Childhood presentation of COL4A1 mutations. Iannetti P, Nigro G, Spalice A, et al. EEG imaging has demonstrated that the epileptogenic zone is the dysplastic cortex, whichas it has been mentioned beforemay be situated not only within the cleft, but also in its vicinity and in the contralateral hemisphere [15, 21]. 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). Available at: https://www.ncbi.nlm.nih.gov/books/NBK7046/ Accessed January 28, 2019. Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/. The cells of the retina trigger nerve impulses that run from the optic nerve to the brain to form sight. Schizencephaly - National Institute of Neurological Urine analysis to test for blood or excess protein can be used to evaluate renal function and identify if the kidneys might be affected. The malformation was first described by Wilmarth in 1887, while in 1946, Yakovlev and Wadsworth, basing their observations on five patients with neurological deficits and brain deformations, described two types of schizencephalytype I (closed-lip), a form that does not communicate with the ventricular system, and type II (open-lip) that presents with communication with the ventricular system [5]. Barkovich AJ, Kjos BO. Language development was significantly more likely to be normal in those children with unilateral schizencephaly than in those with bilateral clefts (48% versus 6%; p < 0.002). The size and location of cerebral cavities contributes to clinical variability. In: Zakrzewski K (ed) Hydrocephalus and other disturbances of cerebro-spinal fluid circulation in children, 1st edn. Two women with schizencephaly were 22 and 64 years old. Neurology. Before COL4A1/A2-related disorders are caused by dominant mutations in the COL4A1 or COL4A2 genes. Open-type schizencephaly should be also differentiated from hydrocephalus (a case discussed in the present paper) and from holoprosencephaly. There was a history of seizures in 57% of cases, a third of which were classified as difficult to control. https://www.ncbi.nlm.nih.gov/pubmed/20558831, Alamowitch S, Plaisier E, Favrole P, et al. Seizures are relatively common, although the severity and prevalence of seizures do not appear to be dependent on the anatomical extent of involvement. https://www.clinicaltrialsregister.eu/, JOURNAL ARTICLES 7). A particular problem in differentia diagnosis is posed by open-type schizencephaly, which in medical imaging is seen as a fluid-filled space. There are no standardized treatment protocols or guidelines for affected individuals. Children with unilateral schizencephaly had a mild or moderate outcome more frequently than those with bilateral lesions (62% versus 28%; p < 0.05). March of DimesWorks to improve the health of babies by preventing birth defects and infant mortality through programs of research, community services, education, and advocacy. The NINDS Publication Catalog offers printed materials on neurological disorders for patients, health professionals, and the general public. After clearing, choose preferred Journal and select login for AAN Members. A CT scan performed immediately upon admission demonstrated bilateral extensive fluid-filled spaces in the temporal and occipital lobes, which corresponded to markedly distended temporal and occipital horns of the lateral ventricles of the brain. Given the variable expressivity of these mutations, COL4A1/A2-related disorders are likely under diagnosed and the exact number of people who have these disorders is unknown. The NINDS conducts and supports a wide range of studies that explore the mechanisms of normal brain development. Although proper interpretation of the character of intracranial fluid spaces is of significance for further therapeutic management, yet, the key decision as to the surgical intervention is made based on clinical presentation, predominantly on symptoms of intracranial hypertension. The longitudinal fissure of the brain and brain sulci are seen more clearly as compared to the preoperative scan, what indicates decreased intracranial hypertension. In keeping with the above theory, children with schizencephaly have a heterozygotic mutation of the EMX2 gene, which is a regulating gene for structural development of the prosencephalon [15]. 3 and and44). Schizencephaly | Encyclopedia.com WebYour childs outlook and life expectancy depend on how severe their condition is. ADVERTISEMENT: Radiopaedia is free thanks to our supporters and advertisers. TTY: (866) 411-1010 Problems with growth in the womb can cause partial agenesis of the corpus callosum where there are fewer nerves or complete agenesis that leads to a missing corpus callosum.. Autosomal Dominant Familial Porencephaly Type I. Sarnat HB. The present life expectancy in Germany for men is 75.6 years and for women it is 81.3 years. Submit only on articles published within 6 months of issue date. Date 06/2024. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site. Diagnostic neuroradiology. The Chen H (2006) Schizencephaly. Common variation in COL4A1/COL4A2 is associated with sporadic cerebral small vessel disease. (For instructions by browser, please click the instruction pages below). Some may only develop specific symptoms such as isolated migraines or strokes in childhood or adulthood. You will be redirected to a login page where you can log in with your AAN ID number and password. September 2003. 