col4a1 syndrome life expectancy col4a1 syndrome life expectancy

doi: 10.1111/cge.12379, 13. Mutations in the COL4A1 gene cause HANAC syndrome. Please note that NORD provides this information for the benefit of the rare disease community. 1900 Crown Colony Drive Sci Rep. 2016;6:18602. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728690/, Rannikmae K, Davies G, Thomson PA, et al. Neurology. Paques M, Ronco P. Novel COL4A1 mutations associated with HANAC syndrome: a role Copyright 2023 by Gould Syndrome Foundation -, https://rarediseases.org/rare-diseases/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. Interestingly, COL4A1 and COL4A2 mutations appear to lead to generally similar outcomes although COL4A2 mutations occur less frequently. IV-3 was diagnosed with ventriculomegaly in utero. Urine analysis to test for blood or excess protein can be used to evaluate renal function and identify if the kidneys might be affected. Aguglia U, Gambardella A, Breedveld GJ, Oliveri RL, Le Piane E, Messina D, et al. Further refinement of COL4A1 and COL4A2 related cortical malformations. mutations: a novel genetic multisystem disease. Breedveld G, De Coo IF, Lequin MH, Arts WFM, Heutink P, Gould DB, et al. The networks formed by the COL4A1 and COL4A2 proteins are called basement membranes and are present in every organ of the body. The reference sequences were NM_001845.4 (NP_001836.2) for COL4A1 and NM_001846.2 (NP_001837.2) for COL4A2. Copyright 2023 by Gould Syndrome Foundation -. mutation in Axenfeld-Rieger anomaly with leukoencephalopathy and stroke. Individuals with HANAC syndrome also experience a variety of eye problems. The effects of the disorder range from subtle or mild to severe, depending on associated brain abnormalities. Migraines can occur with or without aura. doi: 2015;17:843-853. https://www.nature.com/articles/gim2014210, Yoneda Y, Haginoya K, Kato M, et al. 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). Received: 06 January 2020; Accepted: 01 July 2020; Published: 11 September 2020. A novel COL4A1 gene mutation results in autosomal dominant non-syndromic congenital cataract in a Chinese family. I dont think we will ever be able to truly articulate our appreciation for Dr. Madsen and Boston Childrens for all that they did for Zeeva and our family. NCI CPTC Antibody Characterization Program. Rannikme K, Davies G, Thomson PA, Bevan S, Devan WJ, Falcone GJ, et al. 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. Zenteno JC, Cresp J, Buentello-Volante B, Buil JA, Bassaganyas F, Vela-Segarra JI, et al. Hereditary angiopathy with nephropathy, aneurysms, and muscle cramps (HANAC) syndrome is part of a group of conditions called the COL4A1-related disorders. This condition causes mutations in genes that produce a specific type of collagen. J Med Genet. 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. 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 doi: 10.1212/WNL.0b013e3181eee440, 28. I cannot describe the feeling of seeing your child healed. 2018;91:e2078-e2088. Ronco P. Cerebrovascular disease related to COL4A1 mutations in HANAC syndrome. doi: 10.1136/jmg.2005.035584, 15. Yet, as for all COL4A1 mutations, no specific treatment is currently available, and, due to the variable penetrance, adapted follow-up is challenging. (2002) 112:198202. Children inherit a full complement of chromosomes from each of their parent and so we carry two copies of each gene. 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. Eur J Paediatr Neurol. Written informed consent was obtained from the patient and the patient's parents for publication of this case report. If individuals have muscle cramps, blood tests can reveal elevated levels creatine kinase, which is a muscle enzyme. NORD strives to open new assistance programs as funding allows. Nat Methods. Other eye problems associated with HANAC syndrome include a clouding of the lens of the eye (cataract) and an abnormality called Axenfeld-Rieger anomaly. Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, et al. Full ophthalmological evaluations including slit lamp and fundoscopy were realized and disclosed for bilateral hypermetropia in IV-3 [15 dioptre (D)], IV-6 (8.5 D), IV-5 (10 D), and III-3 (7 D). Careers. What are the different ways a genetic condition can be inherited? Suite 500 HHS Vulnerability Disclosure, Help The causative gene of HANAC is COL4A1 (13q34) encoding the alpha1 chain of collagen IV, a major component of basement membranes also involved in . 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. (2010). Gould Syndrome is diagnosed following a genetic test revealing a mutation in COL4A1 or COL4A2. In the back of the eye, affected individuals have also twisting or distortion (tortuosity) of arteries in the retina (bilateral retinal arterial tortuosity) as part of the syndrome or as an isolated finding. When this enzyme is elevated, it is a sign of muscle damage. 