the severity of cerebrovascular disease and mutations in functional subdomains can influence the likelihood of tissue-specific involvement (for example, muscle). When we didnt feel we had any options left for treatment, Cephalic Disorders Fact Sheet. 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. III-3 was informed of the genetic diagnosis and is now regularly followed and screened for cataracts and brain aneurysms. These aneurysms have the potential to burst, causing bleeding within the brain (hemorrhagic stroke). The COL4A1 gene mutations that cause HANAC syndrome result in the production of a protein that disrupts the structure of type IV collagen. While there are other explanations, parental mosaicism should be considered. Epub 2022 Apr 14. How are genetic conditions treated or managed? Disclaimer. Available at: https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Cephalic-Disorders-Fact-Sheet Accessed January 28, 2019. A diagnosis can be confirmed through molecular genetic testing. Our experience with Boston Childrens was very different from the other places we had been for epilepsy and neurology treatment. doi: 10.2214/ajr.149.2.351, 19. (2013) 73:4857. IV-3 was diagnosed with ventriculomegaly in utero. No patient had cramps, cardiac symptoms, or abnormalities or Raynaud phenomenon. 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. Novel mutations in three families confirm a major role of COL4A1 in hereditary porencephaly. Advanced imaging techniques can include computerized tomography (CT) scanning and magnetic resonance imaging (MRI). MeSH Migraines can occur with or without aura. Yet, five siblings, showing mild phenotype even in the second generation support a Mendelian transmission with variable expressivity and no other mechanism. (19). Teaching families how to advocate for their loved ones and access medical information. Various treatments have been reported in the medical literature as part of single case reports or small series of patients. (2015) 88:46873. 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. (1982) 40:5679. Mutations in Col4a1 cause perinatal cerebral hemorrhage and porencephaly. The causative gene of HANAC is COL4A1 (13q34) encoding the alpha1 chain of collagen IV, a major component of basement membranes also involved in . Ten months later, the left hemiparesis was observed with a lack of voluntary prehension on his left side without spasticity. Because the collagen is found throughout the body, COL4A1/A2 affects many organ systems, including the brain, kidneys, eyes, and muscles. Unable to load your collection due to an error, Unable to load your delegates due to an error. HANAC syndrome is characterized by angiopathy, which is a disorder of the blood vessels. 2014 Mar;261(3):500-3. doi: 10.1007/s00415-013-7224-4. Neurology. Neurologic phenotypes associated with COL4A1/2 mutations: expanding the spectrum of disease. What does it mean if a disorder seems to run in my family? Rouaud T, Labauge P, Lasserve ET, Mine M, Coustans M, Deburghgraeve V, et al. These protein networks are the main components of basement membranes, which are thin sheet-like structures that separate and support cells in many tissues. (1987) 8:4216. Ann Neurol. Purpose of review: doi: 10.1212/01.WNL.0000123113.46672.68, 25. NORD and MedicAlert Foundation have teamed up on a new program to provide protection to rare disease patients in emergency situations. 2008 May;192(5):971-84; discussion 984-6. As a result, type IV collagen molecules cannot attach to each other to form the protein networks in basement membranes. Cerebrovascular disease related to COL4A1 mutations in HANAC syndrome. The COL4A1 gene has 52 exons and most of the pathogenic variants are distributed across exons 10 to 47 in the triple-helix domain. Exon mutations of the COL4A1 genes are responsible for a broad spectrum of cerebral, ocular, and systemic manifestations. eCollection 2021. J Med Genet. Xia XY, Li N, Cao X, Wu QY, Li TF, Zhang C, et al. Washington, DC 20036 In people with HANAC syndrome, angiopathy affects several parts of the body. (2014) 83:122834. These genes are the blueprints for two proteins that wind together like a long rope inside cells. The type IV collagens are encoded by six different genes (COL4A1, COL4A2, COL4A3, COL4A4, COL4A5 and COL4A6). (2018) 91:e207888. Given the variable expressivity of these mutations, COL4A1/A2-related disorders are likely under diagnosed and the exact number of people who have these disorders is unknown. 1900 Crown Colony Drive Zagaglia Selch C, Nisevic JR, et al. 1900 Crown Colony Drive Zeeva woke up after a ten-hour procedure, opened her eyes, and it felt like we were seeing her for the first time. Sci Rep. 2016;6:18602. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728690/, Rannikmae K, Davies G, Thomson PA, et al. (2012) 54:56974. Bennett RL, French KS, Resta RG, Doyle DL. The pathogenic mechanisms of COL4A1 mutations are not fully elucidated and may vary according to the mutation type, the affected exon (mutations responsible for systemic HANAC syndrome cluster at exon 24 and 25), the position of the mutation within the triple-helix domain, and the mutation location. The strengths of our study are the extensive systemic work-up, the 5-year neurological follow-up, and the pluridisciplinary approach. The limitations include the limited number of tested members (only two generations) due to a large family spread over Europe and not fully accessible. In: Adam MP, Everman DB, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. To use the sharing features on this page, please enable JavaScript. We each inherit a full complement on autosomes from each of our parents giving us two copies of each gene. NORD is a registered 501(c)(3) charity organization. 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. 2009;73:1873-1882. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2881859/, Mao, M, Alavi MV, Labelle-Dumais, C, Gould DB. Clinical Testing and Workup Feb;24(1):63-8. doi: 10.1097/WCO.0b013e32834232c6. This is not specific to COL4A1/A2-related disorders, and is a sign of many different types of muscle disease. Your support helps to ensure everyones free access to NORDs rare disease reports. The retina is the light-sensitive membrane that lines the inside of the eyes. Next generation sequencing uncovers a missense mutation in COL4A1 as the cause of familial retinal arteriolar tortuosity. However, it is also very likely that basement membrane defects also contribute to abnormal signaling and function of cells that form blood vessels in the brain and elsewhere. She, then, developed seizures which were controlled by valproic acid. Lenses corrected for hypermetropia. 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. COL4A1 and COL4A2 are on Chr. COL4A1 encodes type IV collagen 1 chain, a crucial component of nearly all basement membrane including vasculature, renal glomerule and ocular structures. The https:// ensures that you are connecting to the Individuals with this condition are at increased risk of having more than one stroke in their lifetime. 2022 Sep;269(9):5153-5156. doi: 10.1007/s00415-022-11111-0. Nearly half of these participants were diagnosed with infantile spasms. 2009 Dec 1;73(22):1873-82. doi: 10.1212/WNL.0b013e3181c3fd12. After the COL4A1 mutation was found, systemic manifestations of COL4A1 mutations were investigated. Dev Med Child Neurol. COL4A1 Mutation in a Neonate With Intrauterine Stroke and Anterior Segment Dysgenesis. COL4A1-related brain small-vessel disease is a rare condition, although the exact prevalence is unknown. PMC Childhood presentation of COL4A1 mutations. Dr. Madsen suggested Zeeva have an operation called a CADASIL patients can experience progressive memory loss, deterioration of intellectual abilities and loss of balance with a progressive worsening of these symptoms, but symptoms are usually less severe and occur later in life. I cannot describe the feeling of seeing your child healed. Changing lives of those with rare disease. His bedside manner was incredible. 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. She has regular physical, speech, and occupational therapy. In addition the whole spectrum of the phenotype is not yet known and there are many asymptomatic patients. Type IV collagen is an important component of basement membranes in many tissues, especially blood vessels 1-6. Sibon I, Coupry I, Menegon P, Bouchet JP, Gorry P, Burgelin I, Calvas P, (2020). COL4A1 Syndrome CADASIL doi: 10.1038/gim.2015.30, 21. This is called genotype-phenotype correlation. Ann Neurol. Affected individuals may have no observable symptoms or only isolated migraines with aura. 2021 Sep 10;13:727590. doi: 10.3389/fnagi.2021.727590. Copyright 2020 Scoppettuolo, Ligot, Wermenbol, Van Bogaert and Naeije. COL4A1 is a subunit of the type IV collagen and plays a role in angiogenesis. 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. (2006) 354:148996. 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. Quincy, MA 02169 COL4A1/A2-related disorders are rare, genetic, multi-system disorders. Plaisier E, Gribouval O, Alamowitch S, Mougenot B, Prost C, Verpont MC, et al. Alamowitch S, Plaisier E, Favrole P, Prost C, Chen Z, Van Agtmael T, et al. Treatment Before 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). It is ubiquitously expressed in many tissues and cell types. sharing sensitive information, make sure youre on a federal Children inherit a full complement of chromosomes from each of their parent and so we carry two copies of each gene. This raises questions about what tests Liliane has a lot to be grateful for this holiday season. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site. The extents to which intracellular and/or extracellular insults contribute to pathology remain an open question. Bone. doi: 10.1038/nmeth.2890, 22. Copyright 2023 NORD National Organization for Rare Disorders, Inc. All rights reserved. Prenatal clinical manifestations in individuals with COL4A1/2 variants. . https://www.ncbi.nlm.nih.gov/pubmed/20558831, Alamowitch S, Plaisier E, Favrole P, et al. Figure 3. Cavalin M, Mine M, Philbert M, et al. Oct;152A(10):2550-5. doi: 10.1002/ajmg.a.33659. and transmitted securely. This report highlights both the broad spectrum of COL4A1 mutations and the yield of testing the COL4A1 gene in familial ophthalmological and brain disorders. mutations: a novel genetic multisystem disease. functional hemispherectomy. Mosaicism can contribute to both reduced penetrance or variable expressivity but other factors do as well. doi: 10.1186/s12881-014-0097-2, 11. 2017 Jan;66:100-103. doi: 10.1016/j.pediatrneurol.2016.04.010. Slavotinek AM, Garcia ST, Chandratillake G, Bardakjian T, Ullah E, Wu D, et al. Basement membranes without these networks are unstable, leading to weakening of the tissues that they surround. MedlinePlus also links to health information from non-government Web sites. The COL4A1 stroke syndrome. 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. 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. Please enable it to take advantage of the complete set of features! Because the collagen is found throughout the body, COL4A1/A2 affects many organ systems, including the brain, kidneys, eyes, and muscles. Copyright 2023 by Gould Syndrome Foundation -. In most people, small vessel disease in the brain does not cause symptoms. In the human genome, there are 46 chromosomes. 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. Mutated patients develop a diffuse small vessel disease of the brain as shown by a diffuse leukoencephalopathy on MRI. Arch Neurol. We connect and coordinate our families with researchers and medical professionals to get our disease and management coordination into the medical realm. This blood vessel abnormality can cause episodes of bleeding within the eyes following any minor trauma to the eyes, leading to temporary vision loss. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3459649/, Federico A, Di Donato I, Bianchi S, et al. doi: 10.1001/archneur.1983.04050080067013, 17. To date, over 50 pathogenic or likely pathogenic variants have been described in the COL4A1 gene, most of them missense (2). Mutations in the gene have been linked to diseases of the brain, muscle, kidney, eye, and cardiovascular system. He was confident this would reduce or stop the This study clearly demonstrates that COL4A1 and COL4A2 mutations cause clinically variable cerebrovascular disease that includes characteristic features of cerebral small vessel disease. In a retrospective study of 52 patients with COL4A1 mutations, stroke occurred in 17.3% of subjects and MRI showed white matter abnormalities (63.5%), subcortical microbleeds (52.9%), porencephaly (46%), enlarged spaces around blood vessels, (19.2%), and small infarctions (13.5%). NORD is a registered 501(c)(3) charity organization. We therefore began our analysis of mutant Col4a1 G498V mice by examining the retinal vascular network at three and nine months of age. official website and that any information you provide is encrypted Jeanne M, Gould DB. 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. The ultimate goal of IAMRARE is to unite patients and research communities in the improvement of care and drug development. This condition causes mutations in genes that produce a specific type of collagen. Basement membranes without these networks are unstable, leading to weakening of the tissues that they surround. (2005) 308:116771. Individuals with COL4A1/A2-related disorders have characteristic patterns of brain disease when viewed under advanced imaging techniques. Systemic work-up including renal function, CK levels, urinary sediment test, and renal ultrasound proved unremarkable. Phone: 203-263-9938 National Library of Medicine By continuing to use this website, you agree to the Terms of Service & Privacy Policy. Autosomal Dominant Familial Porencephaly Type I. doi: 10.1212/WNL.0000000000001309, 8. If either parent also carries the mutation, it is considered inherited. 