1988;150 (6): 1391-6. Schizencephaly is a rare cerebral malformation with an estimated incidence of 0.54 to 1.54 per 100,000 live births. The effect of the treatment was a resolution of symptoms of intracranial hypertension, which is a direct life-threatening condition and requires a prompt intervention. WebMD does not provide medical advice, diagnosis or treatment. Agenesis of the Corpus Callosum: Causes, Treatments, and Aim To evaluate survival, clinical, and genetic characteristics of all patients with classic or type 1 lissencephaly born between 1972 and 1990 in the Netherlands, Schizencephaly with occlusion or absence of middle cerebral artery. A follow-up scan, 3years after shunt implantation: considerable regression of the bilateral arachnoid cysts in the middle cranial fossa. Go to: 2. It connects the right brain to the left brain and helps them communicate with each other. The scan was performed as an emergency procedure in a patient with severe and growing in intensity symptoms of intracranial hypertension, what did not allow for extensive, time-consuming diagnostic management. Schizencephaly is an uncommon congenital disorder of cerebral cortical development. In the majority of cases, in this location, arachnoid cysts are seen. COL4A1/A2-related disorders can also be associated with a variety of abnormalities affecting the front or back of the eyes. Both methods are associated with a risk of such complications as postoperative bleeding, distension of the paracerebral fluid spaces forming subdural hygromas or hygro-hematomas, empyemas, meningitis, and hydrocephalus. The management of COL4A1/A2-related disorders may require the coordinated efforts of a team of specialists. In affected individuals who exhibit infantile spasms, onset of these sudden, involuntary contractions tends to occur within the first six months of life. Neurology. Agenesis of the corpus callosum (ACC) is a brain disorder in which the tissue that connects the left and right sides of the brain (its hemispheres) is partially or completely missing. Absence of the Cavum Septum Pellucidum In most people, small vessel disease in the brain does not cause symptoms. Some patients with unilateral clefts may only ischemia). 1275 Mamaroneck AvenueWhite Plains, NY 10605askus@marchofdimes.comhttp://www.marchofdimes.comTel: White PlainsFax: 914-428-8203, National Dissemination Center for Children with Disabilities, U.S. Dept. 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. In view of the clinical symptoms of intracranial hypertension, the child was implanted a cysto-ventriculoperitoneal shunt (Fig. In a healthy brain, nerve fibers in the corpus callosum grow as your child gets older. CT is also useful, but to a lesser degree, since it provides poorer images of the gray matter, which are the key factor in differentiating between the malformation and other fluid-associated CNS abnormalities. On the other hand, schizencephaly itself and its associated symptoms are treated conservatively. Forty-three patients (91%) had associated cerebral developmental anomalies, most commonly absence of the septum pellucidum (45%) and focal cortical dysplasia (40%). Some familial cases have been reported, in which case, heterozygous germline mutations of the homeobox gene EMX2 are often encountered 6. 2009;73:1873-1882. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2881859/, Mao, M, Alavi MV, Labelle-Dumais, C, Gould DB. Schizencephaly is a rare cortical malformation that manifests as a grey matter lined cleft extending from the ependyma to the pia mater. Schizencephaly life expectancy | HealthTap Online Doctor Web page addresses and e-mail addresses turn into links automatically. National Center for Biotechnology Information In addition to the effects of a clear COL4A1 or COL4A2 mutation, large genetic studies reported associations for COL4A1/A2 with intracranial aneurysms, myocardial infarction, arterial calcification, arterial stiffness, deep intracerebral hemorrhages, lacunar ischemic stroke, reduced white matter volume and vascular leukoencephalopathy. 2012;322:25-30. https://www.ncbi.nlm.nih.gov/pubmed/22868088, Shah S, Ellard S, Kneen R, et al. In this case, the employed modality addressed acute intracranial hypertension rather than schizencephaly itself. The prognosis for individuals with schizencephaly varies depending on the size of the clefts and the extent of neurological disabilities. The two genes that code for these proteins are tightly linked on chromosome 13 and dominant COL4A1 and COL4A2 gene mutations cause a highly variable, multisystem disorder. NORD strives to open new assistance programs as funding allows. We have changed the login procedure to improve access between AAN.com and the Neurology journals. This means there is often not much information known about the disorder and doctors and researchers do not see enough patients with it. As it followed from her medical history, the mother had had a toxoplasma infection in pregnancy. Following implantation of a drain system and clinical improvement of the patient, a MRI scan of the head was performed, which ultimately confirmed that the fluid-filled spaces in the two middle cranial fossae corresponded