128:4839. 2018;61:765-772. We connect and coordinate our families with researchers and medical professionals to get our disease and management coordination into the medical realm. doi: 10.1212/WNL.0b013e3181c3fd12, 9. Neurology. All individuals with this condition have arteries that twist and turn abnormally within the light-sensitive tissue at the back of the eyes (arterial retinal tortuosity). This can lead to problems 1) if too much of the misfolded protein accumulates within cells, 2) if not enough of the protein exits the cells to form networks, and 3) occasionally, the presence of the mutant proteins outside the cells can interfere with the structure of the network. Some people with COL4A1-related brain small-vessel disease have an eye abnormality called Axenfeld-Rieger anomaly. At least 50 individuals with this condition have been described in the scientific literature. Available at: https://www.ncbi.nlm.nih.gov/books/NBK7046/ Accessed January 28, 2019. Stroke is a leading cause of death and serious long-term disability in developed nations. This review dsecribes the clinical spectrum of a newly identified disorder related to COL4A1 gene mutations. The management of COL4A1/A2-related disorders may require the coordinated efforts of a team of specialists. Mutations in COL4A3, COL4A4 and COL4A5 were found in the early 1990's in patients with Alport Syndrome. Still other individuals may not develop any symptoms until well into adulthood. 2009 Dec 1;73(22):1873-82. doi: 10.1212/WNL.0b013e3181c3fd12. Molecular analysis was performed on a gDNA level by means of PCR amplification of all the coding exons and the flanking intron region. Stroke is often the first symptom of this condition, typically occurring in mid-adulthood. The age of onset, severity, specific symptoms and disease progression varies greatly from one person to another, even among members of the same family. We recently described hereditary angiopathy with nephropathy, aneurysm, and muscle cramps (HANAC) syndrome in 3 families with closely localized COL4A1 mutations. COL4A1/A2-related disorders can also be associated with a variety of abnormalities affecting the front or back of the eyes. MedlinePlus links to health information from the National Institutes of Health and other federal government agencies. Arch Ophthalmol. The variant was confirmed by bidirectional fluorescence DNA sequencing (Sanger method). To date, over 50 pathogenic or likely pathogenic variants have been described in the COL4A1 gene, most of them missense (2). Matrix Biol. Neuropediatrics. doi: 10.1212/WNL.0000000000000837, 20. Please note that NORD provides this information for the benefit of the rare disease community. Bookshelf Teaching families how to advocate for their loved ones and access medical information. COL4A1/A2-related disorders are caused by dominant mutations in the COL4A1 or COL4A2 genes. N Engl J Med. Lenses corrected for hypermetropia. Together, these studies suggest that certain unknown variants of COL4A1 and COL4A2 might contribute to chronic vascular dysfunction. (D) III- 3Brain MRI showed small asymptomatic lesions in white matter. IV-3 and IV-6 are closely followed by a neuropediatrician (VW). Most individuals diagnosed with a COL4A1-related disorder have an affected parent. Similar blood vessel weakness and breakage occurs in the eyes of some affected individuals. Basement membranes without these networks are unstable, leading to weakening of the tissues that they surround. 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). To use the sharing features on this page, please enable JavaScript. Novel heterozygous COL4A2 variant c.2572A>G, p.(I858V) mimicking Sneddon's and Divry van Bogaert Syndrome. https://www.clinicaltrialsregister.eu/, JOURNAL ARTICLES Children with the most severe brain malformations may have: Intellectual impairment Seizures Hydrocephalus Spasticity People who have a disorder of the corpus callosum typically have: 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. Gould Syndrome is a rare, genetic, multi-system disorder. 2011 (2014) 15:16. mutations: a novel genetic multisystem disease. The cells of the retina trigger nerve impulses that run from the optic nerve to the brain to form sight. Autosomal Dominant Brain Small Vessel Disease. Copyright 2020 Scoppettuolo, Ligot, Wermenbol, Van Bogaert and Naeije. He would separate the two halves of her brain by A diagnosis of COL4A1/A2-related disorders is based upon identification of characteristic symptoms, a detailed patient and family history, a thorough clinical evaluation and a variety of specialized tests including advanced imaging techniques. The latest research shows that insufficient COL4A1/A2 in basement membranes damages different tissues in very different ways. Molecular analysis in the father disclosed a heterozygous variant c.2228G>T (p.Gly743Val) in exon 30 of the COL4A1 gene that segregated with the phenotype. Some individuals with COL4A1-related brain small-vessel disease do not have any signs or symptoms of the condition. What does it mean to have a COL4A1 gene mutation: The COL4A1 gene provides instructions for making one component of type IV collagen, which is a flexible protein important in the structure of many. 