Next generation sequencing uncovers a missense mutation in COL4A1 as the cause of familial retinal arteriolar tortuosity. In her first six years of life, Zeeva spent hundreds of nights in the hospital, had 13 operations and countless procedures, (from eye surgeries to Achilles heel, a shunt placed in her brain, and spine surgery). Neurol. Understanding what it has taken to get her to this point, though, is close to unimaginable. Colin E, Sentilhes L, Sarfati A, Mine M, Guichet A, Ploton C, et al. In most people, small vessel disease in the brain does not cause symptoms. Standardized human pedigree nomenclature: update and assessment of the recommendations of the National Society of Genetic Counselors. This is called genotype-phenotype correlation. At least 50 individuals with this condition have been described in the scientific literature. Epub 2014 Jan 5. Services that may be beneficial for some affected individuals include medical, social, and/or vocational services such as special remedial education. Dev Med Child Neurol. Yet, as for all COL4A1 mutations, no specific treatment is currently available, and, due to the variable penetrance, adapted follow-up is challenging. The conditions in this group have a range of signs and symptoms that involve fragile blood vessels. 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. A dashed arrow indicates secondary atrophy in the left cerebral peduncle. COL4A1/A2-related disorders follow an autosomal dominant pattern of inheritance. The COL4A1 gene has 52 exons and most of the pathogenic variants are distributed across exons 10 to 47 in the triple-helix domain. There is in addition a specific phenotype called HANAC with constant nephropathy, muscle cramps and frequent intracranial aneurysms. In the brain, intracerebral hemorrhage is the most frequent phenotype. Neurology. Available at: https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Cephalic-Disorders-Fact-Sheet Accessed January 28, 2019. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site. Neurology. The effects of the disorder range from subtle or mild to severe, depending on associated brain abnormalities. By continuing to use this website, you agree to the Terms of Service & Privacy Policy. People with HANAC syndrome develop kidney disease (nephropathy). To use the sharing features on this page, please enable JavaScript. 2010 Aug;41(8):e513-8. Aneurysms are bulges or enlargements of a blood vessel caused by weakening of the wall of the blood vessel. Exome sequencing in 32 patients with anophthalmia/microphthalmia and developmental eye defects. Hum Mol Genet. 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. In addition the whole spectrum of the phenotype is not yet known and there are many asymptomatic patients. Glaucoma is initially treated with topical medications and, if medical therapy is unsuccessful, surgery. The limitations include the limited number of tested members (only two generations) due to a large family spread over Europe and not fully accessible. The COL4A1 gene mutations that cause HANAC syndrome result in the production of a protein that disrupts the structure of type IV collagen. Drugs that prevent irregular heartbeats (anti-arrhythmic medications) are used to treat supraventricular arrythmia. Mutations in Col4a1 cause perinatal cerebral hemorrhage and porencephaly. Feb;24(1):63-8. doi: 10.1097/WCO.0b013e32834232c6. 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. MedlinePlus links to health information from the National Institutes of Health and other federal government agencies. Eur J Paediatr Neurol. Curr Med Chem. Novel mutations in three families confirm a major role of COL4A1 in hereditary porencephaly. Genet Med. 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. J Perinatol. Genet Med. As a result, type IV collagen molecules cannot attach to each other to form the protein networks in basement membranes. The X and Y chromosomes are called the sex chromosomes and the rest all are called 'autosomes'. (D) III- 3Brain MRI showed small asymptomatic lesions in white matter. It is important to discuss these concepts with a genetic counselor and understand their implications. Zagaglia S, Selch C, Nisevic JR, Mei D, Michalak Z, Hernandez-Hernandez L, et al. Compared to other COL4A1-related disorders, the brain is only mildly affected in HANAC syndrome. Stroke. doi: 10.1007/s00417-014-2800-6, 12. Other eye problems associated with HANAC syndrome include a clouding of the lens of the eye (cataract) and an abnormality called Axenfeld-Rieger anomaly. Please note that NORD provides this information for the benefit of the rare disease community. Similar blood vessel weakness and breakage occurs in the eyes of some affected individuals. The disorder causes many symptoms, not the least of which are strokes and epilepsy. 2021 Sep 10;13:727590. doi: 10.3389/fnagi.2021.727590. 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. doi: 10.1016/j.matbio.2016.10.003, 23. Lecordier S, Manrique-Castano D, El Moghrabi Y, ElAli A. Fax: 203-263-9938, Washington, DC Office Clinical case reports suggest a syndrome with characteristic core findings; however, much about the disorder is not fully understood. What are the different ways a genetic condition can be inherited? (2018) 91:e207888. (2011) 42:13. A diagnosis can be confirmed through molecular genetic testing. This raises questions about what tests Liliane has a lot to be grateful for this holiday season. An official website of the United States government. Painful muscle cramps can occur and can develop before three years of age. 