to arachnoid cysts. Neurodevelopmental outcome was generally poor, with 51% of patients (24/47) having severe deficits, 32% of patients (15/47) having moderate impairment, and 17% of patients (8/47) having mild or no problems. Amirsys Publishing, Inc. Chapter 1 pp77-80. What is the Outlook for People with Agenesis of the Corpus Callosum? Genetic Causes of Polymicrogyria A 1-month-old girl admitted to the Cracow University Childrens Hospital of Krakow with suspected intracranial hypertension and diagnosed epilepsy. Nonenhanced CT scan. Some of the patient advocacy organizations listed in the Resources section below provide support and information to affected individuals and their families. Children inherit a full complement of chromosomes from each of their parent and so we carry two copies of each gene. Brant WE, Helms CA. You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid Osborn AG. The fluid-filled spaces were still present; albeit markedly smaller as compared to the initial scan, discrete asymmetry of the lateral ventricles persisted, but no displacement of the lateral fissure of the brain was detected. (2008) ISBN:0444518967. Children who had involvement of a single lobe accounted for 88% of those with mild outcomes and 53% of those with moderate outcomes. 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. The following organizations and resources help individuals, families, friends, and caregivers of people living withACC: Genetic and Rare Diseases (GARD) Information Center, National Organization for Disorders of the Corpus Callosum 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. It is almost always sporadic, although a few familial cases have been described 6. Schizencephaly means split brain. The brain has one or more clefts or splits lined with clumps of misplaced cells (heterotopia), cells that dont fold as they should (polymicrogyria) or a combination of both. Schizencephalydiagnostics and clinical dilemmas - PMC The advocates of the theory are of the opinion that other malformations, which may present concomitantly with schizencephaly, such as polymicrogyria, agenesis of the septum pellucidum and/or corpus callosum, optic nerve atrophy, arachnoid cysts, and cerebellar anomalies, provide an argument in support of the genetic background of schizencephaly [16]. DOI: https://doi.org/10.1212/WNL.48.5.1427, Neurology: Neuroimmunology & Neuroinflammation, 1997 by the American Academy of Neurology. Some of these patients have been described as having HANAC syndrome, which is an acronym for hereditary angiopathy, nephropathy, aneurysms, and muscle cramps. Individuals with COL4A1/A2-related disorders have characteristic patterns of brain disease when viewed under advanced imaging techniques. Eur J Med Genet. The features on CT are the same as on MRI (see below) but merely less well visualized. A blood trace along the tentorium of the cerebellum. 'MacMoody'. If your baby has other brain irregularities that might mean they need lifelong medical care, your doctor will refer you to a specialist. Phone: 617-249-7300, Danbury, CT office Classification system for malformations of cortical development. In addition to porencephaly there can be other forms of damage to the brain present at birth. Phone: 203-744-0100 Schizencephaly: association with young maternal age, alcohol use, and lack of prenatal care. Hum Mol Genet. If your doctor sees any brain changes during your routine pregnancy scans, they might order extra testing to verify a diagnosis. Schizencephaly - Wikipedia Some children learn normally but have neurological symptoms. We report the clinical and cranial imaging features of 47 children with unilateral open-lip (171, unilateral closed-lip (121, bilateral open-lip (121, and bilateral closed-lip (6) schizencephaly, as defined radiologically. Plaisier E, Ronco P. COL4A1-Related Disorders. A Podcast For The Rare Disease Community, Rare Disease Cures Accelerator (RDCA-DAP), Policy Statements & Letters to Policymakers, Stay Informed With NORDs Email Newsletter, Launching Registries & Natural History Studies, https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282239/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5328961/, https://www.ncbi.nlm.nih.gov/pubmed/28254515, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728690/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4351667/, https://www.nature.com/articles/gim2014210, https://www.ncbi.nlm.nih.gov/pubmed/23225343, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3459649/, https://www.ncbi.nlm.nih.gov/pubmed/22868088, https://www.ncbi.nlm.nih.gov/pubmed/22574627, https://www.ncbi.nlm.nih.gov/pubmed/20558831, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2881859/, https://www.ncbi.nlm.nih.gov/pubmed/26610912, https://www.ncbi.nlm.nih.gov/books/NBK7046/, https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Cephalic-Disorders-Fact-Sheet, https://rarediseases.org/patient-assistance-programs/medicalert-assistance-program/, https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/, https://rarediseases.org/patient-assistance-programs/caregiver-respite/, Learn more about Patient Assistance Programs >, Arginine: Glycine Amidinotransferase Deficiency, https://rarediseases.org/non-member-patient/epilepsy-foundation/, Gould