Cysts can also form in one or both kidneys, and the cysts may grow larger over time. 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 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. 2010 Aug;41(8):e513-8. At 1 month of age, a neuropediatric examination disclosed normal neck muscle tonus, normal Moro reflex, bilateral placing reaction, and open hands. doi: 10.1212/WNL.0b013e3181c3fd12, 9. Yet, as for all COL4A1 mutations, no specific treatment is currently available, and, due to the variable penetrance, adapted follow-up is challenging. The human phenotypes are extremely variable between patients and between families, with disease onset as early as in the fetal period. Affected infants and children can exhibit delays in reaching developmental milestones and varying degrees of intellectual disability. These genes are the blueprints for two proteins that wind together like a long rope inside cells.
COL4A1 brain small-vessel disease - Radiopaedia COL4A1-related brain small-vessel disease - MedlinePlus Neurol. 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. Zenteno JC, Cresp J, Buentello-Volante B, Buil JA, Bassaganyas F, Vela-Segarra JI, et al. Washington, DC 20036 Suite 500 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). Meuwissen MEC, Halley DJJ, Smit LS, Lequin MH, Cobben JM, De Coo R, et al. Some of these patients have been described as having HANAC syndrome, which is an acronym for hereditary angiopathy, nephropathy, aneurysms, and muscle cramps. Changing lives of those with rare disease. A dominantly inherited mutation in collagen IV A1 (COL4A1) causing childhood onset stroke without porencephaly.
Col4a1 mutation generates vascular abnormalities correlated with The disorder causes many symptoms, not the least of which are strokes and epilepsy. eCollection 2022 Nov 8. Our experience with Boston Childrens was very different from the other places we had been for epilepsy and neurology treatment. When our 8-year-old daughter, Zeeva, giggles and runs in her walker to the swing set, its like watching pure childhood joy. (2006) 43:4905. (2006) 354:148996. The COL4A2 test was negative. Shah S, Kumar Y, McLean B, Churchill A, Stoodley N, Rankin J, et al. Axenfeld-Rieger anomaly and cataract can cause impaired vision. Some individuals develop cysts on the kidney.
Gould Syndrome - COL4A1 - COL4A2 genes - Gould Syndrome Foundation The ultimate goal of IAMRARE is to unite patients and research communities in the improvement of care and drug development. To better define pathology caused by Col4a1 mutations, we characterized myopathy in two different Col4a1 mutant mouse strainsCol4a1 ex41 and Col4a1 G394V.We selected these strains from an allelic series of Col4a1 mutant mice because they showed the most severe myopathy according to NPN quantification in quadriceps while having different effects on [1(IV)] 2 2(IV) secretion. COL4A1 mutations as a monogenic cause of cerebral small vessel disease: a systematic review. Yoneda Y, Haginoya K, Kato M, Osaka H, Yokochi K, Arai H, et al. Additionally, consultation with a genetic counselor is strongly recommended for affected individuals and their families and psychosocial support for the entire family is essential. By continuing to use this website, you agree to the Terms of Service & Privacy Policy. Many patients with COL4A1 and COL4A2 mutations have additional signs and symptoms that do not include the cerebral vasculature. Gould Syndrome is an ultra rare genetic, multi-system disorder. Sibon I, Coupry I, Menegon P, Bouchet JP, Gorry P, Burgelin I, Calvas P, MedlinePlus also links to health information from non-government Web sites. 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. She also showed severe hypermetropia. 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. Please note that NORD provides this information for the benefit of the rare disease community. Lanfranconi S, Markus HS. 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. 128:4839. There is in addition a specific phenotype called HANAC with constant nephropathy, muscle cramps and frequent intracranial aneurysms. doi: 10.1212/WNL.0000000000001309, 8. Genet Med. (2010) 14:1827. 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. So far, it appears as though mutations in COL4A1 and COL4A2 lead to identical disease, however, for reasons that are not yet understood, mutations in COL4A2 are much less frequent than those in COL4A1. This condition causes mutations in genes that produce a specific type of collagen. 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. IV-3 goes to a normal school, but special schooling is required for IV-6. (2011) 42:13. Focke JK, Veltkamp R, Bauer P, Kraemer M. J Neurol. But she is learning to read, enjoys swimming, horseback riding, and is a glass jewelry and pottery artist. (2005) 308:116771. Vermeulen RJ, Peeters-Scholte C, Van Vugt JJMG, Barkhof F, Rizzu P, Van der Schoor SRD, et al. IV-5Brain MRI revealing porencephalic cyst of frontal horn of lateral right ventricle (C). Systemic work-up including renal function, CK levels, urinary sediment test, and renal ultrasound proved unremarkable. Porencephaly refers to the formation of fluid-filled cysts or cavities within of the brain. Alamowitch S, Plaisier E, Favrole P, Prost C, Chen Z, Van Agtmael T, Marro B, Seattle, WA: University of Washington, Seattle; 1993-. Copyright 2023 by Gould Syndrome Foundation -, https://rarediseases.org/rare-diseases/col4a1-a2-related-disorders/. Cataracts, which are a clouding of the lenses of the eyes, are often present from birth (congenital) and may be one of the first identifiable signs of the syndrome.
