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. As a result, type IV collagen molecules cannot attach to each other to form the protein networks in basement membranes. Phone: 617-249-7300, Danbury, CT office The conditions in this group have a range of signs and symptoms that involve fragile blood vessels. Genet Med. There are no standardized treatment protocols or guidelines for affected individuals. These protein networks are the main components of basement membranes, which are thin sheet-like structures that separate and support cells in many tissues. 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. Depending on the cell type that acquires the mutation and when the mutation arises, the individual may have many or few cells with the mutation. Vermeulen RJ, Peeters-Scholte C, Van Vugt JJMG, Barkhof F, Rizzu P, Van der Schoor SRD, et al. Unauthorized use of these marks is strictly prohibited. In most people, small vessel disease in the brain does not cause symptoms. Here we report a family in which three siblings presented severe hypermetropia and porencephaly. Curr Opin Neurol. (D) III- 3Brain MRI showed small asymptomatic lesions in white matter. 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. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). 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). Stroke is a leading cause of death and serious long-term disability in developed nations. 8600 Rockville Pike Neurologic phenotypes associated with COL4A1/2 mutations: expanding the spectrum of disease. Zeevas brain to treat a cyst in her brain caused by porencephaly. 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. 2022 Sep;269(9):5153-5156. doi: 10.1007/s00415-022-11111-0. HANAC syndrome is characterized by angiopathy, which is a disorder of the blood vessels. III-3 was informed of the genetic diagnosis and is now regularly followed and screened for cataracts and brain aneurysms. What are the different ways a genetic condition can be inherited? 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. NORD and MedicAlert Foundation have teamed up on a new program to provide protection to rare disease patients in emergency situations. These genes are the blueprints for two proteins that wind together like a long rope inside cells. Secondly, the p.Gly743Val variant is a missense mutation that shares features with other missense pathogenic mutations that occur in the COL4A1 gene exon 30: congenital porencephaly, epilepsy, and neuropsychological anomalies in p.Gly749Ser (23, 24), ophthalmologic defects and neuropsychological deficits in absence of systemic signs in variant p.Gly755Arg (2527), and antenatal fetal intracerebral hemorrhage, ocular anomalies associated to cerebral leukoencephalopathy in variant p.Gly773Arg (12, 28, 29). Childhood presentation of COL4A1 mutations. PS and NL: followed III-3 at the Erasme Neurology outpatients clinic. At least six affected families have been described in the scientific literature. He underwent at birth neurosonography for axial hypotonia that revealed ventricular asymmetry and right frontotemporal dilatation (Figure 3). Another limitation is the systemic work-up based on described phenotypes and supposed affected organs. cutting tissue called the corpus callosum, then make some additional delicate (2006) 354:148996. Yoneda Y, Haginoya K, Kato M, Osaka H, Yokochi K, Arai H, et al. Probands' father had severe hypermetropia and bilateral cataracts. (2002) 112:198202. 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. mutations: a novel genetic multisystem disease. (2015) 88:46873. How can gene variants affect health and development? for the triple helical CB3[IV] domain. mutations: a novel genetic multisystem disease. But she is learning to read, enjoys swimming, horseback riding, and is a glass jewelry and pottery artist. U.S. Department of Health and Human Services, Brain small-vessel disease with hemorrhage. The information on this site should not be used as a substitute for professional medical care or advice. More info about Gould Syndrome is available at https://rarediseases.org/rare-diseases/col4a1-a2-related-disorders/. We provide education, advocacy, and resources for families and individuals affected. In the eye, patients may have retinal arteriolar tortuosities and retinal hemorrhages or anterior segment dysgenesis. Washington, DC 20036 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). doi: 10.1007/s10897-008-9169-9, 16. The conditions in this group have a range of signs and symptoms that involve fragile blood vessels. During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of certain tissue structures. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3459649/, Federico A, Di Donato I, Bianchi S, et al. Neurology. Internet. Congenital Cephalic Disorders It looks like nothing was found at this location. Suite 500 The first time he came to meet us, Zeeva threw a sock at him. Comparison of Clinical, Radiographic, and Histological Features in COL4A1 Syndrome Compared With Other Single Gene Disorders Causing SVD. 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 the structure of the brain (cerebral cortical abnormalities) and lung (pulmonary) abnormalities continue to emerge and the full spectrum is still uncharacterized. The conditions in this group have a range of signs and symptoms that involve fragile blood vessels. The two genes that code for these proteins are tightly linked on chromosome 13 and dominant COL4A1 and COL4A2 gene mutations cause a highly variable, multisystem disorder. For the nucleotide numbering, the HVGS terms (www.hgvs.org) were applied with the nucleotide A of the ATG startcodon = c.1. Plaisier E, Ronco P. COL4A1-Related Disorders. NORD strives to open new assistance programs as funding allows. These proteins have very restricted expression and Alport Syndrome primarily affects the kidneys with variable involvement of the eye and cochlea (hearing). How can gene variants affect health and development? Affected individuals may also experience seizures and migraine headaches accompanied by visual sensations known as auras. Gould Syndrome is an ultra rare genetic, multi-system disorder. COL4A1 and COL4A2 mutations and disease: insights into pathogenic mechanisms and potential therapeutic targets. Curr Med Chem. Individuals with COL4A1/A2-related disorders have characteristic patterns of brain disease when viewed under advanced imaging techniques. Meuwissen MEC, Halley DJJ, Smit LS, Lequin MH, Cobben JM, De Coo R, et al. Pediatr Neurol. Stroke. Together, these studies suggest that certain unknown variants of COL4A1 and COL4A2 might contribute to chronic vascular dysfunction. I cannot describe the feeling of seeing your child healed. We each inherit a full complement on autosomes from each of our parents giving us two copies of each gene. 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. N Engl J Med. Aguglia U, Gambardella A, Breedveld GJ, Oliveri RL, Le Piane E, Messina D, et al. Image showed ventricular asymmetry and brain MRI confirmed right frontotemporal dilatation (B). 55 Kenosia Avenue Please note that NORD provides this information for the benefit of the rare disease community. *Correspondence: Pasquale Scoppettuolo, Pasquale.scoppettuolo@gmail.com, https://www.ncbi.nlm.nih.gov/clinvar/variation/VCV000389182.3, Creative Commons Attribution License (CC BY). Phone: 617-249-7300, Danbury, CT office HANAC syndrome is caused by genetic changes in the COL4A1 gene. 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. The COL4A1 stroke syndrome. 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. GeneReviews. TTY: (866) 411-1010 (E,F) IV-3Brain MRI showed left frontotemporal dilatation and diffusion tensor imaging (DTI) sequences demonstrated no left corticospinal tract (cranio-caudal fibers, indigo, with arrows). doi: 10.1186/s12881-014-0097-2, 11. sharing sensitive information, make sure youre on a federal Some affected individuals may develop weakness or paralysis of one side of the body (hemiparesis or hemiplegia) and have seizures. Facebook: https://www.facebook.com/Col4A1Foundation Please Note This page is currently unavailable. Clin Neurol Neurosurg. (2014) 34:757. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). (2015) 17:40524. Gould Syndrome is a rare, genetic, multi-system disorder. 2008 May;192(5):971-84; discussion 984-6. J Neurol Sci. His bedside manner was incredible. (2005) 308:116771. No use, distribution or reproduction is permitted which does not comply with these terms. 2022 Mar 24;3:100140. doi: 10.1016/j.cccb.2022.100140.
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