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. In the eye, patients may have retinal arteriolar tortuosities and retinal hemorrhages or anterior segment dysgenesis. Bethesda, MD 20894, Web Policies Fragile or damaged blood vessels or basement membranes in the kidneys can lead to blood in the urine (hematuria). It affects mainly young adults, children and more typically neonates. Quincy, MA 02169 Collagen type IV alpha 1 (COL4A1) and 2 (COL4A2) are extracellular matrix proteins that together constitute a major component of nearly all basement membranes. A diagnosis can be confirmed through molecular genetic testing. In a retrospective study of 52 patients with COL4A1 mutations, stroke occurred in 17.3% of subjects and MRI showed white matter abnormalities (63.5%), subcortical microbleeds (52.9%), porencephaly (46%), enlarged spaces around blood vessels, (19.2%), and small infarctions (13.5%). She had seizures every day, couldnt gain weight, sleep right, or generally enjoy her life. (2004) 62:16135. This is not specific to COL4A1/A2-related disorders, and is a sign of many different types of muscle disease. doi: 10.1001/archneur.1983.04050080067013, 17. (1982) 40:5679. Summary. 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. (2010) 14:1827. Over 100 families have been identified with these disorders in the medical literature and many more cases are known that are not in the published literature. (2015) 17:84353. Stroke subtype, vascular risk factors, and total MRI brain small-vessel disease burden. 2010 Oct;152A(10):2550-5. doi: 10.1002/ajmg.a.33659. 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. (2009) 73:187382. ), A variety of rare genetic disorders may have symptoms similar to those found in COL4A1/A2-related disorders. Facebook: https://www.facebook.com/Col4A1Foundation Please Note 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. eCollection 2021. The conditions in this group have a range of signs and symptoms that involve fragile blood vessels. Cerebrovascular disease related to COL4A1 mutations in HANAC syndrome. The X and Y chromosomes are called the sex chromosomes and the rest all are called 'autosomes'. COL4A1 and COL4A2 mutations and disease: insights into pathogenic mechanisms and potential therapeutic targets. functional hemispherectomy. Shah S, Ellard S, Kneen R, Lim M, Osborne N, Rankin J, et al. Unable to load your collection due to an error, Unable to load your delegates due to an error. Probands' father had severe hypermetropia and bilateral cataracts. Antiinflammatory therapy with canakinumab for atherosclerotic disease. In addition to providing strength and support to tissues, basement membranes provide instructional cues to cells. 10.1161/STROKEAHA.110.581918. COL4A1 encodes type IV collagen 1 chain, a crucial component of nearly all basement membrane including vasculature, renal glomerule and ocular structures. 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. Contact a health care provider if you have questions about your health. COL4A2 mutation causing adult onset recurrent intracerebral hemorrhage and leukoencephalopathy. However, in people with HANAC syndrome, these aneurysms typically do not burst. Copyright 2023 NORD National Organization for Rare Disorders, Inc. All rights reserved. Seattle, WA: University of Washington, Seattle; 1993-. Pathology. He underwent at birth neurosonography for axial hypotonia that revealed ventricular asymmetry and right frontotemporal dilatation (Figure 3). Phone: 203-263-9938 Gould Syndrome is often 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. How can gene variants affect health and development? COL4A1 mutations and hereditary angiopathy, nephropathy, aneurysms, and muscle cramps. Ultrasound in utero from IV-6 (A). Abnormal retinal arteries are prone to rupture causing bleeding associated with temporary loss of vision or even retinal detachments that can cause permanent vision loss. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site. In people with HANAC syndrome, angiopathy affects several parts of the body. Eur J Med Genet. 