The COL4A1 gene provides instructions for making one component of a protein called type IV collagen. Epub 2016 Apr 24. Cerebrovascular disease related to COL4A1 mutations in HANAC syndrome Danbury, CT 06810 But she is learning to read, enjoys swimming, horseback riding, and is a glass jewelry and pottery artist. Together, these studies suggest that certain unknown variants of COL4A1 and COL4A2 might contribute to chronic vascular dysfunction. If we dont have a program for you now, please continue to check back with us. Neurol. cuts under the microscope. Epub 2010 Jun 17. One patient (IV-3) was treated for spasticity and seizures with valproic acid. Firstly, it segregates within the family with the phenotype. Phone: 203-263-9938 Additionally, consultation with a genetic counselor is strongly recommended for affected individuals and their families and psychosocial support for the entire family is essential. Stroke is often the first symptom of this condition, typically occurring in mid-adulthood. 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. 2022 Oct 26;7(44):39680-39689. doi: 10.1021/acsomega.2c03360. NORD is a registered 501(c)(3) charity organization. 1 Survivors often have a severely diminished quality of life, require long-term care, and are at high risk . Born at term after a 39-week pregnancy, IV-3 had an unremarkable first clinical evaluation at 3 months. Genotype-phenotype correlations in pathology caused by collagen type IV alpha 1 and 2 mutations. The COL4A1 stroke syndrome. Genet Med. COL4A1 is an essential component for basal membrane stability. There is in addition a specific phenotype called HANAC with constant nephropathy, muscle cramps and frequent intracranial aneurysms. Common variation in COL4A1/COL4A2 is associated with sporadic cerebral small vessel disease. Mutations in the COL4A1 gene cause HANAC syndrome. Participants with epilepsy frequently reported developmental delays (88.6%), stroke (60.0%), cerebral palsy (65.7%), and constipation (57.1%). (No doctor had ever taken a call on their lunch break to speak with me). doi: 10.1212/01.WNL.0000123113.46672.68, 25. The size and location of cerebral cavities contributes to clinical variability. The strengths of our study are the extensive systemic work-up, the 5-year neurological follow-up, and the pluridisciplinary approach. 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. PMC 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). 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. Gunda B, Mine M, Kovcs T, Hornyk C, Bereczki D, Vrallyay G, Rudas G, Audrezet MP, Tournier-Lasserve E. J Neurol. mutations: a novel genetic multisystem disease. Affected individuals may also experience seizures and migraine headaches accompanied by visual sensations known as auras. This raises questions about what tests Liliane has a lot to be grateful for this holiday season. Aicardi-Goutieres syndrome - About the Disease - Genetic and Rare The disorder causes many symptoms, not the least of which are strokes and epilepsy. How can gene variants affect health and development? (2002) 112:198202. (2015) 17:40524. 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. doi: 10.1212/WNL.0b013e3181eee440, 28. Glaucoma is initially treated with topical medications and, if medical therapy is unsuccessful, surgery. Neurologic phenotypes associated with COL4A1/2 mutations: expanding the spectrum of disease. (2010). 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. Doctors and researchers to bring research and medical therapeutic options to those affected. How are genetic conditions treated or managed? However, in people with HANAC syndrome, these aneurysms typically do not burst. This study clearly demonstrates that COL4A1 and COL4A2 mutations cause clinically variable cerebrovascular disease that includes characteristic features of cerebral small vessel disease. doi: 10.1126/science.1109418, 5. Childhood presentation of COL4A1 mutations. (2013) 73:4857. Interestingly, COL4A1 and COL4A2 mutations appear to lead to generally similar outcomes although COL4A2 mutations occur less frequently. small vessel disease: a systematic review. She, then, developed seizures which were controlled by valproic acid. Received: 06 January 2020; Accepted: 01 July 2020; Published: 11 September 2020. Dev Med Child Neurol. 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. Quincy, MA 02169 Internet. Phone: 203-263-9938 Plaisier E, Gribouval O, Alamowitch S, Mougenot B, Prost C, Verpont MC, et al. doi: However, these findings can be observed independently or in combinations, in many patients with COL4A1 and COL4A2 mutations. (2006) 354:148996. Affected infants and children can exhibit delays in reaching developmental milestones and varying degrees of intellectual disability. Some affected individuals may develop weakness or paralysis of one side of the body (hemiparesis or hemiplegia) and have seizures. 