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Washington, DC 20036 Acute or chronic IOP elevation can lead to glaucoma where the increased pressure damages the optic nerve causing progressive and irreversible vision loss. COL4A1 Mutation in a Neonate With Intrauterine Stroke and Anterior Segment Dysgenesis. Gould Syndrome Foundation (COL4a1/COL4A2) - NORD (National Organization 2022 Sep;269(9):5153-5156. doi: 10.1007/s00415-022-11111-0. Type IV collagen is an important component of basement membranes in many tissues, especially blood vessels 1-6. (2002) 112:198202. Mutations in COL4A3, COL4A4 and COL4A5 were found in the early 1990's in patients with Alport Syndrome. doi: 10.1002/ana.23736, 4. Mutations in the gene have been linked to diseases of the brain, muscle, kidney, eye, and cardiovascular system. Ann (2015) 88:46873. and transmitted securely. 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. Seattle, WA: University of Washington, Seattle; 1993-. Systemic work-up including renal function, CK levels, urinary sediment test, and renal ultrasound proved unremarkable. Six alpha chains of type IV. Individuals with HANAC syndrome also experience a variety of eye problems. Antiinflammatory therapy with canakinumab for atherosclerotic disease. 2014 Mar;261(3):500-3. doi: 10.1007/s00415-013-7224-4. Molecular Dynamics Investigation on the Effects of Protonation and Lysyl Hydroxylation on Sulfilimine Cross-links in Collagen IV. Yet, five siblings, showing mild phenotype even in the second generation support a Mendelian transmission with variable expressivity and no other mechanism. Breedveld G, De Coo IF, Lequin MH, Arts WFM, Heutink P, Gould DB, et al. An official website of the United States government. COL4A1 mutations in patients with sporadic late-onset intracerebral It is not uncommon for an unaffected parent to have a severely affected child. Migraines can occur with or without aura. Acute urinary retention due to a novel collagen COL4A1 mutation. To use the sharing features on this page, please enable JavaScript. (1982) 40:5679. In addition to porencephaly there can be other forms of damage to the brain present at birth. 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). 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). What are the different ways a genetic condition can be inherited? doi: 10.1111/cge.12379, 13. 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 ( 2 - 4 ), hemorrhage ( 2, 5 - 7) and aneurysms ( 8 )], ophthalmological Genet Med. A novel COL4A1 gene mutation results in autosomal dominant non-syndromic congenital cataract in a Chinese family. A dominantly inherited mutation in collagen IV A1 (COL4A1) causing childhood onset stroke without porencephaly. Ultrasound in utero from IV-6 (A). Federal government websites often end in .gov or .mil. doi: 10.1007/s10897-008-9169-9, 16. eCollection 2021. 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. For asymptomatic patients, cerebral and vessel imaging for aneurysm screening and ophthalmologic follow-up are indicated (2). Axenfeld-Rieger anomaly involves underdevelopment and eventual tearing of the colored part of the eye (iris) and a pupil that is not in the center of the eye. IV-6 was born at 35 weeks after a pregnancy marked by gestational diabetes. Lenses corrected for hypermetropia. 10.1161/STROKEAHA.110.581918. 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. 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. doi: 10.1212/WNL.0b013e3181eee440, 28. Additionally, consultation with a genetic counselor is strongly recommended for affected individuals and their families and psychosocial support for the entire family is essential. However, these findings can be observed independently or in combinations, in many patients with COL4A1 and COL4A2 mutations. Aura refers to additional neurological symptoms that occur with, or sometimes before, the development of the migraine headache. Molecular analysis was performed on a gDNA level by means of PCR amplification of all the coding exons and the flanking intron region. Exon mutations of the COL4A1 genes are responsible for a broad spectrum of cerebral, ocular, and systemic manifestations. Ophthalmological features associated with COL4A1 mutations. Developmental defects to the front of the eye, which also includes the ocular drainage structures between the iris and cornea, can lead to increased pressure in the eye (elevated intraocular pressure, or IOP). Image showed ventricular asymmetry and brain MRI confirmed right frontotemporal dilatation (B). Neurology. Powered by NORD, the IAMRARE Registry Platform is driving transformative change in the study of rare disease. If neither parent carries the mutation, it is considered de novo which means that the mutation is a new occurrence. Surgery may be necessary for individuals with severe cataracts. Ann Neurol. Background: COL4A1 mutations cause familial porencephaly, infantile hemiplegia, cerebral small vessel disease (CSVD), and hemorrhagic stroke. 2009;73:1873-1882. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2881859/, Mao, M, Alavi MV, Labelle-Dumais, C, Gould DB. This blood vessel abnormality can cause episodes of bleeding within the eyes following any minor trauma to the eyes, leading to temporary vision loss. 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. Some individuals with COL4A1-related brain small-vessel disease do not have any signs or symptoms of the condition. January 31, 2019 We connect and coordinate our families with researchers and medical professionals to get our disease and management coordination into the medical realm. Cerebral small vessel disease with hemorrhage is likely milder continuum from porencephaly and exhibits many of the same symptoms (with the exception of the brain cavities). mutations: a novel genetic multisystem disease. It affects mainly young adults, children and more typically neonates. People listened to us and to Zeeva in a very different and proactive way. Neuropsychological tests disclosed language delay and learning difficulties requiring speech therapy at the age of 9 years. Recent findings: Quincy, MA 02169 These proteins have very restricted expression and Alport Syndrome primarily affects the kidneys with variable involvement of the eye and cochlea (hearing). 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 provides instructions for making one component of a protein called type IV collagen. Still other individuals may not develop any symptoms until well into adulthood. 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. 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. Cysts can also form in one or both kidneys, and the cysts may grow larger over time. At least 50 individuals with this condition have been described in the scientific literature. Finding the best care for Zeeva - Boston Children's Answers Rare disorders often go misdiagnosed or undiagnosed, making it difficult to determine their true frequency in the general population. Curr Med Chem. The size and location of cerebral cavities contributes to clinical variability. Role of COL4A1 in small-vessel disease and hemorrhagic stroke. Hereditary angiopathy with nephropathy, aneurysms, and muscle cramps (HANAC) syndrome is part of a group of conditions called the COL4A1-related disorders. Col4a1 mutation generates vascular abnormalities correlated with COL4A1/A2-Related Disorders - Symptoms, Causes, Treatment | NORD Feb;24(1):63-8. doi: 10.1097/WCO.0b013e32834232c6. 2013;73:48-57. https://www.ncbi.nlm.nih.gov/pubmed/23225343, Kuo DS, Labelle-Dumais C, Gould DB. 2017 Jan;66:100-103. doi: 10.1016/j.pediatrneurol.2016.04.010. Cavalin M, Mine M, Philbert M, et al. Mutations in Col4a1 cause perinatal cerebral hemorrhage and porencephaly. Understanding what it has taken to get her to this point, though, is close to unimaginable. Suggestive evidence for linkage to chromosome 13qter for autosomal dominant type 1 porencephaly. For example, the position of the mutation along the length of the protein can influence the severity of cerebrovascular disease and mutations in functional subdomains can influence the likelihood of tissue-specific involvement (for example, muscle). Resource(s) for Medical Professionals and Scientists on This Disease: 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). Neurology. This is called genotype-phenotype correlation. COL4A1/A2-related disorders are rare, genetic, multi-system disorders. J Perinatol. With genetic disorders, the type of mutation, or its location in the gene can sometimes be associated with varying outcomes. mutation in Axenfeld-Rieger anomaly with leukoencephalopathy and stroke. The expanding phenotype of COL4A1 and COL4A2 mutations: clinical data on 13 newly identified families and review of the literature. Some of these patients have been described as having HANAC syndrome, which is an acronym for hereditary angiopathy, nephropathy, aneurysms, and muscle cramps. 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. NORD strives to open new assistance programs as funding allows. doi: 10.1007/s00417-014-2800-6, 12. 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. COL4A1 Mutations as a Monogenic Cause of Cerebral Small Vessel - Stroke Rannikme K, Davies G, Thomson PA, Bevan S, Devan WJ, Falcone GJ, et al. U.S. Department of Health and Human Services, Autosomal dominant familial hematuria, retinal arteriolar tortuosity, contractures, Hereditary angiopathy with nephropathy, aneurysm, and muscle cramps syndrome. The https:// ensures that you are connecting to the 2012;54:569-574. https://www.ncbi.nlm.nih.gov/pubmed/22574627, Lanfranconi S, Markus HS. basement membranes surrounding the body's blood vessels, Genetic Testing Registry: Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps, National Organization for Rare Disorders (NORD), ANGIOPATHY, HEREDITARY, WITH NEPHROPATHY, ANEURYSMS, AND MUSCLE CRAMPS. Washington, DC 20036 The severity of the condition varies greatly among affected individuals. Available at: https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Cephalic-Disorders-Fact-Sheet Accessed January 28, 2019. 13 and so Gould Syndrome is considered Autosomal and should affect males and females in equal numbers. 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.