2009 Jun 25 [Updated 2016 Jul 7]. COL4A1/A2-related disorders follow an autosomal dominant pattern of inheritance. Bethesda, MD 20894, Web Policies (2004) 62:16135. IV-6 was born at 35 weeks after a pregnancy marked by gestational diabetes. (2010). 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. Together, these studies suggest that certain unknown variants of COL4A1 and COL4A2 might contribute to chronic vascular dysfunction. doi: 10.1111/cge.12379, 13. Stroke. (No doctor had ever taken a call on their lunch break to speak with me). Front. Thats not to say Zeeva hasnt had to work hard since the surgery. The risk of passing the non-working gene from an affected parent to an offspring is 50% for each pregnancy. Surgery may be necessary for individuals with severe cataracts. The human phenotypes are extremely variable between patients and between families, with disease onset as early as in the fetal period. Rarely, new mutations in the gene occur in people with no history of the disorder in their family. Stroke is a leading cause of death and serious long-term disability in developed nations. (2017) 377:111931. Interpretation of variant significance was done according to the American College of Medical Genetics and Genomics (ACMG) standards and guidelines (20). 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. 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. Further refinement of COL4A1 and COL4A2 related cortical malformations. Stay Informed With NORDs Email Newsletter, Launching Registries & Natural History Studies. Am J Neuroradiol. 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 Supporting children in their development to reduce handicaps and combining their follow-up with parent counseling could be considered as an ideal approach. When these ropes are secreted, they assemble into net-like structures outside the cells. In addition to providing strength and support to tissues, basement membranes provide instructional cues to cells. Affected individuals may also experience seizures and migraine headaches accompanied by visual sensations known as auras. Antiinflammatory therapy with canakinumab for atherosclerotic disease. 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. Background: COL4A1 mutations cause familial porencephaly, infantile hemiplegia, cerebral small vessel disease (CSVD), and hemorrhagic stroke. In some people, serious, life-threatening complications may occur in infancy; in others, only minor complications may occur and intelligence is unaffected. In cases where the mutation is inherited, the carrier parent is often clinically unaffected. Hum Mol Genet. (2008) 23:17. Gould Syndrome Foundation (COL4a1/COL4A2) seeks to educate the community on the rare disease COL4A1 and it's subcategorical diagnosis'. This can occur if the carrier is a mosaic which means that some cells carry the mutation while other cells do not. 10.1161/STROKEAHA.110.581918. 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. Thirdly, bioinformatic tools and ACMG (20) classify p.Gly743Val as likely pathogenic due to the combination of the following criteria: (i) the p.Gly743Val variant is located in a mutational hotspot/or critical and well-established functional domain, (ii) the p.Gly743Val variant is absent from controls in the Exome Sequencing Project as reported by GeneDx (30), (iii) the p.Gly743Val variant is a gene that has a low rate of benign missense variation and in which missense variants are a common mechanism of disease, (iv) the variant p.Gly743Val has been previously reported, without phenotypic description in one other report [GeneDx Accession: SCV000531635.4 Submitted: (January 29, 2019)] and from one likely pathogenic [Undiagnosed Diseases Network, NIH Accession: SCV000926981.1 Submitted: (February 21, 2019)], and (v) which multiple lines of computational evidence support a deleterious effect on the gene product (see the Bioinfromatic Interpretation of Results). Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/. The expanding phenotype of COL4A1 and COL4A2 mutations: clinical data on 13 newly identified families and a review of the literature. 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. doi: 10.1001/archophthalmol.2010.42, 10. [Hereditary angiopathy with nephropathy, aneurysms and muscle cramps (HANAC): a new basement membrane-disease associated with mutations of the COL4A1 gene]. 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. Science. Exome sequencing in 32 patients with anophthalmia/microphthalmia and developmental eye defects. Rannikme K, Davies G, Thomson PA, Bevan S, Devan WJ, Falcone GJ, et al. (2007) 357:268795. National Center for Biotechnology Information. The heterozygous variant c.2228G>T [NM_001845.4(COL4A1):c.2228G>T (p.Gly743Val)] was identified in exon 30 of the COL4A1 gene. 