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. COL4A1 is a subunit of the type IV collagen and plays a role in angiogenesis. Schwarz JM, Cooper DN, Schuelke M, Seelow D. Mutationtaster2: Mutation prediction for the deep-sequencing age. https://www.ncbi.nlm.nih.gov/pubmed/20558831, Alamowitch S, Plaisier E, Favrole P, et al. The cells of the retina trigger nerve impulses that run from the optic nerve to the brain to form sight. Please note that NORD provides this information for the benefit of the rare disease community. Axenfeld-Rieger anomaly and cataract can cause impaired vision. Changing lives of those with rare disease. With genetic disorders, the type of mutation, or its location in the gene can sometimes be associated with varying outcomes. She had seizures every day, couldnt gain weight, sleep right, or generally enjoy her life. The .gov means its official. 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. sharing sensitive information, make sure youre on a federal Nearly half of these participants were diagnosed with infantile spasms. Liu X, Yang Q, Tang L, He J, Tian D, Wang B, Xie L, Li C, Fan D. Front Neurol. This study clearly demonstrates that COL4A1 and COL4A2 mutations cause clinically variable cerebrovascular disease that includes characteristic features of cerebral small vessel disease. If we dont have a program for you now, please continue to check back with us. 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). doi: 10.2214/ajr.149.2.351, 19. We are a registered 501(c)3 Nonprofit dedicated to providing hope and help to children and adults with Gould Syndrome; affecting COL4A1 and COL4A2 genes. She was struggling to advance both cognitively and physically because of uncontrolled epilepsy. Ophthalmological features associated with COL4A1 mutations. Lanfranconi S, Markus HS. Suite 310 Berg's criteria was used for porencephaly (16, 17) and white matter hyperintensities were characterized as in Fazekas et al. (No doctor had ever taken a call on their lunch break to speak with me). How are genetic conditions treated or managed? Until just this year, her 16-year-old daughter Emily, who #1 Ranked Childrens Hospital by U. S. News & World Report. COL4A1 disorder is probably largely underestimated because of its multisystem and variable phenotype. Yet, five siblings, showing mild phenotype even in the second generation support a Mendelian transmission with variable expressivity and no other mechanism. Since fewer than 100 families have been reported, the exact prevalence of COL4A1-related disorders is not well-established. Some of these patients have been described as having HANAC syndrome, which is an acronym for hereditary angiopathy, nephropathy, aneurysms, and muscle cramps. Copyright 2020 Scoppettuolo, Ligot, Wermenbol, Van Bogaert and Naeije. doi: 10.1038/gim.2014.210, 3. See our, COL4A1-related brain small-vessel disease, URL of this page: https://medlineplus.gov/genetics/condition/col4a1-related-brain-small-vessel-disease/. Gould Syndrome Foundation (COL4a1/COL4A2) seeks to educate the community on the rare disease COL4A1 and it's subcategorical diagnosis'. (2010) 14:1827. Brain magnetic resonance imaging (MRI) scans were carried out on a three Tesla Brain MRI (Achieva, Ingenia; Philips Healthcare, Best, The Netherlands). 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). As a result, type IV collagen molecules cannot attach to each other to form the protein networks in basement membranes. Zeeva woke up after a ten-hour procedure, opened her eyes, and it felt like we were seeing her for the first time. This review dsecribes the clinical spectrum of a newly identified disorder related to COL4A1 gene mutations. The variant was found in IV-3 and IV-5 and not in asymptomatic relatives (III-4, IV-1, IV-4). Stroke is often the first symptom of this condition, typically occurring in mid-adulthood. 1779 Massachusetts Avenue He also wanted to remove a shunt that was implanted in Zagaglia S, Selch C, Nisevic JR, Mei D, Michalak Z, Hernandez-Hernandez L, et al. Aura refers to additional neurological symptoms that occur with, or sometimes before, the development of the migraine headache. (1982) 40:5679. Born at term after a 39-week pregnancy, IV-3 had an unremarkable first clinical evaluation at 3 months. and transmitted securely. What does it mean if a disorder seems to run in my family? 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. 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 number of genes implicated in epilepsy has grown rapidly in the past decade. Epub 2022 Apr 14. 