col4a1 syndrome life expectancy
COL4A2 mutation causing adult onset recurrent intracerebral hemorrhage and leukoencephalopathy. She had seizures every day, couldnt gain weight, sleep right, or generally enjoy her life. The COL4A1 gene provides instructions for making one component of a protein called type IV collagen. His bedside manner was incredible. doi: In: Pagon RA, Bird TD, Dolan CR, et al., GeneReviews. Your support helps to ensure everyones free access to NORDs rare disease reports. COL4A1/COL4A2 gene mutations description, symptoms and the sub-diagnosis. The conditions in this group have a range of signs and symptoms that involve fragile blood vessels. Vermeulen RJ, Peeters-Scholte C, Van Vugt JJMG, Barkhof F, Rizzu P, Van der Schoor SRD, et al. 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. my mom suggested we call Boston Childrens Hospital. COL4A1 Mutation in a Neonate With Intrauterine Stroke and Anterior Segment Dysgenesis. doi: 10.1055/s-0031-1275343, 24. 10.2174/092986710790936293. 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. In the eye, patients may have retinal arteriolar tortuosities and retinal hemorrhages or anterior segment dysgenesis. Phone: 202-588-5700. doi: 10.1007/s10897-008-9169-9, 16. Abnormal blood vessels in the brain are a major consequence of COL4A1 and COL4A2 gene mutations. The variant was found in IV-3 and IV-5 and not in asymptomatic relatives (III-4, IV-1, IV-4). 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. Gould Syndrome Foundation (COL4a1/COL4A2) seeks to educate the community on the rare disease COL4A1 and it's subcategorical diagnosis'. Exon mutations of the COL4A1 genes are responsible for a broad spectrum of cerebral, ocular, and systemic manifestations. People listened to us and to Zeeva in a very different and proactive way. doi: 10.1016/j.ejpn.2009.04.010, 27. COL4A1 brain small-vessel disease - Radiopaedia Aneurysms are bulges or enlargements of a blood vessel caused by weakening of the wall of the blood vessel. Dev Med Child Neurol. We recently described hereditary angiopathy with nephropathy, aneurysm, and muscle cramps (HANAC) syndrome in 3 families with closely localized COL4A1 mutations. The age of onset, severity, specific symptoms and disease progression varies greatly from one person to another, even among members of the same family. doi: 10.1212/01.WNL.0000123113.46672.68, 25. doi: 10.1056/NEJMoa071906, 14. Neurology. 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 2015;17:843-853. https://www.nature.com/articles/gim2014210, Yoneda Y, Haginoya K, Kato M, et al. doi: 10.1212/WNL.0000000000000837, 20. The causative gene of HANAC is COL4A1 (13q34) encoding the alpha1 chain of collagen IV, a major component of basement membranes also involved in . 2010;17(13):1317-24. doi: NCI CPTC Antibody Characterization Program. Bookshelf (1982) 40:5679. The retina was collected and immunolabeled with an anti-collagen IV antibody, for reconstruction of the entire vascular network (Fig. When our 8-year-old daughter, Zeeva, giggles and runs in her walker to the swing set, its like watching pure childhood joy. Cerebrovascular disease related to COL4A1 mutations in HANAC syndrome. 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. 2012;21:R97-R110. Other causes of porencephaly were ruled out [maternal alloimmunization, trauma, peri-natal cerebral ischemia (normal Apgar scores at birth), and negative TORCH complex tests]. As a result, type IV collagen molecules cannot attach to each other to form the protein networks in basement membranes. Genotype-phenotype correlations in pathology caused by collagen type IV alpha 1 and 2 mutations. J Neurol Sci. N Engl J Med. (2005) 308:116771. Deml B, Reis LM, Maheshwari M, Griffis C, Bick D, Semina E. Whole exome analysis identifies dominant COL4A1 mutations in patients with complex ocular phenotypes involving microphthalmia. It is possible that insufficient collagen in the basement membrane predisposes blood vessels in the brain to leak or rupture. Focke JK, Veltkamp R, Bauer P, Kraemer M. J Neurol. COL4A1/A2-related disorders are caused by dominant mutations in the COL4A1 or COL4A2 genes. Image showed ventricular asymmetry and brain MRI confirmed right frontotemporal dilatation (B). TTY: (866) 411-1010 Probands' father had severe hypermetropia and bilateral cataracts. Schwarz JM, Cooper DN, Schuelke M, Seelow D. Mutationtaster2: Mutation prediction for the deep-sequencing age. Common variation in COL4A1/COL4A2 is associated with sporadic cerebral small vessel disease. BMC Med Genet. The management of COL4A1/A2-related disorders may require the coordinated efforts of a team of specialists. Figure 3. Phone: 203-263-9938 However, in rare pathologies with few cases, we may have missed undescribed or subclinical manifestations. These aneurysms have the potential to burst, causing bleeding within the brain (hemorrhagic stroke). Fax: 203-263-9938, Washington, DC Office doi: 10.1038/nmeth.2890, 22. functional hemispherectomy. Illumina's Sequencing by Synthesis (SBS) technology (MiSeq Personal Sequencer, Illumina) analyzed the generated amplicons. 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. Colin E, Sentilhes L, Sarfati A, Mine M, Guichet A, Ploton C, et al. (2018) 91:e207888. Seattle, WA: University of Washington, Seattle; 1993-. Epub 2022 Apr 14. By continuing to use this website, you agree to the Terms of Service & Privacy Policy. The conditions in this group have a range of signs and symptoms that involve fragile blood vessels. She also showed severe hypermetropia. Some of the patient advocacy organizations listed in the Resources section below provide support and information to affected individuals and their families. Muscle cramps experienced by most people with HANAC syndrome typically begin in early childhood. People with HANAC syndrome develop kidney disease (nephropathy). Xia XY, Li N, Cao X, Wu QY, Li TF, Zhang C, et al. 1900 Crown Colony Drive 1779 Massachusetts Avenue At least six affected families have been described in the scientific literature. A novel COL4A1 gene mutation results in autosomal dominant non-syndromic congenital cataract in a Chinese family. 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. When these ropes are secreted, they assemble into net-like structures outside the cells. Progressive cerebral atrophies in three children with COL4A1 mutations. We therefore began our analysis of mutant Col4a1 G498V mice by examining the retinal vascular network at three and nine months of age. Matrix Biol. Danbury, CT 06810 It is not uncommon for an unaffected parent to have a severely affected child. Epilepsy and related challenges in children with COL4A1 and - PubMed Treatment Internet. We describe, here, the phenotype of a likely pathologic variant (p.Gly743Val) in exon 30 of the COL4A1 gene, responsible for an oculo-cerebral phenotype characterized by severe hypermetropia and highly penetrant porencephaly in absence of other systemic complications. As the name suggests, mutations in the COL4A1 gene cause COL4A1-related brain small vessel disease. 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). Hereditary cerebral small vessel diseases: a review. National Taiwan University Hospital, Taiwan, Kaohsiung Chang Gung Memorial Hospital, Taiwan, Carrera de Medicina, Universidad Cientfica del Sur, Peru, Federal University of Rio Grande do Sul, Brazil. doi: 10.1038/jp.2013.135, 29. Novel COL4A1 mutations associated with HANAC syndrome: a role for the triple helical CB3[IV] domain. (2010). 2011 Plaisier E, Chen Z, Gekeler F, Benhassine S, Dahan K, Marro B, Alamowitch S, Paques M, Ronco P. Am J Med Genet A. This site needs JavaScript to work properly. Molecular analysis was performed on a gDNA level by means of PCR amplification of all the coding exons and the flanking intron region. Agenesis of the Corpus Callosum | National Institute of Neurological COL4A1/A2-related disorders are dominant genetic disorders. Clin Neurol Neurosurg. Clipboard, Search History, and several other advanced features are temporarily unavailable. Background: COL4A1 mutations cause familial porencephaly, infantile hemiplegia, cerebral small vessel disease (CSVD), and hemorrhagic stroke. Orignac I, Dousset V, Lacombe D, Orgogozo JM, Arveiler B, Goizet C. COL4A1 The COL4A1 and COL4A2 genes were screened in proband IV-6. 