scholarly journals De Novo KCNQ2 Mutation in One Case of Epilepsy of Infancy With Migrating Focal Seizures That Evolved to Infantile Spasms

2018 ◽  
Vol 5 ◽  
pp. 2329048X1876773 ◽  
Author(s):  
Haolin Duan ◽  
Jing Peng ◽  
Miriam Kessi ◽  
Fei Yin
Keyword(s):  
Adrenocorticotropic Hormone ◽  
De Novo ◽  
Epileptic Encephalopathy ◽  
Infantile Spasms ◽  
Heterozygous Mutation ◽  
Interictal Spikes ◽  
Rare Type ◽  
Focal Seizures ◽  
First Case ◽  
New Association

Epilepsy of infancy with migrating focal seizures (EIMFS) is a rare type of early-onset epileptic encephalopathy that is characterized by refractory migratory multifocal seizures that migrate between hemispheres. Its etiology is not well known although it is postulated to occur due to channelopathy. The authors report the first case of EIMFS due to a de novo heterozygous mutation in exon 4(c.881C>T missense mutation, p.Ala294Val, NM_172107.2) in KCNQ2 gene which later evolved into infantile spasms. However, it is the second case of EIMFS with KCNQ2 mutation. He presented with multifocal migratory partial seizures which started at the age of 8 days. Electroencephalogram examination revealed multifocal interictal spikes that migrated from one hemisphere to the other within a seizure. It was intractable with antiepileptic drugs and adrenocorticotropic hormone. He later developed spasms from the age of 8 months. Consequently, our case supports the new association between EIMFS and KCNQ2 mutations. Moreover, it enriches the disease phenotype because of transformation.

scholarly journals An Unusual Case of Infantile Spasms Due to a Pathogenic Variant in the MECP2 Gene

2019 ◽  
Vol 18 (01) ◽  
pp. 039-044
Author(s):  
Behshad Charkhand ◽  
Natarie Liu ◽  
Karlene T. Barrett ◽  
Walla Al-Hertani ◽  
Morris H. Scantlebury
Keyword(s):  
Unusual Case ◽  
De Novo ◽  
Epileptic Encephalopathy ◽  
Infantile Spasms ◽  
Mecp2 Gene ◽  
Disease Etiology ◽  
Epileptic Spasms ◽  
Uncertain Significance ◽  
Atypical Presentations ◽  
De Novo Variant

AbstractThe infantile spasms (IS) syndrome is a developmental epileptic encephalopathy disorder characterized by epileptic spasms occurring in infancy, hypsarrhythmia on the electroencephalography (EEG) and developmental arrest or regression. The etiologies include structural, metabolic, and genetic causes. We report an unusual case of IS due to a de novo variant in the MECP2 gene. The patient also had variants of uncertain significance in the SCN9A and SCN5A genes inherited from the father and mother, respectively. This report highlights the need for broad genetic testing in MECP2-related disorders with atypical presentations to better understand the disease etiology.

scholarly journals A patient with lissencephaly, developmental delay, and infantile spasms, due to de novo heterozygous mutation of KIF 2A

2016 ◽  
Vol 4 (6) ◽  
pp. 599-603 ◽  
Author(s):  
Guoling Tian ◽  
Ana G. Cristancho ◽  
Holly A. Dubbs ◽  
Grant T. Liu ◽  
Nicholas J. Cowan ◽  
...  
Keyword(s):  
Developmental Delay ◽  
De Novo ◽  
Infantile Spasms ◽  
Heterozygous Mutation

scholarly journals Case Report: Causative De novo Variants of KCNT2 for Developmental and Epileptic Encephalopathy

2021 ◽  
Vol 12 ◽  
Author(s):  
Pan Gong ◽  
Xianru Jiao ◽  
Dan Yu ◽  
Zhixian Yang
Keyword(s):  
De Novo ◽  
Gene Mutations ◽  
Epileptic Encephalopathy ◽  
Infantile Spasms ◽  
Loss Of Function ◽  
Gain Of Function ◽  
Dysmorphic Features ◽  
Pathogenic Variants ◽  
Ohtahara Syndrome ◽  
Whole Exome