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. His bedside manner was incredible. The variability and severity of symptoms is significant and how COL4A1/A2-related disorders will potentially affect an individual can be unique. 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. In: Pagon RA, Bird TD, Dolan CR, et al., GeneReviews. Careers. J Genet Couns. 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. The proportion of cases caused by a de novopathogenic variant is estimated to be at least 27%. The information on this site should not be used as a substitute for professional medical care or advice. Novel heterozygous COL4A2 variant c.2572A>G, p.(I858V) mimicking Sneddon's and Divry van Bogaert Syndrome. This report highlights both the broad spectrum of COL4A1 mutations and the yield of testing the COL4A1 gene in familial ophthalmological and brain disorders. Neurology. Contact a health care provider if you have questions about your health. 2010;17(13):1317-24. doi: Other phenotypes include intracranial aneurysms, porencephaly, infantile hemiparesis, muscle cramps, optic nerve dysgenesis and secondary glaucoma. 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 severity of the condition varies greatly among affected individuals. Clin Neurol Neurosurg. 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. These protein networks are the main components of basement membranes, which are thin sheet-like structures that separate and support cells in many tissues. MedlinePlus also links to health information from non-government Web sites. 1900 Crown Colony Drive 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. In people with HANAC syndrome, the vasculature and other tissues within the kidneys, brain, muscles, eyes, and throughout the body weaken. Going from having seizures every day for six years to having no seizures is nothing short of a miracle. 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. Each child of an individual with a COL4A1-related disorder has a 50% chance of inheriting the pathogenic variant. 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). Summary: Available at: https://www.ncbi.nlm.nih.gov/books/NBK7046/ Accessed January 28, 2019. However, in people with HANAC syndrome, these aneurysms typically do not burst. J Neurol Sci. I cannot describe the feeling of seeing your child healed. 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. Some individuals with COL4A1-related brain small-vessel disease do not have any signs or symptoms of the condition. The COL4A2 test was negative. Suite 310 The timeline for the clinical examination and ancillary tests performed is illustrated in Figure 2. Image showed ventricular asymmetry and brain MRI confirmed right frontotemporal dilatation (B). IV-3 was diagnosed with ventriculomegaly in utero. Phone: 203-263-9938 Please enable it to take advantage of the complete set of features! The X and Y chromosomes are called the sex chromosomes and the rest all are called 'autosomes'. Individuals with high blood pressure (hypertension) must receive appropriate therapy because of the increased risk of stroke. Childhood presentation of COL4A1 mutations. ClinVar; [VCV000389182.3]. Gould Syndrome is an ultra rare genetic, multi-system disorder. Advanced imaging techniques can include computerized tomography (CT) scanning and magnetic resonance imaging (MRI). Nearly half of these participants were diagnosed with infantile spasms. Some affected individuals may develop weakness or paralysis of one side of the body (hemiparesis or hemiplegia) and have seizures. 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. 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. The risk of passing the non-working gene from an affected parent to an offspring is 50% for each pregnancy. https://www.clinicaltrialsregister.eu/, JOURNAL ARTICLES Copyright 2023 by Gould Syndrome Foundation -, https://rarediseases.org/rare-diseases/col4a1-a2-related-disorders/. 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. However, in rare pathologies with few cases, we may have missed undescribed or subclinical manifestations. We connect and coordinate our families with researchers and medical professionals to get our disease and management coordination into the medical realm. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3459649/, Federico A, Di Donato I, Bianchi S, et al. Neurologic phenotypes associated with COL4A1/2 mutations: expanding the spectrum of disease. COL4A1/A2-related disorders can also be associated with a variety of abnormalities affecting the front or back of the eyes. This first-of-its-kind assistance program is designed for caregivers of a child or adult diagnosed with a rare disorder. 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. 13 and so Gould Syndrome is considered Autosomal and should affect males and females in equal numbers. The first time he came to meet us, Zeeva threw a sock at him. Summary. These protein networks are the main component of basement membranes, which are thin sheet-like structures that separate and support cells in many tissues. doi: 10.1002/ajmg.10452, 18. Seattle, WA: University of Washington, Seattle; 1993-. Other causes of porencephaly were ruled out [maternal alloimmunization, trauma, peri-natal cerebral ischemia (normal Apgar scores at birth), and negative TORCH complex tests]. Firstly, it segregates within the family with the phenotype. Eur J Med Genet. The COL4A1 gene provides instructions for making one component of a protein called type IV collagen. 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. Plaisier E, Gribouval O, Alamowitch S, Mougenot B, Prost C, Verpont MC, et al. She had seizures every day, couldnt gain weight, sleep right, or generally enjoy her life. The expanding phenotype of COL4A1 and COL4A2 mutations: clinical data on 13 newly identified families and a review of the literature. In people with HANAC syndrome, angiopathy affects several parts of the body. doi: 10.1136/jmg.2005.035584, 15. Alamowitch S, Plaisier E, Favrole P, Prost C, Chen Z, Van Agtmael T, Marro B, COL4A1/A2-related disorders are believed to affect females and males in equal numbers. Copyright 2023 NORD National Organization for Rare Disorders, Inc. All rights reserved. Curr Opin Neurol. (For more information on this disorder, choose cadasil as your search term in the Rare Disease Database. Since fewer than 100 families have been reported, the exact prevalence of COL4A1-related disorders is not well-established. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Type IV Collagens and Basement Membrane Diseases: Cell Biology and Pathogenic Mechanisms. Surgery may be necessary for individuals with severe cataracts. 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). 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: 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. Collagen alpha-1(IV) chain (COL4A1) is a protein that in humans is encoded by the COL4A1 gene on chromosome 13. Sci Rep. 2016;6:18602. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728690/, Rannikmae K, Davies G, Thomson PA, et al. Cerebrovascular disease related to COL4A1 mutations in HANAC syndrome. 2013;73:48-57. https://www.ncbi.nlm.nih.gov/pubmed/23225343, Kuo DS, Labelle-Dumais C, Gould DB. Aura refers to additional neurological symptoms that occur with, or sometimes before, the development of the migraine headache. 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. It affects mainly young adults, children and more typically neonates. How can gene variants affect health and development? In: Adam MP, Everman DB, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. COL4A1 and COL4A2 are on Chr. IV-3 goes to a normal school, but special schooling is required for IV-6. COL4A1/A2-related disorders are caused by dominant mutations in the COL4A1 or COL4A2 genes. 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. Plaisier E, Chen Z, Gekeler F, Benhassine S, Dahan K, Marro B, Alamowitch S, Paques M, Ronco P. Am J Med Genet A. Affected infants and children can exhibit delays in reaching developmental milestones and varying degrees of intellectual disability. Rare disorders often go misdiagnosed or undiagnosed, making it difficult to determine their true frequency in the general population. Hereditary angiopathy with nephropathy, aneurysms, and muscle cramps (HANAC) syndrome is part of a group of conditions called the COL4A1 -related disorders. (2008) 23:17. We therefore began our analysis of mutant Col4a1 G498V mice by examining the retinal vascular network at three and nine months of age. 2018;61:765-772. Acute urinary retention due to a novel collagen COL4A1 mutation. . The disorder causes many symptoms, not the least of which are strokes and epilepsy. mutations: a novel genetic multisystem disease. PV and VW followed the children at the Neuropediatrics clinic of the same hospital. 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). Washington, DC 20036 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. Curr Opin Neurol. Neurology. See our, COL4A1-related brain small-vessel disease, URL of this page: https://medlineplus.gov/genetics/condition/col4a1-related-brain-small-vessel-disease/. Ophthalmological features associated with COL4A1 mutations. 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). This page is currently unavailable. Surgery or endovascular therapy can be used to treat intracranial hemorrhage. came with risks and was the hardest decision we had ever faced, yet we felt 100 Years published: 2019. Your support helps to ensure everyones free access to NORDs rare disease reports. He underwent at birth neurosonography for axial hypotonia that revealed ventricular asymmetry and right frontotemporal dilatation (Figure 3). Role of COL4A1 in small-vessel disease and hemorrhagic stroke. Danbury, CT 06810 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). HANAC syndrome is characterized by angiopathy, which is a disorder of the blood vessels. Am J Med Genet. COL4A1 disorder is probably largely underestimated because of its multisystem and variable phenotype. Staals J, Makin SDJ, Doubal FN, Dennis MS, Wardlaw JM. IV-5Brain MRI revealing porencephalic cyst of frontal horn of lateral right ventricle (C). Am J Neuroradiol. Meuwissen MEC, Halley DJJ, Smit LS, Lequin MH, Cobben JM, De Coo R, et al. A novel COL4A1 gene mutation results in autosomal dominant non-syndromic congenital cataract in a Chinese family. Epub 2016 Apr 24. In the human genome, there are 46 chromosomes. (2012) 54:56974. During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of certain tissue structures. doi: 10.1016/j.ejpn.2009.04.010, 27. Zeevas brain to treat a cyst in her brain caused by porencephaly. Cerebrovascular disease related to COL4A1 mutations in HANAC syndrome. 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. Porencephaly refers to the formation of fluid-filled cysts or cavities within of the brain. 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. Gould DB, Phalan FC, van Mil SE, Sundberg JP, Vahedi K, Massin P, et al. Mutations in COL4A3, COL4A4 and COL4A5 were found in the early 1990's in patients with Alport Syndrome. The .gov means its official. PMC 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. 1A-B). 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). Disclaimer. doi: 10.1001/archneur.1983.04050080067013, 17. doi: 10.1038/gim.2015.30, 21. Cysts can also form in one or both kidneys, and the cysts may grow larger over time. Phone: 202-588-5700. 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: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282239/. 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. PS: wrote thi paper and performed the review of the literature under the supervision of GN. COL4A1 may be a candidate gene in unexplained familial syndromes with autosomal dominant hematuria, cystic kidney disease, intracranial aneurysms, and muscle cramps. Aicardi-Goutieres syndrome - About the Disease - Genetic and Rare Diseases Information Center National Center for Advancing Translational Sciences Browse by Disease About GARD Contact Us We recently launched the new GARD website and are still developing specific pages. Quincy, MA 02169 Ten months later, the left hemiparesis was observed with a lack of voluntary prehension on his left side without spasticity. Neurology. Phenotypic spectrum of COL4A1 mutations: porencephaly to schizencephaly. Before Email: [emailprotected], Some current clinical trials also are posted on the following page on the NORD website: NORD is a registered 501(c)(3) charity organization. 10.1161/STROKEAHA.110.581918. The COL4A1 and COL4A2 genes were screened in proband IV-6. Neurovascular Alterations in Vascular Dementia: Emphasis on Risk Factors. National Library of Medicine Gunda B, Mine M, Kovcs T, Hornyk C, Bereczki D, Vrallyay G, Rudas G, Audrezet MP, Tournier-Lasserve E. J Neurol. PS and NL: followed III-3 at the Erasme Neurology outpatients clinic. (2014) 15:16. The information on this site should not be used as a substitute for professional medical care or advice. (2015) 88:46873. Unauthorized use of these marks is strictly prohibited. What are the different ways a genetic condition can be inherited? COL4A1/A2-related disorders are rare, genetic, multi-system disorders. for the triple helical CB3[IV] domain. Bookshelf Progressive cerebral atrophies in three children with COL4A1 mutations. Collagen type IV alpha 1 (COL4A1) and 2 (COL4A2) are extracellular matrix proteins that together constitute a major component of nearly all basement membranes. COL4A1 mutations and hereditary angiopathy, nephropathy, aneurysms, and muscle cramps. 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. 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. At 1 month of age, a neuropediatric examination disclosed normal neck muscle tonus, normal Moro reflex, bilateral placing reaction, and open hands. To date, over 50 pathogenic or likely pathogenic variants have been described in the COL4A1 gene, most of them missense (2). 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. 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 . Vilain C, Van Regemorter N, Verloes A, David P, Van Bogaert P. Neuroimaging fails to identify asymptomatic carriers of familial porencephaly. 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. It looks like nothing was found at this location. Pathology. In the brain, intracerebral hemorrhage is the most frequent phenotype. Cataracts, which are a clouding of the lenses of the eyes, are often present from birth (congenital) and may be one of the first identifiable signs of the syndrome. cutting tissue called the corpus callosum, then make some additional delicate U.S. Department of Health and Human Services, Brain small-vessel disease with hemorrhage. Standardized (15) familiar pedigree is showed in Figure 1. 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. 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. 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. (2015) 17:84353. Thats not to say Zeeva hasnt had to work hard since the surgery. Type IV collagen molecules attach to each other to form complex protein networks. Am J Med Genet A. (2009) 73:187382. If individuals have muscle cramps, blood tests can reveal elevated levels creatine kinase, which is a muscle enzyme. 2022 Sep;269(9):5153-5156. doi: 10.1007/s00415-022-11111-0. (2010) 75:7479. N Engl J Med. 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.