Syndrome Foundation (COL4a1/COL4A2), https://rarediseases.org/non-member-patient/gould-syndrome-foundation-col4a1-col4a2/, https://rarediseases.org/non-member-patient/national-kidney-foundation/, https://rarediseases.org/non-member-patient/nih-national-eye-institute/, NIH/National Institute of Neurological Disorders and Stroke, Aromatic L-Amino Acid Decarboxylase Deficiency, https://rarediseases.org/non-member-patient/nih-national-institute-of-neurological-disorders-and-stroke/, https://rarediseases.org/non-member-patient/the-arc/, Learn more about Patient Organization & Membership >, HANAC: hereditary angiopathy, nephropathy and cramps syndrome (OMIM #611773), POREN1: autosomal dominant type 1 porencephaly; porencephaly with infantile hemiplegia (OMIM #175780, RATOR: retinal arterial tortuosity (OMIM #180000), BSVD: brain small vessel disease with or without ocular anomalies (OMIM #607595), ICH: susceptibility to intracerebral hemorrhage (OMIM #614519). Babies with clefts in both hemispheres (called bilateral clefts) commonly have developmental delays, delays in speech and language skills, and problems with brain-spinal cord communication. Schizencephaly, a specific pattern of PMG that describes a full-thickness cleft in the brain lined by PMG. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282239/. 2017;57-58:29-44. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5328961/, Sondergaard CB, Nielsen JE, Hansen CK, Christensen H. Hereditary cerebral small vessel disease and stroke. Dev Med Child Neurol. Persistent supratentorial fluid-filled spaces of a comparable size. The https:// ensures that you are connecting to the In the present paper, the authors described difficulties in employing diagnostic imaging in differentiating between type II (open-lip) schizencephaly and much more common intracranial fluid spaces of a different origin (arachnoid cysts and hydrocephalus). 4. The disorder is usually apparent at birth (congenital) or early in life, based upon characteristic physical findings and specialized imaging tests. NORD and MedicAlert Foundation have teamed up on a new program to provide protection to rare disease patients in emergency situations. The abnormality is increasingly detected at the antenatal ultrasound, especially when it is of the open-lip variety. More guidelines and information on Disputes & Debates, Involvement of Type I Interferon Signaling in Muscle Stem Cell Proliferation During Dermatomyositis, Neurology | Print ISSN:0028-3878 January 31, 2019 Treatment The first reports of human COL4A1 mutations were in patients with autosomal dominant porencephaly and a more recent study found that COL4A1 mutations were found in ~16% of patients with porencephaly. No, I did not find the content I was looking for, Yes, I did find the content I was looking for, Please rate how easy it was to navigate the NINDS website, National Organization for Disorders of the Corpus Callosum, Delays in attaining developmental milestones such as walking, talking, or reading, Clumsiness and poor motor coordinationparticularly with skills that require coordination of left and right hands and feet, such as swimming, bicycle riding, and driving, Problems with mental and social processing, Impairment in social interaction and communication that may overlap with. In Zakrzewski K (ed) Hydrocephalus and other disturbances of cerebro-spinal fluid circulation in children, 1st ed. Aura refers to additional neurological symptoms that occur with, or sometimes before, the development of the migraine headache. 10). Whether this is from an in-utero insult or the expression of genetic factors is unclear. A similar term, variable expressivity, describes when affected individuals have widely varying signs and symptoms. In general developmental delay, motor disturbance correlates with the degree of anatomical abnormality, especially when clefts are present bilaterally. Nonenhanced CT scan, The photo presents the same scan as in Fig. Mosby Inc. (1994) ISBN:0801674867. 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. COL4A1/A2-related disorders are dominant genetic disorders. A cleft extends from the ependymal surface of the brain to the pia mater, and the two layers meet in the cleft: the so-called pial-ependymal seam 5. The site is secure. Children with closed-lip schizencephaly presented with hemiparesis or motor delay whereas patients with open-lip schizencephaly presented with hydrocephalus or seizures. The most differentiating important element in imaging studies is the presence of heterotrophic gray matter that lines the margins of the cleft in case of schizencephaly and absence of such a lining in arachnoid cysts or fluid-filled spaces with other background. The defect is characterized by the presence of a cleft in the brain extending from the surface of the pia mater to the cerebral ventricles. Nonenhanced CT scan. Donnelly, Lane F. (2009). They are especially related to early, in utero injuries to the brain. Online ISSN:1526-632X, The most widely read and highly cited peer-reviewed neurology journal, Correlations of clinical and radiologic features. INTERNET 55 Kenosia Avenue When an individual tests positive for a mutation but does not manifest the effects, it is referred to as having incomplete or reduced penetrance. and