col4a1 syndrome life expectancy

Matrix Biol. We connect and coordinate our families with researchers and medical professionals to get our disease and management coordination into the medical realm. Glaucoma is initially treated with topical medications and, if medical therapy is unsuccessful, surgery. COL4A1-related brain small-vessel disease is a rare condition, although the exact prevalence is unknown. COL4A1/A2-Related Disorders - Symptoms, Causes, Treatment | NORD (2014) 83:122834. No ophthalmological surgery was planned on annual control for any member, but only positive lens correction prescribed. Hereditary angiopathy with nephropathy, aneurysms, and muscle cramps (HANAC) syndrome is part of a group of conditions called the COL4A1-related disorders. In the human genome, there are 46 chromosomes. Ann Neurol. Ronco P. Cerebrovascular disease related to COL4A1 mutations in HANAC syndrome. No patient had cramps, cardiac symptoms, or abnormalities or Raynaud phenomenon. This report highlights both the broad spectrum of COL4A1 mutations and the yield of testing the COL4A1 gene in familial ophthalmological and brain disorders. The strengths of our study are the extensive systemic work-up, the 5-year neurological follow-up, and the pluridisciplinary approach. 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. Shah S, Ellard S, Kneen R, Lim M, Osborne N, Rankin J, et al. It is possible that insufficient collagen in the basement membrane predisposes blood vessels in the brain to leak or rupture. 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 (24), hemorrhage (2, 57) and aneurysms (8)], ophthalmological (912) (retinal artery tortuosity, Axenfeld Rieger anomalies, cataracts, and severe hypermetropia), renal (13) (renal cysts, and microscopic hematuria), and systemic (13) findings (cramps with a high creatine kinase level [CK], Raynaud's phenomenon, and arrhythmias). COL4A1 may be a candidate gene in unexplained familial syndromes with autosomal dominant hematuria, cystic kidney disease, intracranial aneurysms, and muscle cramps. Combinations of the in silico tool MutationTaster (21) and the Alamut software (ALAMUT package, http://www.interactivebiosoftware.com, France) predicted the variant to be pathogenic as it likely alters the protein structure/function due to a detrimental effect on 112 heterotrimers formation and type IV collagen stability. Lenses corrected for hypermetropia. At 1 month of age, a neuropediatric examination disclosed normal neck muscle tonus, normal Moro reflex, bilateral placing reaction, and open hands. Mutated patients develop a diffuse small vessel disease of the brain as shown by a diffuse leukoencephalopathy on MRI. Zagaglia Selch C, Nisevic JR, et al. Neurol. Systemic work-up including renal function, CK levels, urinary sediment test, and renal ultrasound proved unremarkable. Bennett RL, French KS, Resta RG, Doyle DL. The management of COL4A1/A2-related disorders may require the coordinated efforts of a team of specialists. Most individuals diagnosed with a COL4A1-related disorder have an affected parent. Some may only develop specific symptoms such as isolated migraines or strokes in childhood or adulthood. Volonghi I, Pezzini A, Del Zotto E, Giossi A, Costa P, Ferrari D, Padovani A. Therapies are based on the specific symptoms in each individual. Firstly, it segregates within the family with the phenotype. 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. Antiinflammatory therapy with canakinumab for atherosclerotic disease. HHS Vulnerability Disclosure, Help Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Stroke. Individuals with this condition are at increased risk of having more than one stroke in their lifetime. Other phenotypes include intracranial aneurysms, porencephaly, infantile hemiparesis, muscle cramps, optic nerve dysgenesis and secondary glaucoma. It is ubiquitously expressed in many tissues and cell types. doi: 10.1007/s00417-014-2800-6, 12. 2008 May;192(5):971-84; discussion 984-6. Lanfranconi S, Markus HS. Figure 3. COL4A1 Mutations Cause Neuromuscular Disease with - ScienceDirect Schwarz JM, Cooper DN, Schuelke M, Seelow D. Mutationtaster2: Mutation prediction for the deep-sequencing age. The conditions in this group have a range of signs and symptoms that involve fragile blood vessels. COL4A1/A2-related disorders follow an autosomal dominant pattern of inheritance. Available at: https://www.ncbi.nlm.nih.gov/books/NBK7046/ Accessed January 28, 2019. 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. Graefe's Arch Clin Exp Ophthalmol. Orphanet: HANAC syndrome Zagaglia S, Selch C, Nisevic JR, Mei D, Michalak Z, Hernandez-Hernandez L, et al. https://www.ncbi.nlm.nih.gov/pubmed/26610912. Cesarean delivery for pregnancies with fetus at risk for a COL4A1-related disorder is recommended to prevent brain vascular injury attributable to birth trauma during delivery (6). The .gov means its official. Many patients with COL4A1 and COL4A2 mutations have additional signs and symptoms that do not include the cerebral vasculature. The first time he came to meet us, Zeeva threw a sock at him. However, in people with HANAC syndrome, these aneurysms typically do not burst. INTERNET N Engl J Med. 