Epilepsy and related challenges in children with COL4A1 and - PubMed Acute urinary retention due to a novel collagen COL4A1 mutation. In addition to porencephaly there can be other forms of damage to the brain present at birth. 2012;54:569-574. https://www.ncbi.nlm.nih.gov/pubmed/22574627, Lanfranconi S, Markus HS. 2015;84:918-926. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4351667/, Meuwissen ME, Halley DJ, Smit LS, et al.
What is Gould Syndrome? - Gould Syndrome Foundation Various treatments have been reported in the medical literature as part of single case reports or small series of patients. Another limitation is the systemic work-up based on described phenotypes and supposed affected organs. The conditions in this group have a range of signs and symptoms that involve fragile blood vessels.
Novel COL4A1 mutation in a fetus with early prenatal onset of - Nature Comparison of Clinical, Radiographic, and Histological Features in COL4A1 Syndrome Compared With Other Single Gene Disorders Causing SVD. 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. At least six affected families have been described in the scientific literature. Plaisier E, Ronco P. COL4A1-Related Disorders.
Orphanet: HANAC syndrome 2007 Aug;62(2):177-84. doi: 10.1002/ana.21191. Copyright 2023 NORD National Organization for Rare Disorders, Inc. All rights reserved. People with HANAC syndrome develop kidney disease (nephropathy). 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. If we dont have a program for you now, please continue to check back with us. https://www.ncbi.nlm.nih.gov/pubmed/26610912. An MRI uses a magnetic field and radio waves to produce cross-sectional images of particular organs and bodily tissues, including the brain. Further refinement of COL4A1 and COL4A2 related cortical malformations. 1900 Crown Colony Drive COL4A1/A2-related disorders are rare, genetic, multi-system disorders. Gould Syndrome is an ultra rare genetic, multi-system disorder. One year later, right hemiparesis became clinically evident with a lack of right voluntary hand prehension in association with right hemineglect. Individuals with COL4A1/A2-related disorders have characteristic patterns of brain disease when viewed under advanced imaging techniques. ClinVar; [VCV000389182.3]. All patients suffering from HANAC syndrome display retinal arteriolar tortuosity and occasional retinal hemorrhages. When these ropes are secreted, they assemble into net-like structures outside the cells. III-3 was informed of the genetic diagnosis and is now regularly followed and screened for cataracts and brain aneurysms. Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, et al. These protein networks are the main component of basement membranes, which are thin sheet-like structures that separate and support cells in many tissues. This variant highlights that the COL4A1 mutation should be sought in cases of familial ophthalmologic pathologies associated with congenital porencephaly or early onset leukoencephalopathy. doi: 10.1016/j.ejpn.2009.04.010, 27. Mutations in COL4A1 or COL4A2 cause Gould Syndrome and, because these two proteins are found in almost all tissues; nearly any organ can be affected. These proteins have very restricted expression and Alport Syndrome primarily affects the kidneys with variable involvement of the eye and cochlea (hearing). BMC Med Genet. Probands' father had severe hypermetropia and bilateral cataracts. Arch Ophthalmol. Internet. Neurology.
Cerebrovascular disease related to COL4A1 mutations in HANAC syndrome https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282239/. Type IV collagen is an important component of basement membranes in many tissues, especially blood vessels 1-6. In most cases, an affected person has one parent with the condition. Orignac I, Dousset V, Lacombe D, Orgogozo JM, Arveiler B, Goizet C. COL4A1 Breedveld G, De Coo IF, Lequin MH, Arts WFM, Heutink P, Gould DB, 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. A similar term, variable expressivity, describes when affected individuals have widely varying signs and symptoms. Xia XY, Li N, Cao X, Wu QY, Li TF, Zhang C, et al. Abnormal blood vessels in the brain are a major consequence of COL4A1 and COL4A2 gene mutations. Gould DB, Phalan FC, van Mil SE, Sundberg JP, Vahedi K, Massin P, et al. Hum Mol Genet. The site is secure.
Agenesis of the Corpus Callosum | National Institute of Neurological Facebook: https://www.facebook.com/Col4A1Foundation Please Note This report highlights both the broad spectrum of COL4A1 mutations and the yield of testing the COL4A1 gene in familial ophthalmological and brain disorders. (2010). https://nord1dev.wpengine.com/for-patients-and-families/information-resources/info-clinical-trials-and-research-studies/, For information about clinical trials sponsored by private sources, contact: