We recently described hereditary angiopathy with nephropathy, aneurysm, and muscle cramps (HANAC) syndrome in 3 families with closely localized COL4A1 mutations. Porencephaly refers to the formation of fluid-filled cysts or cavities within of the brain. Fax: 203-263-9938, Washington, DC Office Zenteno JC, Cresp J, Buentello-Volante B, Buil JA, Bassaganyas F, Vela-Segarra JI, et al. The brain MRI of IV-6 disclosed a large right-sided frontoparietal cavity (Figure 3B) with communication to the lateral ventricle, isosignal to CFS. Ultrasound in utero from IV-6 (A). Our review highlights that COL4A1 mutations can present for the first time in adult life with features of cerebral SVD, including subcortical hemorrhage and ischemic stroke, . Summary. Bethesda, MD 20894, Web Policies (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.). Vahedi K, Alamowitch S. Clinical spectrum of type IV collagen (COL4A1) 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. Neurol. 2021 Sep 10;13:727590. doi: 10.3389/fnagi.2021.727590. Available online at: https://www.ncbi.nlm.nih.gov/clinvar/variation/VCV000389182.3 (accessed March 20, 2020). III-3 was informed of the genetic diagnosis and is now regularly followed and screened for cataracts and brain aneurysms. 2017;155:45-57. https://www.ncbi.nlm.nih.gov/pubmed/28254515, Alavi MV, Mao M, Pawlikowski BT, et al. Phone: 617-249-7300, Danbury, CT office 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. 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. About half of people with this condition 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). Comparison of Clinical, Radiographic, and Histological Features in COL4A1 Syndrome Compared With Other Single Gene Disorders Causing SVD. https://www.ncbi.nlm.nih.gov/pubmed/20558831, Alamowitch S, Plaisier E, Favrole P, et al. 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. 2018;61:765-772. This is not specific to COL4A1/A2-related disorders, and is a sign of many different types of muscle disease. Supporting children in their development to reduce handicaps and combining their follow-up with parent counseling could be considered as an ideal approach. (2014) 34:757. In affected individuals, stroke is usually caused by bleeding in the brain (hemorrhagic stroke) rather than a lack of blood flow in the brain (ischemic stroke), although either type can occur. Paques M, Ronco P. Novel COL4A1 mutations associated with HANAC syndrome: a role 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. Understanding what it has taken to get her to this point, though, is close to unimaginable. Vahedi K, Alamowitch S. Clinical spectrum of type IV collagen (COL4A1) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3459649/, Federico A, Di Donato I, Bianchi S, et al. J Perinatol. Bennett RL, French KS, Resta RG, Doyle DL. (2018) 91:e207888. J Genet Couns. 10.1161/STROKEAHA.110.581918. Some individuals develop cysts on the kidney. She also showed severe hypermetropia. COL4A1 encodes type IV collagen 1 chain, a crucial component of nearly all basement membrane including vasculature, renal glomerule and ocular structures. MedlinePlus links to health information from the National Institutes of Health and other federal government agencies. Front. Clinical Testing and Workup The heterozygous variant c.2228G>T [NM_001845.4(COL4A1):c.2228G>T (p.Gly743Val)] was identified in exon 30 of the COL4A1 gene. The inheritance pattern is autosomal dominant (14) and age-dependent with almost 100% penetrance. Arterial retinal tortuosity can cause episodes of bleeding within the eye following any minor trauma to the eye, leading to temporary vision loss. 1779 Massachusetts Avenue Hereditary angiopathy with nephropathy, aneurysms, and - MedlinePlus COL4A1 mutations cause progressive retinal neovascular defects and retinopathy. As a result, type IV collagen molecules cannot attach to each other to form the protein networks in basement membranes. What does it mean to have a COL4A1 - Little Braveheart | Facebook 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). 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. Aneurysms are bulges or enlargements of a blood vessel caused by weakening of the wall of the blood vessel. 1 Survivors often have a severely diminished quality of life, require long-term care, and are at high risk . National Center for Biotechnology Information. No microbleeds or cystic cavities were found. Since fewer than 100 families have been reported, the exact prevalence of COL4A1-related disorders is not well-established. At 1 month of age, a neuropediatric examination disclosed normal neck muscle tonus, normal Moro reflex, bilateral placing reaction, and open hands. CADASIL patients can experience progressive memory loss, deterioration of intellectual abilities and loss of balance with a progressive worsening of these symptoms, but symptoms are usually less severe and occur later in life. Ronco P. Cerebrovascular disease related to COL4A1 mutations in HANAC syndrome. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282239/. Early intervention is important in ensuring that children with reach their highest potential. 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. Breedveld G, De Coo IF, Lequin MH, Arts WFM, Heutink P, Gould DB, et al. Clinical case reports suggest a syndrome with characteristic core findings; however, much about the disorder is not fully understood. IV-3 and IV-6 are closely followed by a neuropediatrician (VW). Axenfeld-Rieger anomaly is associated with various other eye abnormalities, including underdevelopment and eventual tearing of the colored part of the eye (iris), and a pupil that is not in the center of the eye. Bull Acad Natl Med. (2015) 88:46873. Fetal intracerebral hemorrhage and cataract: think COL4A1. Yet, five siblings, showing mild phenotype even in the second generation support a Mendelian transmission with variable expressivity and no other mechanism. doi: 10.1002/ana.23736, 4. doi: 10.1056/NEJMoa071906, 14. This group rarely survives beyond 2 years. In addition the whole spectrum of the phenotype is not yet known and there are many asymptomatic patients. (2012) 54:56974. Molecular Dynamics Investigation on the Effects of Protonation and Lysyl Hydroxylation on Sulfilimine Cross-links in Collagen IV. 