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. Phone: 617-249-7300, Danbury, CT office Collagen type IV alpha 1 (COL4A1) and 2 (COL4A2) are extracellular matrix proteins that together constitute a major component of nearly all basement membranes. Copyright 2023 NORD National Organization for Rare Disorders, Inc. All rights reserved. Understanding what it has taken to get her to this point, though, is close to unimaginable. (2014) 15:16. doi: 10.1038/gim.2014.210, 3. Fax: 203-263-9938, Washington, DC Office Gould Syndrome is diagnosed following a genetic test revealing a mutation in COL4A1 or COL4A2. Careers. ClinVar; [VCV000389182.3]. eCollection 2022. Received: 06 January 2020; Accepted: 01 July 2020; Published: 11 September 2020. Suite 500 cuts under the microscope. The conditions in this group have a range of signs and symptoms that involve fragile blood vessels. N Engl J Med. COL4A1/COL4A2 gene mutations description, symptoms and the sub-diagnosis. IV-5 had microcephaly without motor deficits, a language delay, a mental retardation (IQ of 62) that required adapted schooling, and severe hypermetropia. There are 28 different types of collagen in your body and mutations in the genes that encode these proteins lead to multiple, highly diverse diseases. Drugs that prevent irregular heartbeats (anti-arrhythmic medications) are used to treat supraventricular arrythmia. Suggestive evidence for linkage to chromosome 13qter for autosomal dominant type 1 porencephaly. We provide education, advocacy, and resources for families and individuals affected. Washington, DC 20036 doi: 10.1212/WNL.0b013e3181c3fd12, 9. 1779 Massachusetts Avenue Suite 310 In the human genome, there are 46 chromosomes. Molecular analysis was performed on a gDNA level by means of PCR amplification of all the coding exons and the flanking intron region. Aguglia U, Gambardella A, Breedveld GJ, Oliveri RL, Le Piane E, Messina D, et al. Cereb Circ Cogn Behav. Ensuring that patients and caregivers are armed with the tools they need to live their best lives while managing their rare condition is a vital part of NORDs mission. In most cases, an affected person has one parent with the condition. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.). 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). COL4A1-related brain small-vessel disease is characterized by weakening of the blood vessels in the brain. Collagen alpha-1(IV) chain (COL4A1) is a protein that in humans is encoded by the COL4A1 gene on chromosome 13. Another limitation is the systemic work-up based on described phenotypes and supposed affected organs. HHS Vulnerability Disclosure, Help At 1 month of age, a neuropediatric examination disclosed normal neck muscle tonus, normal Moro reflex, bilateral placing reaction, and open hands. Genet Med. The severity of the condition varies greatly among affected individuals. This analysis represents a subanalysis of the 35 out of 60 children <=18 years of age who reported a history of seizures. People listened to us and to Zeeva in a very different and proactive way. (2008) 17:42433. Plaisier E, Ronco P. COL4A1-Related Disorders. Molecular Dynamics Investigation on the Effects of Protonation and Lysyl Hydroxylation on Sulfilimine Cross-links in Collagen IV. Abnormal retinal arteries are prone to rupture causing bleeding associated with temporary loss of vision or even retinal detachments that can cause permanent vision loss. 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 COL4A1 and COL4A2 mutations and disease: insights into pathogenic mechanisms and potential therapeutic targets. 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. Symptoms that may occur in individuals with autosomal dominant type I porencephaly include migraines, weakness or paralysis of one side of the body (hemiparesis or hemiplegia), seizures, stroke, and dystonia, a group of neurological disorders characterized by involuntary muscle contractions that force the body into abnormal, sometimes painful, movements and positions. Neurology. ACS Omega. In addition to porencephaly there can be other forms of damage to the brain present at birth. 13 and so Gould Syndrome is considered Autosomal and should affect males and females in equal numbers. Aneurysms are bulges or enlargements of a blood vessel caused by weakening of the wall of the blood vessel. 2022 Oct 26;7(44):39680-39689. doi: 10.1021/acsomega.2c03360. Plaisier E, Chen Z, Gekeler F, Benhassine S, Dahan K, Marro B, Alamowitch S, 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). Seattle, WA: University of Washington, Seattle; 1993-. 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.