COL4A1 mutations cause progressive retinal neovascular defects and retinopathy. Neurology. doi: 10.1016/j.ejpn.2009.04.010, 27. (For more information on this disorder, choose cadasil as your search term in the Rare Disease Database.
(2009) 73:187382. COL4A1/A2-related disorders can also be associated with a variety of abnormalities affecting the front or back of the eyes. At least 50 individuals with this condition have been described in the scientific literature. 2010 Oct;152A(10):2550-5. doi: 10.1002/ajmg.a.33659. 2014 Mar;261(3):500-3. doi: 10.1007/s00415-013-7224-4. Gunda B, Mine M, Kovcs T, Hornyk C, Bereczki D, Vrallyay G, Rudas G, Audrezet MP, Tournier-Lasserve E. J Neurol. Feb;24(1):63-8. doi: 10.1097/WCO.0b013e32834232c6. Genotype-phenotype correlations in pathology caused by collagen type IV alpha 1 and 2 mutations. III-3 was asymptomatic but for severe hypermetropia and bilateral cataracts. It looks like nothing was found at this location. National Center for Biotechnology Information. Vahedi K, Alamowitch S. Clinical spectrum of type IV collagen (COL4A1) Received: 06 January 2020; Accepted: 01 July 2020; Published: 11 September 2020. . Hereditary angiopathy with nephropathy, aneurysms, and muscle cramps (HANAC) syndrome is part of a group of conditions called the COL4A1 -related disorders. Additionally, consultation with a genetic counselor is strongly recommended for affected individuals and their families and psychosocial support for the entire family is essential. Ronco P. Cerebrovascular disease related to COL4A1 mutations in HANAC syndrome. Stroke is a leading cause of death and serious long-term disability in developed nations. 1A-B). 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. The management of COL4A1/A2-related disorders may require the coordinated efforts of a team of specialists. Urine analysis to test for blood or excess protein can be used to evaluate renal function and identify if the kidneys might be affected. January 31, 2019 (2006) 354:148996. 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. (2008) 23:17. For asymptomatic patients, cerebral and vessel imaging for aneurysm screening and ophthalmologic follow-up are indicated (2). Suite 500 Dominant genetic disorders occur when only a single copy of a non-working gene is necessary to cause a particular disease. Still other individuals may not develop any symptoms until well into adulthood. The COL4A1 gene has 52 exons and most of the pathogenic variants are distributed across exons 10 to 47 in the triple-helix domain. Mice with Col4a1 and Col4a2 gene mutations have pathology in many organs and the presence and severity of pathology in a given organ appears to depend on the location of the mutation, genetic context, and environmental interactions. It affects mainly young adults, children and more typically neonates. doi: 10.1186/s12881-014-0097-2, 11. Clinically, COL4A1 mutations are responsible for different overlapping phenotypes including porencephaly (24), brain small vessel disease (2, 57) with or without ocular anomalies, HANAC (13) (hereditary angiopathy with nephropathy, aneurysms, and muscle cramps) syndrome, ophthalmological abnormalities (912), and non-syndromic autosomal dominant congenital cataracts (10). Neurology. COL4A1 Syndrome CADASIL The expressivity of the disease is highly variable with high intra- and inter-familial variability (2). doi: 10.1212/WNL.0000000000001309, 8. No patient had cramps, cardiac symptoms, or abnormalities or Raynaud phenomenon. Therapies are based on the specific symptoms in each individual. 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
Practical approach to the diagnosis of adult-onset - BMJ One patient (IV-3) was treated for spasticity and seizures with valproic acid. When we didnt feel we had any options left for treatment, People with HANAC syndrome develop kidney disease (nephropathy). Oral expression was reduced and neuropsychological testing revealed language delay with a prominent expression deficit. Changing lives of those with rare disease. COL4A1/A2-related disorders follow an autosomal dominant pattern of inheritance. Role of COL4A1 in basement-membrane integrity and cerebral small-vessel disease. Systemic work-up including renal function, CK levels, urinary sediment test, and renal ultrasound proved unremarkable. 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. Figure 3. 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). 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 . The COL4A1 and COL4A2 genes were screened in proband IV-6. HANAC syndrome is a rare condition, although the exact prevalence is unknown. The inheritance pattern is autosomal dominant (14) and age-dependent with almost 100% penetrance. The retina was collected and immunolabeled with an anti-collagen IV antibody, for reconstruction of the entire vascular network (Fig. Accessibility Washington, DC 20036 Treatment