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. Accessibility The cells of the retina trigger nerve impulses that run from the optic nerve to the brain to form sight. The COL4A1 gene mutations that cause HANAC syndrome result in the production of a protein that disrupts the structure of type IV collagen. I cannot describe the feeling of seeing your child healed. 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. 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. Muscle cramps experienced by most people with HANAC syndrome typically begin in early childhood. cutting tissue called the corpus callosum, then make some additional delicate (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.). NORD is a registered 501(c)(3) charity organization. sharing sensitive information, make sure youre on a federal (1982) 40:5679. 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. Pediatricians are physicians who specialize in the childhood disorders and are often the first to detect patients with COL4A1/A2-related disorders. The disorder causes many symptoms, not the least of which are strokes and epilepsy. Genotype-phenotype correlations in pathology caused by collagen type IV alpha 1 and 2 mutations. (19). 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. Neuropsychological tests disclosed language delay and learning difficulties requiring speech therapy at the age of 9 years. The size and location of cerebral cavities contributes to clinical variability. Jeanne M, Gould DB. 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. Email: [emailprotected], Some current clinical trials also are posted on the following page on the NORD website: The effects of the disorder range from subtle or mild to severe, depending on associated brain abnormalities. COL4A1 Syndrome CADASIL TTY: (866) 411-1010 2011 Phenotypic spectrum of COL4A1 mutations: porencephaly to schizencephaly. The expressivity of the disease is highly variable with high intra- and inter-familial variability (2). J Genet Couns. Suite 500 One patient (IV-3) was treated for spasticity and seizures with valproic acid. Treatment trials will be critical to determine the long-term safety and effectiveness of specific medications and treatments for individuals with COL4A1/A2-related disorders. 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. 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. COL4A1/A2-related disorders are rare, genetic, multi-system disorders. COL4A2 mutation causing adult onset recurrent intracerebral hemorrhage and leukoencephalopathy. Genet Med. Hereditary angiopathy with nephropathy, aneurysms, and - MedlinePlus All patients suffering from HANAC syndrome display retinal arteriolar tortuosity and occasional retinal hemorrhages. (2002) 112:198202. Oct;152A(10):2550-5. doi: 10.1002/ajmg.a.33659. COL4A1/COL4A2 gene mutations description, symptoms and the sub-diagnosis. To use the sharing features on this page, please enable JavaScript. In the human genome, there are 46 chromosomes. This variant p.Gly743Val combines hypermetropia in all heterozygotic patients and highly penetrant antenatal porencephaly (associated with motor and intellectual deficits). (D) III- 3Brain MRI showed small asymptomatic lesions in white matter. He also wanted to remove a shunt that was implanted in Abnormal blood vessels in the brain are a major consequence of COL4A1 and COL4A2 gene mutations. mutations: a novel genetic multisystem disease. 2017;155:45-57. https://www.ncbi.nlm.nih.gov/pubmed/28254515, Alavi MV, Mao M, Pawlikowski BT, et al. III-3 was informed of the genetic diagnosis and is now regularly followed and screened for cataracts and brain aneurysms. 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. Stay Informed With NORDs Email Newsletter, Launching Registries & Natural History Studies. 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. 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. 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. 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. Comparisons may be useful for a differential diagnosis: CADASIL is a rare genetic disorder affecting the small blood vessels in the brain. Gould Syndrome is an ultra rare genetic, multi-system disorder. More info about Gould Syndrome is available at https://rarediseases.org/rare-diseases/col4a1-a2-related-disorders/. 2022 Sep;269(9):5153-5156. doi: 10.1007/s00415-022-11111-0. NORD and MedicAlert Foundation have teamed up on a new program to provide protection to rare disease patients in emergency situations. 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. Am J Med Genet. Common variation in COL4A1/COL4A2 is associated with sporadic cerebral small vessel disease. 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. The extents to which intracellular and/or extracellular insults contribute to pathology remain an open question. With genetic disorders, the type of mutation, or its location in the gene can sometimes be associated with varying outcomes. Neurology. 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. COL4A1 mutations as a monogenic cause of cerebral small vessel disease: a systematic review. Hereditary angiopathy with nephropathy, aneurysms, and muscle cramps Surgery or endovascular therapy can be used to treat intracranial hemorrhage. In people with HANAC syndrome, the vasculature and other tissues within the kidneys, brain, muscles, eyes, and throughout the body weaken. Aura refers to additional neurological symptoms that occur with, or sometimes before, the development of the migraine headache. Front. 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. 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. September 2003. Epub 2014 Jan 5. Meuwissen MEC, Halley DJJ, Smit LS, Lequin MH, Cobben JM, De Coo R, et al. Contact a health care provider if you have questions about your health. 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). (2017) 5758:2944. Clipboard, Search History, and several other advanced features are temporarily unavailable. Prenatal clinical manifestations in individuals with COL4A1/2 variants. Am J Med Genet A. Agenesis of the Corpus Callosum | National Institute of Neurological Interestingly, COL4A1 and COL4A2 mutations appear to lead to generally similar outcomes although COL4A2 mutations occur less frequently. COL4A1 disorder is probably largely underestimated because of its multisystem and variable phenotype. Written informed consent was obtained from the patient and the patient's parents for publication of this case report. small vessel disease: a systematic review. People listened to us and to Zeeva in a very different and proactive way. 2015;17:843-853. https://www.nature.com/articles/gim2014210, Yoneda Y, Haginoya K, Kato M, et al. Stroke is a leading cause of death and serious long-term disability in developed nations. 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. In the front of the eye, patients can have abnormally small eyes (microphthalmia), cataracts (cloudy lenses), and anterior segment dysgenesis (Axenfeld-Rieger). COL4A1 -related brain small-vessel disease is characterized by weakening of the blood vessels in the brain. (2013) 73:4857. Together, these studies suggest that certain unknown variants of COL4A1 and COL4A2 might contribute to chronic vascular dysfunction. Genet Med. View CNBC interview with NORDs Peter Saltonstall and Boston Childrens Dr. Olaf Bodamer emphasizing the importance of investment in rare diseases. 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. 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. Liu X, Yang Q, Tang L, He J, Tian D, Wang B, Xie L, Li C, Fan D. Front Neurol. 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. (2010) 75:7479. Gould Syndrome is a rare, genetic, multi-system disorder. As a result, type IV collagen molecules cannot attach to each other to form the protein networks in basement membranes. Stay Informed With NORDs Email Newsletter, Launching Registries & Natural History Studies, https://nord1dev.wpengine.com/for-patients-and-families/information-resources/info-clinical-trials-and-research-studies/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282239/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5328961/, https://www.ncbi.nlm.nih.gov/pubmed/28254515, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728690/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4351667/, https://www.nature.com/articles/gim2014210, https://www.ncbi.nlm.nih.gov/pubmed/23225343, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3459649/, https://www.ncbi.nlm.nih.gov/pubmed/22868088, https://www.ncbi.nlm.nih.gov/pubmed/22574627, https://www.ncbi.nlm.nih.gov/pubmed/20558831, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2881859/, https://www.ncbi.nlm.nih.gov/pubmed/26610912, https://www.ncbi.nlm.nih.gov/books/NBK7046/, https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Cephalic-Disorders-Fact-Sheet, https://rarediseases.org/patient-assistance-programs/medicalert-assistance-program/, https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/, https://rarediseases.org/patient-assistance-programs/caregiver-respite/, Learn more about Patient Assistance Programs >, Arginine: Glycine Amidinotransferase Deficiency, https://rarediseases.org/non-member-patient/epilepsy-foundation/, Gould Syndrome Foundation (COL4a1/COL4A2), https://rarediseases.org/non-member-patient/gould-syndrome-foundation-col4a1-col4a2/, https://rarediseases.org/non-member-patient/national-kidney-foundation/, https://rarediseases.org/non-member-patient/nih-national-eye-institute/, NIH/National Institute of Neurological Disorders and Stroke, Aromatic L-Amino Acid Decarboxylase Deficiency, https://rarediseases.org/non-member-patient/nih-national-institute-of-neurological-disorders-and-stroke/, https://rarediseases.org/non-member-patient/the-arc/, Learn more about Patient Organization & Membership >, HANAC: hereditary angiopathy, nephropathy and cramps syndrome (OMIM #611773), POREN1: autosomal dominant type 1 porencephaly; porencephaly with infantile hemiplegia (OMIM #175780, RATOR: retinal arterial tortuosity (OMIM #180000), BSVD: brain small vessel disease with or without ocular anomalies (OMIM #607595), ICH: susceptibility to intracerebral hemorrhage (OMIM #614519). We each inherit a full complement on autosomes from each of our parents giving us two copies of each gene. (18) and Staals et al. 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. 2022 Mar 24;3:100140. doi: 10.1016/j.cccb.2022.100140. Brain magnetic resonance imaging (MRI) scans were carried out on a three Tesla Brain MRI (Achieva, Ingenia; Philips Healthcare, Best, The Netherlands). The X and Y chromosomes are called the sex chromosomes and the rest all are called 'autosomes'. 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. 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). Plaisier E, Chen Z, Gekeler F, Benhassine S, Dahan K, Marro B, Alamowitch S, Paques M, Ronco P. Am J Med Genet A. Thats not to say Zeeva hasnt had to work hard since the surgery. doi: 10.2214/ajr.149.2.351, 19. To date, over 50 pathogenic or likely pathogenic variants have been described in the COL4A1 gene, most of them missense (2). Zeeva woke up after a ten-hour procedure, opened her eyes, and it felt like we were seeing her for the first time. 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. Comparison of Clinical, Radiographic, and Histological Features in COL4A1 Syndrome Compared With Other Single Gene Disorders Causing SVD. She was struggling to advance both cognitively and physically because of uncontrolled epilepsy. Seattle, WA: University of Washington, Seattle; 1993-. MedlinePlus links to health information from the National Institutes of Health and other federal government agencies. 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. The timeline for the clinical examination and ancillary tests performed is illustrated in Figure 2. Bull Acad Natl Med. Coupry I, Sibon I, Mortemousque B, Rouanet F, Mine M GC. Gould DB, Phalan FC, van Mil SE, Sundberg JP, Vahedi K, Massin P, et al. The expanding phenotype of COL4A1 and COL4A2 mutations: clinical data on 13 newly identified families and a review of the literature. Painful muscle cramps can occur and can develop before three years of age. The retina was collected and immunolabeled with an anti-collagen IV antibody, for reconstruction of the entire vascular network (Fig. Copyright 2023 NORD National Organization for Rare Disorders, Inc. All rights reserved. Ultrasound in utero from IV-6 (A). The risk of passing the non-working gene from an affected parent to an offspring is 50% for each pregnancy. Breedveld G, De Coo IF, Lequin MH, Arts WFM, Heutink P, Gould DB, et al. Novel heterozygous COL4A2 variant c.2572A>G, p.(I858V) mimicking Sneddon's and Divry van Bogaert Syndrome. cuts under the microscope. This analysis represents a subanalysis of the 35 out of 60 children <=18 years of age who reported a history of seizures. Cereb Circ Cogn Behav. Smoking, which also increases the risk of stroke, physical activities that can cause head trauma such as contact sports, and the use of anti-clotting (anticoagulant) medications, should be avoided. Purpose of review: Exon mutations of the COL4A1 genes are responsible for a broad spectrum of cerebral, ocular, and systemic manifestations. Neurology. https://www.ncbi.nlm.nih.gov/pubmed/20558831, Alamowitch S, Plaisier E, Favrole P, et al. In addition to porencephaly there can be other forms of damage to the brain present at birth. In people with COL4A1-related brain small-vessel disease, the vasculature in the brain weakens, which can lead to blood vessel breakage and stroke. 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. (2020). Bone. doi: 10.1002/ajmg.10452, 18. Washington, DC 20036 2017 Jan;66:100-103. doi: 10.1016/j.pediatrneurol.2016.04.010. Muscle cramps can be spontaneous or triggered by exercise. Clin Genet. 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. This first-of-its-kind assistance program is designed for caregivers of a child or adult diagnosed with a rare disorder. What is the prognosis of a genetic condition? Dev Med Child Neurol. (2010) 14:1827. People with this condition may have a bulge in one or multiple blood vessels in the brain (intracranial aneurysms). Pediatr Neurol. Molecular Dynamics Investigation on the Effects of Protonation and Lysyl Hydroxylation on Sulfilimine Cross-links in Collagen IV. NORD is a registered 501(c)(3) charity organization. Available online at: https://www.ncbi.nlm.nih.gov/clinvar/variation/VCV000389182.3 (accessed March 20, 2020). Our experience with Boston Childrens was very different from the other places we had been for epilepsy and neurology treatment. She had seizures every day, couldnt gain weight, sleep right, or generally enjoy her life. This can manifest as porencephaly if the vessels rupture in utero, hemorrhagic stroke postnatally or in adults, or even small cerebral microbleeds that might go unnoticed except on MRI.