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. Recent findings: NORD is a registered 501(c)(3) charity organization. January 31, 2019 Other causes of porencephaly were ruled out [maternal alloimmunization, trauma, peri-natal cerebral ischemia (normal Apgar scores at birth), and negative TORCH complex tests]. (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). He smiled, caught it, and asked Zeeva if he could throw it back. (2014) 252:178994. Epub 2010 Jun 17. All authors contributed to the article and approved the submitted version. doi: 10.1126/science.1109418, 5. In addition to porencephaly there can be other forms of damage to the brain present at birth. Curr Opin Neurol. The retina was collected and immunolabeled with an anti-collagen IV antibody, for reconstruction of the entire vascular network (Fig. Gould DB, Phalan FC, van Mil SE, Sundberg JP, Vahedi K, Massin P, et al. 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 Suite 500 Neurol. 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. COL4A1 codes for extracellular matrix proteins that form heterotrimers that are major components of nearly all organ basal membranes. Am J Neuroradiol. Vahedi K, Alamowitch S. Clinical spectrum of type IV collagen (COL4A1) Curr Med Chem. Internet. As a result, the skin around the affected area may turn white or blue for a brief period of time and the area may tingle or throb. Orignac I, Dousset V, Lacombe D, Orgogozo JM, Arveiler B, Goizet C. COL4A1 2017;155:45-57. https://www.ncbi.nlm.nih.gov/pubmed/28254515, Alavi MV, Mao M, Pawlikowski BT, et al. 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. When our 8-year-old daughter, Zeeva, giggles and runs in her walker to the swing set, its like watching pure childhood joy. Painful muscle cramps can occur and can develop before three years of age. Interpretation of variant significance was done according to the American College of Medical Genetics and Genomics (ACMG) standards and guidelines (20). Before Type IV collagen is an important component of basement membranes in many tissues, especially blood vessels 1-6. Other patients have been reported with cysts on the liver, irregular heartbeats (supraventricular arrhythmia), and Raynaud phenomenon, which is in which the fingers or toes become numb or have a prickly sensation in response to cold due to narrowing of blood vessels. The expanding phenotype of COL4A1 and COL4A2 mutations: clinical data on 13 newly identified families and a review of the literature. 2021 Sep 10;13:727590. doi: 10.3389/fnagi.2021.727590. ACS Omega. 1A-B). This raises questions about what tests Liliane has a lot to be grateful for this holiday season. The proportion of cases caused by a de novopathogenic variant is estimated to be at least 27%. COL4A1 is an essential component for basal membrane stability. and transmitted securely. Glaucoma is initially treated with topical medications and, if medical therapy is unsuccessful, surgery. For the nucleotide numbering, the HVGS terms (www.hgvs.org) were applied with the nucleotide A of the ATG startcodon = c.1. Various muscles can be affected and muscle strength can become weakened. Aicardi-Goutieres syndrome - About the Disease - Genetic and Rare Diseases Information Center National Center for Advancing Translational Sciences Browse by Disease About GARD Contact Us We recently launched the new GARD website and are still developing specific pages. 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. Changing lives of those with rare disease. Dominant genetic disorders occur when only a single copy of a non-working gene is necessary to cause a particular disease. When these ropes are secreted, they assemble into net-like structures outside the cells. Prenatal clinical manifestations in individuals with COL4A1/2 variants. During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of certain tissue structures. Neurology. No use, distribution or reproduction is permitted which does not comply with these terms. II-2 had a limp since childhood attributed to forceps delivery. The pathogenic mechanisms of COL4A1 mutations are not fully elucidated and may vary according to the mutation type, the affected exon (mutations responsible for systemic HANAC syndrome cluster at exon 24 and 25), the position of the mutation within the triple-helix domain, and the mutation location. This study clearly demonstrates that COL4A1 and COL4A2 mutations cause clinically variable cerebrovascular disease that includes characteristic features of cerebral small vessel disease. IV-5Brain MRI revealing porencephalic cyst of frontal horn of lateral right ventricle (C). 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. 2022 May 27;13:827165. doi: 10.3389/fneur.2022.827165. 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). 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). It is ubiquitously expressed in many tissues and cell types. J Neurol Sci. Plaisier E, Ronco P. COL4A1-Related Disorders. small vessel disease: a systematic review. Washington, DC 20036 Standardized human pedigree nomenclature: update and assessment of the recommendations of the National Society of Genetic Counselors. Fazekas F, Chawluk JB, Alavi A. MR signal abnormalities at 1.5 T in Alzheimer's dementia and normal aging. 1779 Massachusetts Avenue These protein networks are the main component of basement membranes, which are thin sheet-like structures that separate and support cells in many tissues. COL4A1/A2-related disorders are rare, genetic, multi-system disorders. doi: 10.1056/NEJMoa053727, 7. Clin Genet. In the front of the eye, patients can have abnormally small eyes (microphthalmia), cataracts (cloudy lenses), and anterior segment dysgenesis (Axenfeld-Rieger). The COL4A1 gene provides instructions for making one component of a protein called type IV collagen. The p.Gly743Val variant is a conservative substitution that occurs in a position highly conserved across species (SIFT analysis: DeleteriousScore 0, median: 4.22, highly conserved nucleotide and amino acid, up to Tetraodon considering 11 species) and affects a crucial and abundant residue within the triple-helix-forming collagenous domain of the protein, which consist of long stretches of Gly-X-Y repeats. Mosaicism can contribute to both reduced penetrance or variable expressivity but other factors do as well. Available at: https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Cephalic-Disorders-Fact-Sheet Accessed January 28, 2019. Additionally, consultation with a genetic counselor is strongly recommended for affected individuals and their families and psychosocial support for the entire family is essential. III-3 was informed of the genetic diagnosis and is now regularly followed and screened for cataracts and brain aneurysms. Hum Mol Genet. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. The conditions in this group have a range of signs and symptoms that involve fragile blood vessels. 30. 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 (24), hemorrhage (2, 57) and aneurysms (8)], ophthalmological (912) (retinal artery tortuosity, Axenfeld Rieger anomalies, cataracts, and severe hypermetropia), renal (13) (renal cysts, and microscopic hematuria), and systemic (13) findings (cramps with a high creatine kinase level [CK], Raynaud's phenomenon, and arrhythmias). Compared to other COL4A1-related disorders, the brain is only mildly affected in HANAC syndrome. Bone. Neurology. official website and that any information you provide is encrypted sharing sensitive information, make sure youre on a federal Berg R, Aleck A, Kaplan A. Familial porencephaly. However, in rare pathologies with few cases, we may have missed undescribed or subclinical manifestations. In people with HANAC syndrome, the vasculature and other tissues within the kidneys, brain, muscles, eyes, and throughout the body weaken. Arterial retinal tortuosity can cause episodes of bleeding within the eye following any minor trauma to the eye, leading to temporary vision loss. What does it mean if a disorder seems to run in my family? In the human genome, there are 46 chromosomes. She was struggling to advance both cognitively and physically because of uncontrolled epilepsy. An official website of the United States government. 2008 May;192(5):971-84; discussion 984-6. 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/. In most people, small vessel disease in the brain does not cause symptoms. In addition the whole spectrum of the phenotype is not yet known and there are many asymptomatic patients. Phone: 617-249-7300, Danbury, CT office People listened to us and to Zeeva in a very different and proactive way. Individuals with this condition are at increased risk of having more than one stroke in their lifetime. Dr. Madsen suggested Zeeva have an operation called a Therefore, it is important to note that there is a very broad spectrum of clinical presentations with different organs affected to different degrees between patients. 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. Participants with epilepsy frequently reported developmental delays (88.6%), stroke (60.0%), cerebral palsy (65.7%), and constipation (57.1%). The inheritance pattern is autosomal dominant (14) and age-dependent with almost 100% penetrance. Collagen alpha-1(IV) chain (COL4A1) is a protein that in humans is encoded by the COL4A1 gene on chromosome 13. No microbleeds or cystic cavities were found. 8600 Rockville Pike INTERNET Changing lives of those with rare disease. Cerebrovascular disease related to COL4A1 mutations in HANAC syndrome. At least six affected families have been described in the scientific literature. NORD is not a medical provider or health care facility and thus can neither diagnose any disease or disorder nor endorse or recommend any specific medical treatments.