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). Last updated: Fragile or damaged blood vessels or basement membranes in the kidneys can lead to blood in the urine (hematuria). IV-3 was diagnosed with ventriculomegaly in utero. Individuals with high blood pressure (hypertension) must receive appropriate therapy because of the increased risk of stroke. Basement membranes without these networks are unstable, leading to weakening of the tissues that they surround. The disorder causes many symptoms, not the least of which are strokes and epilepsy. Rare disorders often go misdiagnosed or undiagnosed, making it difficult to determine their true frequency in the general population. Novel COL4A1 mutation in a fetus with early prenatal onset of - Nature doi: 10.1111/j.1469-8749.2011.04198.x, 26. (2004) 62:16135. doi: 10.1212/WNL.0b013e3181c3fd12, 9. 1779 Massachusetts Avenue Here, we report a patient with schizencephaly, detected by fetal ultrasonography and fetal magnetic resonance imaging, with a de novo novel mutation in COL4A1 (c.2645_2646delinsAA, p.Gly882Glu). Neurologic phenotypes associated with COL4A1/2 mutations: expanding the spectrum of disease. The variant was confirmed by bidirectional fluorescence DNA sequencing (Sanger method). sharing sensitive information, make sure youre on a federal Some individuals develop cysts on the kidney. 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). How are genetic conditions treated or managed? 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. Born at term after a 39-week pregnancy, IV-3 had an unremarkable first clinical evaluation at 3 months. The COL4A1 gene has 52 exons and most of the pathogenic variants are distributed across exons 10 to 47 in the triple-helix domain. 2013;73:48-57. https://www.ncbi.nlm.nih.gov/pubmed/23225343, Kuo DS, Labelle-Dumais C, Gould DB. September 2003. COL4A1 encodes type IV collagen 1 chain, a crucial component of nearly all basement membrane including vasculature, renal glomerule and ocular structures. (2014) 15:16. NORD and MedicAlert Foundation have teamed up on a new program to provide protection to rare disease patients in emergency situations. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.). With genetic disorders, the type of mutation, or its location in the gene can sometimes be associated with varying outcomes. PMC For asymptomatic patients, cerebral and vessel imaging for aneurysm screening and ophthalmologic follow-up are indicated (2). Because the collagen is found throughout the body, COL4A1/A2 affects many organ systems, including the brain, kidneys, eyes, and muscles. Comparisons may be useful for a differential diagnosis: CADASIL is a rare genetic disorder affecting the small blood vessels in the brain. Powered by NORD, the IAMRARE Registry Platform is driving transformative change in the study of rare disease. Bennett RL, French KS, Resta RG, Doyle DL. People with this condition may have a bulge in one or multiple blood vessels in the brain (intracranial aneurysms). Stroke is often the first symptom of this condition, typically occurring in mid-adulthood. Symptoms of the following disorders can be similar to those of COL4A1/A2-related disorders. This study clearly demonstrates that COL4A1 and COL4A2 mutations cause clinically variable cerebrovascular disease that includes characteristic features of cerebral small vessel disease. In people with HANAC syndrome, the vasculature and other tissues within the kidneys, brain, muscles, eyes, and throughout the body weaken. In addition to providing strength and support to tissues, basement membranes provide instructional cues to cells. 2018;91:e2078-e2088. These genes are the blueprints for two proteins that wind together like a long rope inside cells. doi: 10.1186/s12881-014-0097-2, 11. This report highlights both the broad spectrum of COL4A1 mutations and the yield of testing the COL4A1 gene in familial ophthalmological and brain disorders. What does it mean if a disorder seems to run in my family? Common variation in COL4A1/COL4A2 is associated with sporadic cerebral small vessel disease. small vessel disease: a systematic review. It looks like nothing was found at this location. (2006) 43:4905. HANAC syndrome is caused by genetic changes in the COL4A1 gene. Because the collagen is found throughout the body, COL4A1/A2 affects many organ systems, including the brain, kidneys, eyes, and muscles. Available at: https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Cephalic-Disorders-Fact-Sheet Accessed January 28, 2019. Purpose of review: 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. IV-6 was born at 35 weeks after a pregnancy marked by gestational diabetes. Novel heterozygous COL4A2 variant c.2572A>G, p.(I858V) mimicking Sneddon's and Divry van Bogaert Syndrome.