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. Gould DB, Phalan FC, van Mil SE, Sundberg JP, Vahedi K, Massin P, et al. As a result, type IV collagen molecules cannot attach to each other to form the protein networks in basement membranes. Axenfeld-Rieger is a collection of abnormalities affecting the front of the eye including the iris (colored part of the eye) and cornea (abnormally small corneas called microcornea), which is the transparent membrane that covers the eyes. came with risks and was the hardest decision we had ever faced, yet we felt 100 We described the phenotype associated to a likely pathogenic variant of the COL4A1 gene (c.2228G>T, p.Gly743Val) responsible for severe hypermetropia and familial porencephaly. Yoneda Y, Haginoya K, Kato M, Osaka H, Yokochi K, Arai H, et al. Gould Syndrome is an ultra rare genetic, multi-system disorder. MedlinePlus also links to health information from non-government Web sites. COL4A1 -related brain small-vessel disease is characterized by weakening of the blood vessels in the brain. COL4A1 collagen type IV alpha 1 chain [ (human)] - National Center for January 31, 2019 2022 May 27;13:827165. doi: 10.3389/fneur.2022.827165. Any muscle may be affected, and cramps usually last from a few seconds to a few minutes, although in some cases they can last for several hours. The degree of mosaicism is highly variable ranging from only a small percent of cells with the mutation to nearly all cells carrying the mutation and depends on the stage during development that the mutation occurred. Meuwissen MEC, Halley DJJ, Smit LS, Lequin MH, Cobben JM, De Coo R, et al. Email: [emailprotected], Some current clinical trials also are posted on the following page on the NORD website: Urine analysis to test for blood or excess protein can be used to evaluate renal function and identify if the kidneys might be affected. 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). Role of COL4A1 in small-vessel disease and hemorrhagic stroke. Mutations in COL4A3, COL4A4 and COL4A5 were found in the early 1990's in patients with Alport Syndrome. 4 Both . The information on this site should not be used as a substitute for professional medical care or advice. Lanfranconi S, Markus HS. Gould DB, Phalan FC, Breedveld GJ, Van Mil SE, Smith RS, Schimenti JC, et al. Individuals with COL4A1/A2-related disorders have characteristic patterns of brain disease when viewed under advanced imaging techniques. This review dsecribes the clinical spectrum of a newly identified disorder related to COL4A1 gene mutations. COL4A1-related brain small-vessel disease is characterized by weakening of the blood vessels in the brain. Various muscles can be affected and muscle strength can become weakened. for the triple helical CB3[IV] domain. I cannot describe the feeling of seeing your child healed. 1900 Crown Colony Drive Arch Neurol. Common variation in COL4A1/COL4A2 is associated with sporadic cerebral small vessel disease. Compared to other COL4A1-related disorders, the brain is only mildly affected in HANAC syndrome. Here we report a family in which three siblings presented severe hypermetropia and porencephaly. Some individuals do not have any observable symptoms (asymptomatic); others can develop severe, even life-threatening complications. Nearly half of these participants were diagnosed with infantile spasms. doi: 10.1016/j.matbio.2016.10.003, 23. PS: wrote thi paper and performed the review of the literature under the supervision of GN. Standardized (15) familiar pedigree is showed in Figure 1. Internet. TTY: (866) 411-1010 One patient (IV-3) was treated for spasticity and seizures with valproic acid. See our, Hereditary angiopathy with nephropathy, aneurysms, and muscle cramps syndrome, URL of this page: https://medlineplus.gov/genetics/condition/hereditary-angiopathy-with-nephropathy-aneurysms-and-muscle-cramps-syndrome/. Participants with epilepsy frequently reported developmental delays (88.6%), stroke (60.0%), cerebral palsy (65.7%), and constipation (57.1%). This page is currently unavailable. COL4A1 brain small-vessel disease is an autosomal dominant condition resulting from a mutation to the COL4A1 gene, located on the long arm of chromosome 13, that normally encodes for the alpha-1 chain of type IV collagen 1-6. If neither parent carries the mutation, it is considered de novo which means that the mutation is a new occurrence. The COL4A2 test was negative. Fragile or damaged blood vessels or basement membranes in the kidneys can lead to blood in the urine (hematuria). (2007) 357:268795. Stay Informed With NORDs Email Newsletter, Launching Registries & Natural History Studies. Researchers are still trying to determine whether there are any specific genotype-phenotype correlations in COL4A1/A2-related disorders. View CNBC interview with NORDs Peter Saltonstall and Boston Childrens Dr. Olaf Bodamer emphasizing the importance of investment in rare diseases. COL4A1/A2-Related Disorders - Symptoms, Causes, Treatment | NORD However, in people with HANAC syndrome, these aneurysms typically do not burst. Doctors and researchers to bring research and medical therapeutic options to those affected. Is Robert Hamner Related To Earl Hamner, Sloth Experience London, Articles C
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