Orphanet: HANAC syndrome Image showed ventricular asymmetry and brain MRI confirmed right frontotemporal dilatation (B). Molecular analysis was performed on a gDNA level by means of PCR amplification of all the coding exons and the flanking intron region. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). Comparison of Clinical, Radiographic, and Histological Features in COL4A1 Syndrome Compared With Other Single Gene Disorders Causing SVD. 30. How are genetic conditions treated or managed? Axenfeld-Rieger anomaly and cataract can cause impaired vision. We recently described hereditary angiopathy with nephropathy, aneurysm, and muscle cramps (HANAC) syndrome in 3 families with closely localized COL4A1 mutations. Available at: https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Cephalic-Disorders-Fact-Sheet Accessed January 28, 2019. 1779 Massachusetts Avenue Oct;152A(10):2550-5. doi: 10.1002/ajmg.a.33659. HHS Vulnerability Disclosure, Help Curr Med Chem. 2018;61:765-772. Basement membranes without these networks are unstable, leading to weakening of the tissues that they surround. 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). Front Aging Neurosci. Teaching families how to advocate for their loved ones and access medical information. (2015) 17:40524. Focke JK, Veltkamp R, Bauer P, Kraemer M. J Neurol. View CNBC interview with NORDs Peter Saltonstall and Boston Childrens Dr. Olaf Bodamer emphasizing the importance of investment in rare diseases. 2010 Prenatal clinical manifestations in individuals with COL4A1/2 variants. Our experience with Boston Childrens was very different from the other places we had been for epilepsy and neurology treatment. The effects of the disorder range from subtle or mild to severe, depending on associated brain abnormalities. However, in people with HANAC syndrome, these aneurysms typically do not burst.
Hereditary angiopathy with nephropathy, aneurysms, and - MedlinePlus Arterial retinal tortuosity can cause episodes of bleeding within the eye following any minor trauma to the eye, leading to temporary vision loss. 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. Mutations in COL4A3, COL4A4 and COL4A5 were found in the early 1990's in patients with Alport Syndrome. (1987) 8:4216. How can gene variants affect health and development? The expanding phenotype of COL4A1 and COL4A2 mutations: clinical data on 13 newly identified families and review of the literature. The strengths of our study are the extensive systemic work-up, the 5-year neurological follow-up, and the pluridisciplinary approach. Cerebrovascular disease related to COL4A1 mutations in HANAC syndrome. Aneurysms are bulges or enlargements of a blood vessel caused by weakening of the wall of the blood vessel. The https:// ensures that you are connecting to the Clin Neurol Neurosurg. 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. Born at term after a 39-week pregnancy, IV-3 had an unremarkable first clinical evaluation at 3 months.
What does it mean to have a COL4A1 - Little Braveheart | Facebook IV-3 and IV-6 are closely followed by a neuropediatrician (VW). Type IV collagen molecules attach to each other to form complex protein networks. Since fewer than 100 families have been reported, the exact prevalence of COL4A1-related disorders is not well-established. U.S. Department of Health and Human Services, Brain small-vessel disease with hemorrhage. 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. These aneurysms have the potential to burst, causing bleeding within the brain (hemorrhagic stroke). PS: wrote thi paper and performed the review of the literature under the supervision of GN. Participants with epilepsy frequently reported developmental delays (88.6%), stroke (60.0%), cerebral palsy (65.7%), and constipation (57.1%). It is important to discuss these concepts with a genetic counselor and understand their implications. In her first six years of life, Zeeva spent hundreds of nights in the hospital, had 13 operations and countless procedures, (from eye surgeries to Achilles heel, a shunt placed in her brain, and spine surgery). 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.