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. The networks formed by the COL4A1 and COL4A2 proteins are called basement membranes and are present in every organ of the body. Vilain C, Van Regemorter N, Verloes A, David P, Van Bogaert P. Neuroimaging fails to identify asymptomatic carriers of familial porencephaly. 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. doi: 10.1136/jmg.2005.035584, 15. The type IV collagens are encoded by six different genes (COL4A1, COL4A2, COL4A3, COL4A4, COL4A5 and COL4A6). Xia XY, Li N, Cao X, Wu QY, Li TF, Zhang C, et al. For example, networks of COL4A1 and COL4A2 are present in the basement membranes of blood vessels. This first-of-its-kind assistance program is designed for caregivers of a child or adult diagnosed with a rare disorder. doi: 10.1038/gim.2015.30, 21. While muscle cramps may begin in childhood, many of the other symptoms do not appear until later in life. Childhood presentation of COL4A1 mutations. 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. Treatment National Center for Biotechnology Information. (2008) 17:42433. In addition to providing strength and support to tissues, basement membranes provide instructional cues to cells. http://www.centerwatch.com/, For information about clinical trials conducted in Europe, contact: All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site. Acute or chronic IOP elevation can lead to glaucoma where the increased pressure damages the optic nerve causing progressive and irreversible vision loss. The COL4A1 gene provides instructions for making one component of a protein called type IV collagen. The conditions in this group have a range of signs and symptoms that involve fragile blood vessels. To use the sharing features on this page, please enable JavaScript. Curr Opin Neurol. This can occur if the carrier is a mosaic which means that some cells carry the mutation while other cells do not. 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. What does it mean if a disorder seems to run in my family? NCI CPTC Antibody Characterization Program. In: Pagon RA, Bird TD, Dolan CR, et al., GeneReviews. doi: 10.1002/ana.23736, 4. We each inherit a full complement on autosomes from each of our parents giving us two copies of each gene. Graefe's Arch Clin Exp Ophthalmol. 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. 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. 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/. Common variation in COL4A1/COL4A2 is associated with sporadic cerebral small vessel disease. (2014) 83:122834. All patients suffering from HANAC syndrome display retinal arteriolar tortuosity and occasional retinal hemorrhages. Participants with epilepsy frequently reported developmental delays (88.6%), stroke (60.0%), cerebral palsy (65.7%), and constipation (57.1%). 2018;61:765-772. Genotype-phenotype correlations in pathology caused by collagen type IV alpha 1 and 2 mutations. Mutations in the gene have been linked to diseases of the brain, muscle, kidney, eye, and cardiovascular system. Curr Opin Neurol. However, these findings can be observed independently or in combinations, in many patients with COL4A1 and COL4A2 mutations. Contact a health care provider if you have questions about your health. Common variation in COL4A1/COL4A2 is associated with sporadic cerebral small vessel disease. HANAC syndrome is characterized by angiopathy, which is a disorder of the blood vessels. Comparisons may be useful for a differential diagnosis: CADASIL is a rare genetic disorder affecting the small blood vessels in the brain. 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, . Combinations of the in silico tool MutationTaster (21) and the Alamut software (ALAMUT package, http://www.interactivebiosoftware.com, France) predicted the variant to be pathogenic as it likely alters the protein structure/function due to a detrimental effect on 112 heterotrimers formation and type IV collagen stability. 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. Still other individuals may not develop any symptoms until well into adulthood. Phone: 202-588-5700. eCollection 2021. Epub 2016 Apr 24. This condition causes mutations in genes that produce a specific type of collagen. 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. As a result, type IV collagen molecules cannot attach to each other to form the protein networks in basement membranes. No patient had cramps, cardiac symptoms, or abnormalities or Raynaud phenomenon. 2009 Jun 25 [updated 2016 Jul 7]. A diagnosis can be confirmed through molecular genetic testing.

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