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. This can occur if the carrier is a mosaic which means that some cells carry the mutation while other cells do not. (2015) 84:91826. The limitations include the limited number of tested members (only two generations) due to a large family spread over Europe and not fully accessible. We each inherit a full complement on autosomes from each of our parents giving us two copies of each gene. (2014) 83:122834. COL4A2 mutation causing adult onset recurrent intracerebral hemorrhage and leukoencephalopathy. Vermeulen RJ, Peeters-Scholte C, Van Vugt JJMG, Barkhof F, Rizzu P, Van der Schoor SRD, et al. Therapies are based on the specific symptoms in each individual. Services that may be beneficial for some affected individuals include medical, social, and/or vocational services such as special remedial education. Pediatr Neurol. What does it mean if a disorder seems to run in my family? Various muscles can be affected and muscle strength can become weakened. 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. Resource(s) for Medical Professionals and Scientists on This Disease: (D) III- 3Brain MRI showed small asymptomatic lesions in white matter. MedlinePlus links to health information from the National Institutes of Health and other federal government agencies. HANAC syndrome is characterized by angiopathy, which is a disorder of the blood vessels. September 2003. 2021 Sep 10;13:727590. doi: 10.3389/fnagi.2021.727590. He also wanted to remove a shunt that was implanted in Most individuals diagnosed with a COL4A1-related disorder have an affected parent. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3459649/, Federico A, Di Donato I, Bianchi S, et al. (2004) 62:16135. 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. Neurology. Washington, DC 20036 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 N Engl J Med. Please note that NORD provides this information for the benefit of the rare disease community. Congenital Cephalic Disorders It is ubiquitously expressed in many tissues and cell types. This first-of-its-kind assistance program is designed for caregivers of a child or adult diagnosed with a rare disorder. Before Bennett RL, French KS, Resta RG, Doyle DL. A dominantly inherited mutation in collagen IV A1 (COL4A1) causing childhood onset stroke without porencephaly. Suite 310 The disorder causes many symptoms, not the least of which are strokes and epilepsy. 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. Mutated patients develop a diffuse small vessel disease of the brain as shown by a diffuse leukoencephalopathy on MRI. percent confident in Dr. Madsen and the epilepsy team. This site needs JavaScript to work properly. Axenfeld-Rieger anomaly and cataract can cause impaired vision. This is not specific to COL4A1/A2-related disorders, and is a sign of many different types of muscle disease. https://www.ncbi.nlm.nih.gov/pubmed/20558831, Alamowitch S, Plaisier E, Favrole P, et al. When our 8-year-old daughter, Zeeva, giggles and runs in her walker to the swing set, its like watching pure childhood joy. For asymptomatic patients, cerebral and vessel imaging for aneurysm screening and ophthalmologic follow-up are indicated (2). She had seizures every day, couldnt gain weight, sleep right, or generally enjoy her life. The cells of the retina trigger nerve impulses that run from the optic nerve to the brain to form sight. Contact a health care provider if you have questions about your health. (2007) 357:268795. Zeevas brain to treat a cyst in her brain caused by porencephaly. Neuropediatrics. Shah S, Ellard S, Kneen R, Lim M, Osborne N, Rankin J, et al. IV-3 had a left hemisphere porencephalic cyst and the lack of evidence of a left corticospinal tract on tractography (Figures 3E,F), IV-5 had a porencephalic cyst on the right lateral ventricle (Figure 3C), and III-3 had leukoencephalopathy (Figure 3D). GeneReviews. Matrix Biol. 55 Kenosia Avenue Front. (2014) 15:16. In addition to the effects of a clear COL4A1 or COL4A2 mutation, large genetic studies reported associations for COL4A1/A2 with intracranial aneurysms, myocardial infarction, arterial calcification, arterial stiffness, deep intracerebral hemorrhages, lacunar ischemic stroke, reduced white matter volume and vascular leukoencephalopathy. Disease Overview. 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. Supporting children in their development to reduce handicaps and combining their follow-up with parent counseling could be considered as an ideal approach. The surgery 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. Pathology. Neurology. Since fewer than 100 families have been reported, the exact prevalence of COL4A1-related disorders is not well-established. If individuals have muscle cramps, blood tests can reveal elevated levels creatine kinase, which is a muscle enzyme. 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. (1982) 40:5679. Aura refers to additional neurological symptoms that occur with, or sometimes before, the development of the migraine headache.

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