Lafora body disease: a case of progressive myoclonic epilepsy

Progressive myoclonic epilepsy (PME) is a progressive neurological disorder. Unfortunately, until now, no definitive curative treatment exists; however, it is of utmost importance to identify patients with PME. The underlying aetiology can be pinpointed if methodological clinical evaluation is performed, followed by subsequent genetic testing. We report a case of PME that was diagnosed as Lafora body disease. This case emphasises that, suspecting and identifying PME is important so as to start appropriate treatment and reduce the probability of morbidity and prognosticate the family.

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Progressive Myoclonic Epilepsy: Review Article with A Case Report of Lafora Disease

Bangladesh Journal of Child Health ◽

10.3329/bjch.v42i3.39269 ◽

2018 ◽

Vol 42 (3) ◽

pp. 138-147

Author(s):

Selina Husna Banu ◽

Mashaya Zaman Koli

Keyword(s):

Autosomal Recessive ◽

Early Stage ◽

Clinical History ◽

Genetic Mutation ◽

Myoclonic Epilepsy ◽

Epilepsy Syndrome ◽

Lafora Disease ◽

Clinical Criteria ◽

Lafora Body ◽

Progressive Myoclonic Epilepsy

Progressive myoclonic epilepsy (PME) is an autosomal recessive, apparently a rare complex epilepsy syndrome. Among different types of PME, lafora body disease is more quickly progressive usually fatal within 2nd and 3rd decade. They are characterized by childhood or adolescent onset difficult to control multiple type seizures including myoclonous, generalized tonic clonic, absences, psychomotor regression with ataxia, dementia, dysarthria, visual hallucinations, and other general features. Early suspicion is important that leads to the rational diagnostic workout. The electro-clinical criteria would help a lot to exclude the benign epilepsy syndrome such as juvenile myoclonic epilepsy (JME) and suspect PME at the early stage of the complex epilepsy syndrome. Diagnosis is further clarified and confirmed by finding lafora body in skin and genetic study. Genetic mutation found in more than 87% cases in EPM2A gene or the EPM2B also known as NHLRC1 gene and are inherited in an autosomal recessive manner. EMP2A gene is located on chromosome 6q24. They are reported from Mediterranean basin, central Asia, India, Pakistan, northern Africa and Middle East where consanguineous marriage is common. We report a diagnosed case for the first time in Bangladesh. With the detail clinical history, rational use of the available investigation tools and clinical suspicion, diagnosis of the disorder at its early stage is possible. The rapid progress in genetic therapy would be a great hope in near future. Bangladesh J Child Health 2018; VOL 42 (3) :138-147

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Role of levetiracetam in refractory seizures due to a rare progressive myoclonic epilepsy: Lafora body disease

BMJ Case Reports ◽

10.1136/bcr.01.2010.2653 ◽

2010 ◽

Vol 2010 (nov04 1) ◽

pp. bcr0120102653-bcr0120102653 ◽

Cited By ~ 2

Author(s):

M. Hashmi ◽

F. Saleem ◽

M. S. Mustafa ◽

M. Sheerani ◽

Z. Ehtesham ◽

...

Keyword(s):

Myoclonic Epilepsy ◽

Lafora Body ◽

Progressive Myoclonic Epilepsy ◽

Refractory Seizures

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Novel SCN5A p.Val1667Asp Missense Variant Segregation and Characterization in a Family with Severe Brugada Syndrome and Multiple Sudden Deaths

International Journal of Molecular Sciences ◽

10.3390/ijms22094700 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4700

Author(s):

Michelle M. Monasky ◽

Emanuele Micaglio ◽

Giuseppe Ciconte ◽

Ilaria Rivolta ◽

Valeria Borrelli ◽

...

Keyword(s):

Genetic Testing ◽

Family History ◽

Risk Stratification ◽

Brugada Syndrome ◽

Electrophysiological Study ◽

Functional Characterization ◽

The Family ◽

Novel Variant ◽

History Of ◽

Scn5a Gene

Genetic testing in Brugada syndrome (BrS) is still not considered to be useful for clinical management of patients in the majority of cases, due to the current lack of understanding about the effect of specific variants. Additionally, family history of sudden death is generally not considered useful for arrhythmic risk stratification. We sought to demonstrate the usefulness of genetic testing and family history in diagnosis and risk stratification. The family history was collected for a proband who presented with a personal history of aborted cardiac arrest and in whom a novel variant in the SCN5A gene was found. Living family members underwent ajmaline testing, electrophysiological study, and genetic testing to determine genotype-phenotype segregation, if any. Patch-clamp experiments on transfected human embryonic kidney 293 cells enabled the functional characterization of the SCN5A novel variant in vitro. In this study, we provide crucial human data on the novel heterozygous variant NM_198056.2:c.5000T>A (p.Val1667Asp) in the SCN5A gene, and demonstrate its segregation with a severe form of BrS and multiple sudden deaths. Functional data revealed a loss of function of the protein affected by the variant. These results provide the first disease association with this variant and demonstrate the usefulness of genetic testing for diagnosis and risk stratification in certain patients. This study also demonstrates the usefulness of collecting the family history, which can assist in understanding the severity of the disease in certain situations and confirm the importance of the functional studies to distinguish between pathogenic mutations and harmless genetic variants.

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A Comprehensive Analysis of Hungarian MODY Patients—Part I: Gene Panel Sequencing Reveals Pathogenic Mutations in HNF1A, HNF1B, HNF4A, ABCC8 and INS Genes

Life ◽

10.3390/life11080755 ◽

2021 ◽

Vol 11 (8) ◽

pp. 755

Author(s):

Zsolt Gaál ◽

Zsuzsanna Szűcs ◽

Irén Kántor ◽

Andrea Luczay ◽

Péter Tóth-Heyn ◽

...

Keyword(s):

Genetic Testing ◽

Low Dose ◽

Comprehensive Analysis ◽

First Line ◽

Pathogenic Mutations ◽

Appropriate Treatment ◽

Causal Genes ◽

Hnf1a Gene ◽

Gene Panel Sequencing ◽

Generation Sequencing

Maturity-onset diabetes of the young (MODY) has about a dozen known causal genes to date, the most common ones being HNF1A, HNF4A, HNF1B and GCK. The phenotype of this clinically and genetically heterogeneous form of diabetes depends on the gene in which the patient has the mutation. We have tested 450 Hungarian index patients with suspected MODY diagnosis with Sanger sequencing and next-generation sequencing and found a roughly 30% positivity rate. More than 70% of disease-causing mutations were found in the GCK gene, about 20% in the HNF1A gene and less than 10% in other MODY-causing genes. We found 8 pathogenic and 9 likely pathogenic mutations in the HNF1A gene in a total of 48 patients and family members. In the case of HNF1A-MODY, the recommended first-line treatment is low dose sulfonylurea but according to our data, the majority of our patients had been on unnecessary insulin therapy at the time of requesting their genetic testing. Our data highlights the importance of genetic testing in the diagnosis of MODY and the establishment of the MODY subtype in order to choose the most appropriate treatment.

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