apply to letter. Migraines can occur with or without aura. If you are responding to a comment that was written about an article you originally authored: Barkovich AJ, Norman D. MR imaging of schizencephaly. However, there are exceptions that depend on precisely when and where the mutation arose. Nonenhanced CT scan. In rare instances of arachnoid cysts, thinning and bulging of cranial bones are seen in areas where they adhere to the cyst. Advanced imaging techniques can include computerized tomography (CT) scanning and magnetic resonance imaging (MRI). Schizencephaly COL4A1/A2-related disorders follow an autosomal dominant pattern of inheritance. This makes it hard to learn from them through observations or large studies. The margins of the cleft are lined with heterotrophic, dysplastic gray matter. Pay-per-view content is for the use of the payee only, and content may not be further distributed by print or electronic means. (Exception: original author replies can include all original authors of the article). 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. However, associated problems can be life-threatening. Schizencephaly Life expectancy is a hypothetical measure. The population of many of the richest countries in the world have life expectancies of over 80 years. official website and that any information you provide is encrypted 1825 K Street, NWSuite 1200Washington, DC 20006Info@thearc.orghttp://www.thearc.orgTel: WashingtonFax: 202-534-3731. In case of unilateral schizencephaly, 60% are open [4, 9, 10]. A follow-up scan 8months following shunting. The networks formed by the COL4A1 and COL4A2 proteins are called basement membranes and are present in every organ of the body. The etiopathogenesis of schizencephaly has not been fully elucidated. Phone:714-747-0063, Form Approved OMB# 0925-0648 Exp. It transfers and integrates information, which is vital for learning. CT can adequately visualize open lip schizencephaly, as well as substantial heterotopic grey matter, but due to an inherent limited ability to distinguish grey from white matter, it is not ideal for fully characterizing congenital abnormalities. Ketonen L, Hiwatashi A, Sidhu R. Pediatric brain and spine, an atlas of MRI and spectroscopy. These types of correlations can be difficult to detect in patients because of the broad genetic variability in humans. This study clearly demonstrates that COL4A1 and COL4A2 mutations cause clinically variable cerebrovascular disease that includes characteristic features of cerebral small vessel disease. Wydawnictwo Czelej Sp. The risk of passing the non-working gene from an affected parent to an offspring is 50% for each pregnancy. Most children with agenesis of the corpus callosum have a long and fulfilling life. schizencephaly WebAlthough the spasms usually go away by the time a child is 4 years old, many babies with IS will have other kinds of epilepsy later in life. Children are likely to have other conditions, including: The corpus callosum helps both sides of your brain communicate with each other. 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. The ultimate goal of IAMRARE is to unite patients and research communities in the improvement of care and drug development. Merello E, Swanson E, De Marco P, et al. Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment. Other risk factors of schizencephaly development include also maternal young age (below 20years of life), no prenatal medical care (especially in the first trimester of pregnancy), and abuse of alcohol and narcotic substances as well as using some medications by pregnant women (e.g., warfarin). Medical imaging shows schizencephaly as a linear cleft lined with heterotrophic gray matter and extending from the cortical surface to the ventricular system. Others have more serious learning disabilities., Some common learning delays include problems with:. Coexistence of schizencephaly and intracranial arteriovenous malformation in an infant. https://www.ncbi.nlm.nih.gov/pubmed/26610912. 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. Non-AAN Member subscribers (800) 638-3030 or (301) 223-2300 option 3, select 1 (international) Some authors do not use the term schizencephaly,preferring to group these disorders under the blanket term of porencephaly. In addition, CT showed a minimal mass effect manifested as displacement of the longitudinal fissure of the brain to the right and compression and stenosis of the left lateral cerebral ventricle, as well as mild thinning of the squama of the temporal bone at the level of the malformation (Figs. Hence, failure to detect the CSP prior to 18 weeks or after 37 weeks should be considered a normal finding 7,8. Porencephaly/Cystic Encephalomalacia - Child Neurology The signs and Patients with closed-lip schizencephaly were more likely to have a mild to moderate outcome than those with open-lip type (78% versus 31%; p < 0.05). The most common location of the anomaly is the frontal lobe and the region of the lateral sulcus [14]. If we dont have a program for you now, please continue to check back with us. Schizencephaly is an extremely rare developmental birth defect characterized by abnormal slits, or clefts, in the cerebral hemispheres of the brain.
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