Oral expression was reduced and neuropsychological testing revealed language delay with a prominent expression deficit. At least 50 individuals with this condition have been described in the scientific literature. 2011 Supporting children in their development to reduce handicaps and combining their follow-up with parent counseling could be considered as an ideal approach. MedlinePlus also links to health information from non-government Web sites. Porencephaly refers to the formation of fluid-filled cysts or cavities within of the brain. Maybe try a search? Various muscles can be affected and muscle strength can become weakened. Arch Ophthalmol. The COL4A1 gene provides instructions for making one component of a protein called type IV collagen. 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. No patient had cramps, cardiac symptoms, or abnormalities or Raynaud phenomenon. 1900 Crown Colony Drive Type IV collagen molecules attach to each other to form complex protein networks. Exome sequencing in 32 patients with anophthalmia/microphthalmia and developmental eye defects. 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 Suggestive evidence for linkage to chromosome 13qter for autosomal dominant type 1 porencephaly. When this enzyme is elevated, it is a sign of muscle damage. When an individual tests positive for a mutation but does not manifest the effects, it is referred to as having incomplete or reduced penetrance. 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. Zeeva is one of fewer than 150 people in the world with a rare disease called Gould Syndrome or COL4A1/A2. With input from doctors, researchers, and the US Food & Drug Administration, NORD has created IAMRARE to facilitate patient-powered natural history studies to shape rare disease research and treatments. National Center for Biotechnology Information. (2014) 34:757. For example, networks of COL4A1 and COL4A2 are present in the basement membranes of blood vessels. 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. Neurologic phenotypes associated with COL4A1/2 mutations: expanding the spectrum of disease. Phenotypic spectrum of COL4A1 mutations: porencephaly to schizencephaly. 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. PMC However, there are exceptions that depend on precisely when and where the mutation arose. For example, an individual may carry genetic variants elsewhere in their genome that confers protection or susceptibly to the mutation and environmental experiences (trauma, anticoagulant use, physical exertion etc.) Gould Syndrome is an ultra rare genetic, multi-system disorder. We connect and coordinate our families with researchers and medical professionals to get our disease and management coordination into the medical realm. COL4A1 mutations as a monogenic cause of cerebral small vessel disease: a systematic review. In the front of the eye, patients can have abnormally small eyes (microphthalmia), cataracts (cloudy lenses), and anterior segment dysgenesis (Axenfeld-Rieger). Sci Rep. 2016;6:18602. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728690/, Rannikmae K, Davies G, Thomson PA, et al. Please note that NORD provides this information for the benefit of the rare disease community. Doctors and researchers to bring research and medical therapeutic options to those affected. See our, COL4A1-related brain small-vessel disease, URL of this page: https://medlineplus.gov/genetics/condition/col4a1-related-brain-small-vessel-disease/. It is passed through families in a autosomal dominant fashion. Lanfranconi S, Markus HS. Probands' father had severe hypermetropia and bilateral cataracts. The https:// ensures that you are connecting to the Recent findings: Illumina's Sequencing by Synthesis (SBS) technology (MiSeq Personal Sequencer, Illumina) analyzed the generated amplicons. Pediatricians are physicians who specialize in the childhood disorders and are often the first to detect patients with COL4A1/A2-related disorders. http://www.centerwatch.com/, For information about clinical trials conducted in Europe, contact: For asymptomatic patients, cerebral and vessel imaging for aneurysm screening and ophthalmologic follow-up are indicated (2). Prenatal clinical manifestations in individuals with COL4A1/2 variants. The severity of the condition varies greatly among affected individuals. The expanding phenotype of COL4A1 and COL4A2 mutations: clinical data on 13 newly identified families and a review of the literature. 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. J Neurol Sci. Genetic counseling will be proposed when IV-3 and IV-6 intend to start a family as there is a 50% risk of mutation transmission to the next generation and potential obstetrical complications. Mutations in the gene have been linked to diseases of the brain, muscle, kidney, eye, and cardiovascular system. Urine analysis to test for blood or excess protein can be used to evaluate renal function and identify if the kidneys might be affected. Gould Syndrome - COL4A1 - COL4A2 genes - Gould Syndrome Foundation Gould Syndrome Foundation 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. Keywords: COL4A1, Type IV collagen, familial porencephaly, ocular malformations, variable expressivity, Citation: Scoppettuolo P, Ligot N, Wermenbol V, Van Bogaert P and Naeije G (2020) p.Gly743Val Mutation in COL4A1 Is Responsible for Familial Porencephaly and Severe Hypermetropia. In the brain, intracerebral hemorrhage is the most frequent phenotype. Since fewer than 100 families have been reported, the exact prevalence of COL4A1-related disorders is not well-established. Jeanne M, Gould DB. Berg R, Aleck A, Kaplan A. Familial porencephaly. doi: 10.1038/gim.2014.210, 3. The causative gene of HANAC is COL4A1 (13q34) encoding the alpha1 chain of collagen IV, a major component of basement membranes also involved in . CADASIL patients can experience progressive memory loss, deterioration of intellectual abilities and loss of balance with a progressive worsening of these symptoms, but symptoms are usually less severe and occur later in life. To use the sharing features on this page, please enable JavaScript. Eur J Paediatr Neurol. Resource(s) for Medical Professionals and Scientists on This Disease: People with this condition may have a bulge in one or multiple blood vessels in the brain (intracranial aneurysms). Vahedi K, Alamowitch S. Clinical spectrum of type IV collagen (COL4A1) Hereditary cerebral small vessel diseases: a review. 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. Stroke subtype, vascular risk factors, and total MRI brain small-vessel disease burden. (2010) 75:7479. Next generation sequencing uncovers a missense mutation in COL4A1 as the cause of familial retinal arteriolar tortuosity. Molecular Dynamics Investigation on the Effects of Protonation and Lysyl Hydroxylation on Sulfilimine Cross-links in Collagen IV. The X and Y chromosomes are called the sex chromosomes and the rest all are called 'autosomes'. COL4A1 and COL4A2 are on Chr. He smiled, caught it, and asked Zeeva if he could throw it back. doi: 10.1111/j.1469-8749.2011.04198.x, 26. What is the prognosis of a genetic condition? Ensuring that patients and caregivers are armed with the tools they need to live their best lives while managing their rare condition is a vital part of NORDs mission. 2009 Jun 25 [Updated 2016 Jul 7]. 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. NORD gratefully acknowledges Douglas Gould, PhD, Professor, Director of Research, Denise B. Evans Endowed Chair in Ophthalmology, Departments of Ophthalmology and Anatomy, Institute for Human Genetics, University of California San Francisco School of Medicine, and the COL4A1 Foundation, for assistance in the preparation of this report. CADASIL is an acronym that stands for: (C)erebral relating to the brain (A)utosomal (D)ominant a form of inheritance in which one copy of an abnormal gene is necessary for the development of a disorder (A)rteriopathy disease of the arteries (blood vessels that carry blood away from the heart) (S)ubcortical relating to specific areas of the brain supplied by deep small arteries (I)nfarcts tissue loss in the brain caused by lack of blood flow to the brain, which occurs when circulation through the small arteries is severely reduced or interrupted (L)eukoencephalopathy lesions in the brain white matter caused by the disease and observed on MRI. Mosaicism can contribute to both reduced penetrance or variable expressivity but other factors do as well. In: Pagon RA, Bird TD, Dolan CR, et al., GeneReviews. 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. doi: 10.1001/archophthalmol.2010.42, 10. 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). 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: