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European Review For Medical and... Jan 2021This article aimed to describe a novel COL4A2 mutation and the phenotypic features of two family members presenting with epilepsy and cortical development malformations.
OBJECTIVE
This article aimed to describe a novel COL4A2 mutation and the phenotypic features of two family members presenting with epilepsy and cortical development malformations.
PATIENTS AND METHODS
The first patient is a 65-year-old woman with hematuria and adult-onset seizures. Brain MRI showed closed lip schizencephaly of right lateral sulcus associated with polymicrogyria of the surrounding cortex and areas of subcortical heterotopia. The second patient is a 40-year-old man, her son. He was born post-term with neonatal distress and psychomotor developmental delay with congenital left leg paresis and strabismus, as well as childhood-onset focal motor seizures. Brain MRI showed a right nucleus-capsular porencephalic cavitation with enlargement of the homolateral ventricle and a focal right occipital cortico-subcortical encephalomalacia. A small heterotopic band was also present in the frontal left subcortical region.
RESULTS
We tested both patients with a NGS panel for genetic epilepsies, which evidenced a missense mutation in COL4A2 gene (c.2972G>A, causing the aminoacidic substitution Gly991Glu).
CONCLUSIONS
The phenotypic spectrum associated with COL4A2 mutations has not been extensively described in the literature. Testing for COL4A mutations is indicated in patients with malformations of cortical development, particularly in the presence of familial conditions, even in the absence of porencephaly or early hemorrhagic strokes.
Topics: Adult; Aged; Collagen Type IV; Female; Hemangioma, Cavernous, Central Nervous System; Humans; Magnetic Resonance Imaging; Male; Malformations of Cortical Development; Mutation
PubMed: 33577044
DOI: 10.26355/eurrev_202101_24658 -
Ultrasound in Obstetrics & Gynecology :... May 2021To establish the prevalence of COL4A1 and COL4A2 gene mutations in fetuses presenting with a phenotype suggestive of cerebral injury.
OBJECTIVE
To establish the prevalence of COL4A1 and COL4A2 gene mutations in fetuses presenting with a phenotype suggestive of cerebral injury.
METHODS
This was a single-center retrospective analysis of all cases of fetal cerebral anomalies suggestive of COL4A1 or COL4A2 gene mutation over the period 2009-2018. Inclusion criteria were: (1) severe and/or multifocal hemorrhagic cerebral lesions; (2) multifocal ischemic-hemorrhagic cerebral lesions. These anomalies could be of different ages and associated with schizencephaly or porencephaly. Between fetuses with and those without a mutation, we compared gestational age at the time of diagnosis, parity and fetal gender.
RESULTS
Among the 956 cases of cerebral anomaly diagnosed in our center during the 10-year study period, 18 fetuses were identified for inclusion. A pathogenic COL4A1 gene mutation was found in five of these cases, among which four were de-novo mutations. A variant of unknown significance was found in four fetuses: in the COL4A1 gene in one case and in the COL4A2 gene in three cases. No COL4A1 or COL4A2 mutation was found in the remaining nine fetuses. The median (interquartile range) gestational age at diagnosis was significantly lower in cases with a mutation (24 (22-26) weeks) than in cases without a mutation (32 (29.5-34.5) weeks) (P = 0.03).
CONCLUSIONS
A phenotype suggestive of cerebral injury was found in 18 of the 956 (1.9%) cases in our population, in 28% of which there was an associated COL4A1 or COL4A2 mutation. COL4A1 and COL4A2 gene mutations should be sought systematically in cases of severe and/or multifocal hemorrhagic or ischemic-hemorrhagic cerebral lesions, with or without schizencephaly or porencephaly. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Adult; Cerebral Hemorrhage; Collagen Type IV; Female; Gestational Age; Humans; Malformations of Cortical Development; Mutation; Phenotype; Porencephaly; Pregnancy; Pregnancy Outcome; Prenatal Diagnosis; Prevalence; Retrospective Studies; Schizencephaly
PubMed: 32515830
DOI: 10.1002/uog.22106 -
Epilepsia Dec 2014Cortical resections in epilepsy surgery tend to be larger in children, compared to adults, partly due to underlying pathology. Some children show unilateral multifocal...
OBJECTIVE
Cortical resections in epilepsy surgery tend to be larger in children, compared to adults, partly due to underlying pathology. Some children show unilateral multifocal seizure onsets involving much of the hemisphere. If there were a significant hemiparesis present, hemispherectomy would be the procedure of choice. Otherwise, it is preferable to spare the primary sensorimotor cortex. We report the results of "subtotal" hemispherectomy in 23 children.
METHODS
All children (ages 1 year and 4 months to 14 years and 2 months) were operated on between 2001 and 2013 at Children's Hospital of Michigan (Detroit). Patients were evaluated with scalp video-electroencephalography (EEG), magnetic resonance imaging (MRI), (18) F-fluorodeoxyglucose-positron emission tomography (FDG-PET) scans, and neuropsychological assessments when applicable. Subsequently, each case was discussed in a multidisciplinary epilepsy surgery conference, and a consensus was reached pertaining to candidacy for surgery and optimum surgical approach. The actual extent of resection was based on the results from subdural electrocorticography (ECoG) monitoring. The surgical outcome is based on International League Against Epilepsy (ILAE) classification (class 1-6).
RESULTS
Among the 23 patients, 11 had epileptic spasms as their major seizure type; these were associated with focal seizures in 3 children. MRI showed focal abnormalities in 12 children. FDG-PET was abnormal in all but one subject. All except two children underwent chronic subdural ECoG. Multiple subpial transections were performed over the sensorimotor cortex in three subjects. On histopathology, various malformations were seen in 9 subjects; the remainder showed gliosis alone (n = 12), porencephaly (n = 1), and gliosis with microglial activation (n = 1). Follow-up ranged from 13 to 157 months (mean = 65 months). Outcomes consisted of class 1 (n = 17, 74%), class 2 (n = 2), class 3 (n = 1), class 4 (n = 1), and class 5 (n = 2).
SIGNIFICANCE
Extensive unilateral resections sparing only sensorimotor cortex can be performed with excellent results in seizure control. Even with the presence of widespread unilateral epileptogenicity or anatomic/functional imaging abnormalities, complete hemispherectomy can often be avoided, particularly when there is little hemiparesis.
Topics: Adolescent; Child; Child, Preschool; Electroencephalography; Epilepsies, Partial; Female; Fluorodeoxyglucose F18; Hemispherectomy; Humans; Infant; Longitudinal Studies; Magnetic Resonance Imaging; Male; Positron-Emission Tomography; Retrospective Studies; Treatment Outcome
PubMed: 25366422
DOI: 10.1111/epi.12845 -
Acta Veterinaria Hungarica Jun 2023Congenital malformations occur sporadically in cattle; however, congenital structural and functional disorders of the nervous system are rather common in ruminants....
Congenital malformations occur sporadically in cattle; however, congenital structural and functional disorders of the nervous system are rather common in ruminants. Among the numerous causes of congenital nervous system defects, infectious agents are highlighted in this paper. Virus-induced congenital malformations are well known, among which those caused by bovine viral diarrhoea virus (BVDV), Akabane virus (AKAV), Schmallenberg virus (SBV), Bluetongue virus (BTV), and Aino virus (AV) are the most studied. In this study, we specify and categorise macroscopic and histopathological lesions in the brain of 42 newborn calves suffering from severe neurologic signs and diagnosed with BVDV and AKAV infection. Following a complete necropsy, specimens were collected from the brains to track the presence of BVDV, AKAV and SBV utilising reverse transcription polymerase chain reaction. Of the 42 examined calves, 21 were BVDV positive and 6 were AKAV positive, while 15 brains were negative for the studied agents. Regardless of the aetiology, cerebellar hypoplasia, hydranencephaly, hydrocephalus, porencephaly, and microencephaly were detected. Cerebellar hypoplasia was the most common lesion seen in both BVDV-positive and AKAV-positive cases. Virus-induced necrosis of the germinative cells of the external granular layer of cerebellum, as well as vascular damages, are believed to be the underlying causes of cerebellar hypoplasia. BVDV was the most important aetiological agent of such cases in this study.
Topics: Animals; Cattle; Animals, Newborn; Bunyaviridae Infections; Cerebellum; Ruminants; Diarrhea; Bovine Virus Diarrhea-Mucosal Disease
PubMed: 37104096
DOI: 10.1556/004.2023.00764 -
The Journal of the Association of... May 2023
Topics: Humans; Aged; Porencephaly; Brain Diseases; Brain
PubMed: 37355830
DOI: No ID Found -
JFMS Open Reports 2022A 6-week-old entire female domestic shorthair cat was presented for evaluation of a soft bulge and a palpable skull defect on the forehead, present since adoption a few...
CASE SUMMARY
A 6-week-old entire female domestic shorthair cat was presented for evaluation of a soft bulge and a palpable skull defect on the forehead, present since adoption a few days earlier. The neurological examination revealed an absent menace response bilaterally and apparent blindness, localising the lesion to the occipital cortex. The main differential diagnoses were meningocoele (MC) and meningoencephalocoele (MEC). Surgical repair was proposed once the cat reached adult size. Meanwhile, the cat developed seizures and was treated with anticonvulsant therapy. At 6 months of age, CT confirmed a frontoparietal MEC with associated porencephaly. Based on a three-dimensional printed skull mould, a polysulfone implant was created. The meninges were dissected from the skin, a durectomy was performed and samples of the protruding brain were obtained. Part of the cerebrospinal fluid was drained until the size of the protruding brain decreased enough to be included below the implant that was anchored on top of the skull with cerclages. Histopathology confirmed the diagnosis of MEC. Three years and 7 months later, the cat had partially recovered vision but continued to seize monthly despite antiepileptic drugs.
RELEVANCE AND NOVEL INFORMATION
MC/MEC is a relatively uncommon disease reported in companion animals, and only four cases of surgical management have been described, and did not use a polysulfone tailor-made implant. In human medicine, surgical intervention is the treatment of choice. This case highlights a new implant option for surgical correction of MEC with good long-term result and no complications after 3 years and 7 months.
PubMed: 35693478
DOI: 10.1177/20551169221098940 -
Diagnostics (Basel, Switzerland) Nov 2022(SC) is a species of belonging to the group, along with and . Despite its commensal nature, underlying risk factors and medical conditions might lead to various...
(SC) is a species of belonging to the group, along with and . Despite its commensal nature, underlying risk factors and medical conditions might lead to various anatomic site infections caused by this opportunistic pathogen. Although SC infections have mostly been associated with bacteremia, some case reports of abscess and empyema formation have been documented. Herein, we report a case of a middle-aged female patient who initially presented with radiculopathy symptoms. Subsequent neurologic imaging revealed a pyogenic abscess along paravertebral muscles, which was found to be caused by SC. The patient was successfully treated with abscess drainage from the lumbar zone and antibiotics, and the symptoms of radiculopathy have completely resolved.
PubMed: 36359529
DOI: 10.3390/diagnostics12112686 -
Acta Virologica 2019Schmallenberg virus (SBV), a neurotropic member of the genus Orthobunyavirus, infects ruminants and causes neurological lesions and fetal malformations including...
Schmallenberg virus (SBV), a neurotropic member of the genus Orthobunyavirus, infects ruminants and causes neurological lesions and fetal malformations including cerebellar hypoplasia, hydranencephaly, and porencephaly. The aim of this study is to establish intracerebral (i.c.) infection of SBV in newborn BALB/c mice and to investigate some of the transcription factors in brain. For this aim, brain samples of newborn BALB/c mice which were infected with SBV i.c. were analyzed by plaque titration and real-time RT-PCR for T-bet, Gata3, RoRγt, Foxp3 and Eomes mRNA levels. Study results showed that SBV can replicate in BALB/c mice brain and cause death of newborn mice with generation of infectious viral particles. Analyses of transcription factor mRNA levels indicated up-regulation of T-bet, Gata3, RoRγt, Foxp3 and down-regulation of Eomes. In this report, we introduce preliminary data of T cell transcription factors affected by SBV infection of BALB/c mice. Keywords: Eomes; Foxp3; Gata3; RoRγt; Schmallenberg virus; T-bet.
Topics: Animals; Animals, Newborn; Brain; Bunyaviridae Infections; Gene Expression Regulation; Mice; Mice, Inbred BALB C; Orthobunyavirus; RNA, Messenger; Ruminants; Transcription Factors; Virus Replication
PubMed: 31507194
DOI: 10.4149/av_2019_306 -
BMJ Case Reports Feb 2024Gould syndrome is an autosomal dominant syndrome due to a COL4A1 or COL4A2 mutation that is commonly characterised by familial porencephaly, seizures, intracranial...
Gould syndrome is an autosomal dominant syndrome due to a COL4A1 or COL4A2 mutation that is commonly characterised by familial porencephaly, seizures, intracranial haemorrhages, cataracts, nephropathies and more. There have been up to 137 identified patients based on a review of the literature. In this case, we describe a male infant that presents with hemiparesis, developmental delay and gait abnormalities at his well-child check. Referral to neurology and a subsequent MRI demonstrated porencephaly and ocular lens abnormalities. Genetic sequencing uncovered a mutation to the COL4A1 gene, suggesting Gould syndrome. There are no family members with similar phenotypes. Mutations to the COL4A1 and COL4A2 genes result in disruption of collagen found in most basement membranes, resulting in a variety of phenotypes that can make diagnosis difficult. Genetic identification of these patients is critical as these patients require a multidisciplinary approach to care and specific counselling on risk reduction techniques.
Topics: Infant; Humans; Male; Porencephaly; Collagen Type IV; Mutation; Basement Membrane; Phenotype; Family
PubMed: 38355202
DOI: 10.1136/bcr-2023-259103 -
Neurology. Genetics Apr 2021We describe a third patient with brain small vessel disease 3 (BSVD3), being the first with a homozygous essential splice site variant in the gene, with a more severe...
OBJECTIVE
We describe a third patient with brain small vessel disease 3 (BSVD3), being the first with a homozygous essential splice site variant in the gene, with a more severe phenotype than the 2 children reported earlier.
METHODS
Analysis of whole exome sequencing (WES) data of the child and parents was performed. We validated the missplicing of the homozygous variant using reverse transcription PCR and Sanger sequencing of the mRNA in a lymphocyte culture.
RESULTS
The patient presented antenatally with porencephaly on ultrasound and MRI. Postnatally, he showed a severe developmental delay, refractory epilepsy, spastic quadriplegia, and a progressive hydrocephalus. WES revealed a homozygous canonical splice site variant NM_024656.3:c.625-2A>C. PCR and Sanger sequencing of the mRNA demonstrated that 2 cryptic splice sites are activated, causing a frameshift in the major transcript and in-frame deletion in a minor transcript.
CONCLUSIONS
We report a third patient with biallelic pathogenic variants in , confirming the role of this gene in autosomal recessive BSVD3.
PubMed: 33709034
DOI: 10.1212/NXG.0000000000000564