No use, distribution or reproduction is permitted which does not comply with these terms. Cysts can also form in one or both kidneys, and the cysts may grow larger over time. 2018;61:765-772. Going from having seizures every day for six years to having no seizures is nothing short of a miracle. The https:// ensures that you are connecting to the The main symptom is single or repeated bleeding inside the skull (intracranial hemorrhaging) that can occur without cause (spontaneously), after trauma, or when taking drugs that slow blood clotting (anticoagulants). One year later, right hemiparesis became clinically evident with a lack of right voluntary hand prehension in association with right hemineglect.
What is Gould Syndrome? - Gould Syndrome Foundation The networks formed by the COL4A1 and COL4A2 proteins are called basement membranes and are present in every organ of the body. Neuropediatrics. 2022 Sep;269(9):5153-5156. doi: 10.1007/s00415-022-11111-0. Zeeva woke up after a ten-hour procedure, opened her eyes, and it felt like we were seeing her for the first time. Abnormal blood vessels in the brain are a major consequence of COL4A1 and COL4A2 gene mutations. Rarely, new mutations in the gene occur in people with no history of the disorder in their family. 2008 May;192(5):971-84; discussion 984-6. IV-5 had microcephaly without motor deficits, a language delay, a mental retardation (IQ of 62) that required adapted schooling, and severe hypermetropia. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282239/. See our, COL4A1-related brain small-vessel disease, URL of this page: https://medlineplus.gov/genetics/condition/col4a1-related-brain-small-vessel-disease/. Early intervention is important in ensuring that children with reach their highest potential. This group rarely survives beyond 2 years. The effects of the disorder range from subtle or mild to severe, depending on associated brain abnormalities. 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. In the brain, intracerebral hemorrhage is the most frequent phenotype. Neurologic phenotypes associated with COL4A1/2 mutations: expanding the spectrum of disease. 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. 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 . 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.
COL4A1 Mutations as a Monogenic Cause of Cerebral Small Vessel - Stroke I cannot describe the feeling of seeing your child healed. Sci Rep. 2016;6:18602. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728690/, Rannikmae K, Davies G, Thomson PA, et al. Dr. Madsen suggested Zeeva have an operation called a 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 people, small vessel disease in the brain does not cause symptoms. COL4A1/COL4A2 gene mutations description, symptoms and the sub-diagnosis. The retina was collected and immunolabeled with an anti-collagen IV antibody, for reconstruction of the entire vascular network (Fig. (2007) 357:268795. At 1 month of age, a neuropediatric examination disclosed normal neck muscle tonus, normal Moro reflex, bilateral placing reaction, and open hands. (2006) 43:4905. With genetic disorders, the type of mutation, or its location in the gene can sometimes be associated with varying outcomes. NCI CPTC Antibody Characterization Program. Mutations in Col4a1 cause perinatal cerebral hemorrhage and porencephaly. Gould Syndrome is an ultra rare genetic, multi-system disorder. Gunda B, Mine M, Kovcs T, Hornyk C, Bereczki D, Vrallyay G, Rudas G, Audrezet MP, Tournier-Lasserve E. J Neurol. It affects mainly young adults, children and more typically neonates. Phenotypic spectrum of COL4A1 mutations: porencephaly to schizencephaly. Type IV Collagens and Basement Membrane Diseases: Cell Biology and Pathogenic Mechanisms. These exceptions are nuanced and should be discussed with a genetic counselor. In the human genome, there are 46 chromosomes. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. 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. doi: 10.1007/s10897-008-9169-9, 16.
COL4A1 Mutations Cause Neuromuscular Disease with - ScienceDirect cutting tissue called the corpus callosum, then make some additional delicate 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. Feb;24(1):63-8. doi: 10.1097/WCO.0b013e32834232c6. HANAC syndrome is a rare condition, although the exact prevalence is unknown. Yet, five siblings, showing mild phenotype even in the second generation support a Mendelian transmission with variable expressivity and no other mechanism. 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. Lenses corrected for hypermetropia. (2020). Curr Opin Neurol. ClinVar; [VCV000389182.3]. Pediatr Neurol. His bedside manner was incredible. 10.1161/STROKEAHA.110.581918. The risk is the same for males and females. Type IV collagen molecules attach to each other to form complex protein networks. The expanding phenotype of COL4A1 and COL4A2 mutations: clinical data on 13 newly identified families and review of the literature. Suite 310 Suggestive evidence for linkage to chromosome 13qter for autosomal dominant type 1 porencephaly. 2017;155:45-57. https://www.ncbi.nlm.nih.gov/pubmed/28254515, Alavi MV, Mao M, Pawlikowski BT, et al. Unauthorized use of these marks is strictly prohibited. COL4A1/A2-related disorders can also be associated with a variety of abnormalities affecting the front or back of the eyes. 1900 Crown Colony Drive 2011 In the brain, intracerebral hemorrhage is the most frequent phenotype. Maybe try a search? This page is currently unavailable. Molecular Dynamics Investigation on the Effects of Protonation and Lysyl Hydroxylation on Sulfilimine Cross-links in Collagen IV. 