col4a1 syndrome life expectancy col4a1 syndrome life expectancy

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. Contact a health care provider if you have questions about your health. 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. III-3 was asymptomatic but for severe hypermetropia and bilateral cataracts. COL4A1 mutations and hereditary angiopathy, nephropathy, aneurysms, and muscle cramps. The team may eventually include pediatric neurologists (diagnose and treat disorders of the brain, nerves and nervous system in children); ophthalmologists (who specialize in eye disorders) hematologists (who specialize in blood disorders); cardiologists (who specialize in heart disorders, nephrologists (who specialize in kidney disorders) and other healthcare professionals may need to systematically and comprehensively plan treatment. How can gene variants affect health and development? Ann Neurol. 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. Subsequently, it has been recognized that autosomal dominant COL4A1 and COL4A2 mutations cause a broad spectrum of cerebrovascular disease, whose onset occurs from fetal life onward and whose severity may range from small-vessel disease to fatal intraparenchymal hemorrhage.,, While epilepsy is known to be a clinical feature of porencephaly, the Cereb Circ Cogn Behav. Type IV Collagens and Basement Membrane Diseases: Cell Biology and Pathogenic Mechanisms. Standardized (15) familiar pedigree is showed in Figure 1. J Med Genet. Your support helps to ensure everyones free access to NORDs rare disease reports. As a result, type IV collagen molecules cannot attach to each other to form the protein networks in basement membranes. Neurology. Congenital Cephalic Disorders His bedside manner was incredible. The cells of the retina trigger nerve impulses that run from the optic nerve to the brain to form sight. COL4A1 mutations as a monogenic cause of cerebral We each inherit a full complement on autosomes from each of our parents giving us two copies of each gene. 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. Cysts can also form in one or both kidneys, and the cysts may grow larger over time. 128:4839. Comparisons may be useful for a differential diagnosis: CADASIL is a rare genetic disorder affecting the small blood vessels in the brain. This is not specific to COL4A1/A2-related disorders, and is a sign of many different types of muscle disease. 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). Am J Neuroradiol. Early intervention is important in ensuring that children with reach their highest potential. Urine analysis to test for blood or excess protein can be used to evaluate renal function and identify if the kidneys might be affected. Other eye problems experienced by people with COL4A1-related brain small-vessel disease include clouding of the lens of the eye (cataract) and the presence of arteries that twist and turn abnormally within the light-sensitive tissue at the back of the eye (arterial retinal tortuosity). COL4A1/A2-related disorders are rare, genetic, multi-system disorders. 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). Phone: 202-588-5700. Firstly, it segregates within the family with the phenotype. 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). It affects mainly young adults, children and more typically neonates. Mosaicism can contribute to both reduced penetrance or variable expressivity but other factors do as well. 8600 Rockville Pike An MRI uses a magnetic field and radio waves to produce cross-sectional images of particular organs and bodily tissues, including the brain. Common variation in COL4A1/COL4A2 is associated with sporadic cerebral small vessel disease. 1779 Massachusetts Avenue Autosomal Dominant Familial Porencephaly Type I. We describe here the phenotype of a likely pathogenic gene variant, p.Gly743Val, which is responsible for a missense mutation in the COL4A1 gene exon 30 in a three generation family with severe hypermetropia and highly penetrant porencephaly in the absence of systemic manifestations. Facebook: https://www.facebook.com/Col4A1Foundation Please Note In: Pagon RA, Bird TD, Dolan CR, et al., GeneReviews. Cerebrovascular disease related to COL4A1 mutations in HANAC syndrome. (1982) 40:5679. 2021 Sep 10;13:727590. doi: 10.3389/fnagi.2021.727590. Painful muscle cramps can occur and can develop before three years of age. Stay Informed With NORDs Email Newsletter, Launching Registries & Natural History Studies. Phenotypic spectrum of COL4A1 mutations: porencephaly to schizencephaly. Zagaglia S, Selch C, Nisevic JR, Mei D, Michalak Z, Hernandez-Hernandez L, et al. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). (2008) 17:42433. The surgery doi: 10.1212/WNL.0b013e3181eee440, 28. functional hemispherectomy. In addition the whole spectrum of the phenotype is not yet known and there are many asymptomatic patients. for the triple helical CB3[IV] domain. Oct;152A(10):2550-5. doi: 10.1002/ajmg.a.33659. Axenfeld-Rieger anomaly and cataract can cause impaired vision. Arterial retinal tortuosity can cause episodes of bleeding within the eye following any minor trauma to the eye, leading to temporary vision loss. Novel mutations in three families confirm a major role of COL4A1 in hereditary porencephaly. In the human genome, there are 46 chromosomes. 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. 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. Arch Neurol. Zenteno JC, Cresp J, Buentello-Volante B, Buil JA, Bassaganyas F, Vela-Segarra JI, et al. Aguglia U, Gambardella A, Breedveld GJ, Oliveri RL, Le Piane E, Messina D, et al. Changing lives of those with rare disease. Bone. What are the different ways a genetic condition can be inherited? (2017) 377:111931. The severity of the condition varies greatly among affected individuals. Arch Ophthalmol. 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. In people with COL4A1-related brain small-vessel disease, the vasculature in the brain weakens, which can lead to blood vessel breakage and stroke. Molecular Dynamics Investigation on the Effects of Protonation and Lysyl Hydroxylation on Sulfilimine Cross-links in Collagen IV. As a result, type IV collagen molecules cannot attach to each other to form the protein networks in basement membranes. These types of correlations can be difficult to detect in patients because of the broad genetic variability in humans. 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. Novel COL4A1 mutations associated with HANAC syndrome: a role for the triple helical CB3[IV] domain. 2017 Jan;66:100-103. doi: 10.1016/j.pediatrneurol.2016.04.010. Gould Syndrome is a rare, genetic, multi-system disorder. Disclaimer. (2015) 84:91826. Therapies are based on the specific symptoms in each individual. This group rarely survives beyond 2 years. MedlinePlus also links to health information from non-government Web sites. 2012;322:25-30. https://www.ncbi.nlm.nih.gov/pubmed/22868088, Shah S, Ellard S, Kneen R, et al. Comparison of Clinical, Radiographic, and Histological Features in COL4A1 Syndrome Compared With Other Single Gene Disorders Causing SVD. The conditions in this group have a range of signs and symptoms that involve fragile blood vessels. Affected individuals may also experience seizures and migraine headaches accompanied by visual sensations known as auras. As the name suggests, mutations in the COL4A1 gene cause COL4A1-related brain small vessel disease. We provide education, advocacy, and resources for families and individuals affected. 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). Eur J Paediatr Neurol. 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. This report highlights both the broad spectrum of COL4A1 mutations and the yield of testing the COL4A1 gene in familial ophthalmological and brain disorders. cutting tissue called the corpus callosum, then make some additional delicate 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/. NORD strives to open new assistance programs as funding allows. Ann Illumina's Sequencing by Synthesis (SBS) technology (MiSeq Personal Sequencer, Illumina) analyzed the generated amplicons. Some individuals do not have any observable symptoms (asymptomatic); others can develop severe, even life-threatening complications. Research in mice with Col4a1 mutations suggests that the position of the mutation is very important. MedlinePlus links to health information from the National Institutes of Health and other federal government agencies. 2014 Mar;261(3):500-3. doi: 10.1007/s00415-013-7224-4. Individuals with HANAC syndrome also experience a variety of eye problems. Bookshelf 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. COL4A1/A2-related disorders are caused by dominant mutations in the COL4A1 or COL4A2 genes. Clin Neurol Neurosurg. Please note that NORD provides this information for the benefit of the rare disease community. Dominant genetic disorders occur when only a single copy of a non-working gene is necessary to cause a particular disease. People with HANAC syndrome develop kidney disease (nephropathy). Probands' father had severe hypermetropia and bilateral cataracts. Common variation in COL4A1/COL4A2 is associated with sporadic cerebral small vessel disease. Shah S, Ellard S, Kneen R, Lim M, Osborne N, Rankin J, et al. 55 Kenosia Avenue The disorder causes many symptoms, not the least of which are strokes and epilepsy. The blood vessels as well as thin sheet-like structures called basement membranes that separate and support cells are weakened and more susceptible to breakage. Image showed ventricular asymmetry and brain MRI confirmed right frontotemporal dilatation (B). COL4A1/COL4A2 gene mutations description, symptoms and the sub-diagnosis. This analysis represents a subanalysis of the 35 out of 60 children <=18 years of age who reported a history of seizures. (2014) 34:757. 2010;17(13):1317-24. doi: (D) III- 3Brain MRI showed small asymptomatic lesions in white matter. Suggestive evidence for linkage to chromosome 13qter for autosomal dominant type 1 porencephaly. In some people, serious, life-threatening complications may occur in infancy; in others, only minor complications may occur and intelligence is unaffected. 2009;73:1873-1882. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2881859/, Mao, M, Alavi MV, Labelle-Dumais, C, Gould DB. Plaisier E, Gribouval O, Alamowitch S, Mougenot B, Prost C, Verpont MC, et al. COL4A1 is an essential component for basal membrane stability. Only one copy of COL4A1 or COL4A2 needs to acquire a mutation in order to cause disease which means the mutations are Dominant thus, Gould Syndrome is considered Autosomal Dominant. The variant was found in IV-3 and IV-5 and not in asymptomatic relatives (III-4, IV-1, IV-4). 2018;91:e2078-e2088. eCollection 2022. Supporting children in their development to reduce handicaps and combining their follow-up with parent counseling could be considered as an ideal approach. Next generation sequencing uncovers a missense mutation in COL4A1 as the cause of familial retinal arteriolar tortuosity. 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). After the COL4A1 mutation was found, systemic manifestations of COL4A1 mutations were investigated. Neurology. Last updated: Fax: 203-263-9938, Washington, DC Office Jeanne M, Gould DB. doi: 10.1212/WNL.0b013e3181c3fd12, 9. In most cases, an affected person has one parent with the condition. In people with HANAC syndrome, the vasculature and other tissues within the kidneys, brain, muscles, eyes, and throughout the body weaken. Suite 310 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. 1900 Crown Colony Drive The ultimate goal of IAMRARE is to unite patients and research communities in the improvement of care and drug development. mutation in Axenfeld-Rieger anomaly with leukoencephalopathy and stroke. 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). Summary: government site. Depending on the cell type that acquires the mutation and when the mutation arises, the individual may have many or few cells with the mutation. Bennett RL, French KS, Resta RG, Doyle DL. It is not uncommon for an unaffected parent to have a severely affected child. The heterozygous variant c.2228G>T [NM_001845.4(COL4A1):c.2228G>T (p.Gly743Val)] was identified in exon 30 of the COL4A1 gene.