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. J Neurol Sci. In: Adam MP, Everman DB, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. Eur J Paediatr Neurol. Comparison of Clinical, Radiographic, and Histological Features in COL4A1 Syndrome Compared With Other Single Gene Disorders Causing SVD. Available at: https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Cephalic-Disorders-Fact-Sheet Accessed January 28, 2019. HANAC syndrome is characterized by angiopathy, which is a disorder of the blood vessels. Mutated patients develop a diffuse small vessel disease of the brain as shown by a diffuse leukoencephalopathy on MRI. 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. COL4A1 encodes type IV collagen 1 chain, a crucial component of nearly all basement membrane including vasculature, renal glomerule and ocular structures. Feb;24(1):63-8. doi: 10.1097/WCO.0b013e32834232c6. Please note that NORD provides this information for the benefit of the rare disease community. Copyright 2020 Scoppettuolo, Ligot, Wermenbol, Van Bogaert and Naeije. If we dont have a program for you now, please continue to check back with us. Ophthalmological features associated with COL4A1 mutations. Phone: 203-263-9938 These protein networks are the main component of basement membranes, which are thin sheet-like structures that separate and support cells in many tissues. Fazekas F, Chawluk JB, Alavi A. MR signal abnormalities at 1.5 T in Alzheimer's dementia and normal aging. Therefore, it is important to note that there is a very broad spectrum of clinical presentations with different organs affected to different degrees between patients. Resource(s) for Medical Professionals and Scientists on This Disease: He was confident this would reduce or stop the http://www.centerwatch.com/, For information about clinical trials conducted in Europe, contact: Hereditary angiopathy with nephropathy, aneurysms, and muscle cramps (HANAC) syndrome is part of a group of conditions called the COL4A1 -related disorders. Dr. Joseph Madsen was as wonderful in person as he had been on the phone. 2017 Jan;66:100-103. doi: 10.1016/j.pediatrneurol.2016.04.010. PS and NL: followed III-3 at the Erasme Neurology outpatients clinic. 2009 Dec 1;73(22):1873-82. doi: 10.1212/WNL.0b013e3181c3fd12. Individuals with this condition are at increased risk of having more than one stroke in their lifetime. Unable to load your collection due to an error, Unable to load your delegates due to an error. Arch Neurol. A variety of additional signs and symptoms have been reported in individuals with COL4A1/A2-related disorders including childhood-onset epilepsy, hemolytic anemia (a condition characterized by low levels of circulating red blood cells due to their premature destruction leading to fatigue, weakness, lightheadedness, dizziness, irritability, headaches, and pale skin color), mitral valve prolapse (flaps of the valve located between the upper and lower left heart chambers bulge or collapse during contraction allowing leakage of blood back into the left atrium). 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. Phone: 202-588-5700. Neurology. 2010 COL4A1/A2-related disorders are believed to affect females and males in equal numbers. Fetal origin of brain damage in 2 infants with a COL4A1 mutation: fetal and neonatal MRI. Copyright 2023 NORD National Organization for Rare Disorders, Inc. All rights reserved. This variant p.Gly743Val combines hypermetropia in all heterozygotic patients and highly penetrant antenatal porencephaly (associated with motor and intellectual deficits). 1. Brain magnetic resonance imaging (MRI) scans were carried out on a three Tesla Brain MRI (Achieva, Ingenia; Philips Healthcare, Best, The Netherlands). Disclaimer. COL4A1/A2-related disorders are caused by dominant mutations in the COL4A1 or COL4A2 genes. Other eye problems associated with HANAC syndrome include a clouding of the lens of the eye (cataract) and an abnormality called Axenfeld-Rieger anomaly. (2012) 54:56974. How can gene variants affect health and development? Type IV collagen molecules attach to each other to form complex protein networks. In the eye, patients may have retinal arteriolar tortuosities and retinal hemorrhages or anterior segment dysgenesis. The causative gene of HANAC is COL4A1 (13q34) encoding the alpha1 chain of collagen IV, a major component of basement membranes also involved in . Some individuals do not have any observable symptoms (asymptomatic); others can develop severe, even life-threatening complications. People with this condition may have a bulge in one or multiple blood vessels in the brain (intracranial aneurysms). He smiled, caught it, and asked Zeeva if he could throw it back. Muscle cramps experienced by most people with HANAC syndrome typically begin in early childhood. 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. Summary: Front. This condition causes mutations in genes that produce a specific type of collagen. Neurology. Here we report a family in which three siblings presented severe hypermetropia and porencephaly. 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.
Neurologic phenotypes associated with COL4A1/2 mutations MedlinePlus also links to health information from non-government Web sites. Dominant genetic disorders occur when only a single copy of a non-working gene is necessary to cause a particular disease. Paques M, Ronco P. Novel COL4A1 mutations associated with HANAC syndrome: a role Lanfranconi S, Markus HS. IV-6 was born at 35 weeks after a pregnancy marked by gestational diabetes. A novel COL4A1 gene mutation results in autosomal dominant non-syndromic congenital cataract in a Chinese family. 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.