Objective:KCNT2 gene mutations had been described to cause developmental and epileptic encephalopathies (DEEs). In this study, we presented the detailed clinical features and genetic analysis of two unrelated patients carrying two de novo variants in KCNT2 and reviewed eight different cases available in publications.Methods: Likely pathogenic variants were identified by whole exome sequencing; clinical data of the patients were retrospectively collected and analyzed.Results: Our two unrelated patients were diagnosed with Ohtahara syndrome followed by infantile spasms (IS) and possibly the epilepsy of infancy with migrating focal seizures (EIMFS), respectively. They both manifested dysmorphic features with hirsute arms, thick hair, prominent eyebrows, long and thick eyelashes, a broad nasal tip, and short and smooth philtrum. In the eight patients reported previously, two was diagnosed with IS carrying a ‘change-of-function' mutation and a gain-of-function mutation, respectively, two with EIMFS-like carrying a gain-of-function mutation and a loss-of-function mutation, respectively, one with EIMFS carrying a loss-of-function mutation, three with DEE without functional analysis. Among them, two patients with gain-of-function mutations both exhibited dysmorphic features and presented epilepsy phenotype, which was similar to our patients.Conclusion: Overall, the most common phenotypes associated with KCNT2 mutation were IS and EIMFS. Epilepsy phenotype associated with gain- and loss-of-function mutations could overlap. Additional KCNT2 cases will help to make genotype-phenotype correlations clearer.

scholarly journals Early surgical intervention for structural infantile spasms in two patients under 6 months old: a case report

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Haiyan Yang ◽  
Zhiquan Yang ◽  
Jing Peng ◽  
Yehong Huang ◽  
Zhuanyi Yang ◽  
...  
Keyword(s):  
Motor Development ◽  
Surgical Intervention ◽  
Focal Cortical Dysplasia ◽  
Brain Magnetic Resonance Imaging ◽  
Epileptic Encephalopathy ◽  
Infantile Spasms ◽  
Focal Seizures ◽  
Developmental Retardation ◽  
Case Presentations

Abstract Background Infantile spasms (IS) are the most common childhood epileptic encephalopathy. Focal cortical dysplasia (FCD) and gray matter heterotopias (GH) are common structural causes of IS. The recommended first-line treatment for IS patients with structural causes is surgical intervention, according to the International League Against Epilepsy (ILAE) commission guidelines. However, there is currently no consensus on appropriate timings of surgery. Case presentations Two structural IS cases are presented here: one was caused by FCD, and the other by GH. Both patients exhibited recurrent seizures at the age of 2 months, had poor responses to various antiepileptic drugs (AEDs) and displayed severe mental and motor developmental retardation. Seizure types included focal seizures and spasms. Brain magnetic resonance imaging showed abnormal gray signal or suspicious FCD lesions that coincided with the origin of the focal seizures. The patients underwent lesion resection before the age of 6 months. Follow-up observation showed that seizures of both patients were completely controlled several days after the surgery. All AEDs were gradually reduced in dosage within 1 year, and the mental and motor development almost returned to normal. Conclusion Early resection of lesions in structural IS patients has benefits of effectively controlling convulsions and improving developmental retardation. Infants at several months of age can well tolerate craniotomy, and their cognitive development is more likely to return to normal after early surgery.

A De novo Loss-of-Function Mutation in PAFAH1B1 Identified in a Single Case with Agyria–Pachygyria Complex

2019 ◽  
Vol 18 (01) ◽  
pp. 033-038
Author(s):  
Yali Ou ◽  
Bingwu Xiang ◽  
Liu Yang ◽  
Wei Chen ◽  
Xiang Chen ◽  
...  
Keyword(s):  
De Novo ◽  
Single Case ◽  
Bioinformatic Analysis ◽  
Heterozygous Mutation ◽  
Loss Of Function ◽  
Speech Impairment ◽  
Affected Child ◽  
Neuropsychological Disorders ◽  
First Case ◽  
Whole Exome

AbstractTo identify genetic causes in affected infants with abnormalities of brain development, including malformations of cortical development–associated neuropsychological disorders, affected infants were recruited based on their clinical examination and cranial imaging studies. Trio whole-exome sequencing (WES), bioinformatic analysis, and genotype–phenotype correlations were performed for 20 affected subjects to identify candidate mutations, followed by Sanger sequencing for further verification. In the present study, we identified a de novo heterozygous mutation (c.265C > T, p.R89*) of the PAFAH1B1 gene in the affected child with epilepsy, speech impairment, and cerebral palsy. The mutation was predicted to be a null loss-of-function allele, which was not found in ExAC and the Chinse Han Exome Sequences databases. Magnetic resonance imaging of the brain demonstrated bilateral parieto-occipital and temporal lissencephaly as well as frontal partial pachygyria in the affected child. This is the first case with agyria–pachygyria complex due to a nonsense mutation in the Chinese population identified by a trio WES approach.

A de novo heterozygous mutation in KCNC2 gene implicated in severe developmental and epileptic encephalopathy

2020 ◽  
Vol 63 (4) ◽  
pp. 103848 ◽  
Author(s):  
Luigi Vetri ◽  
Francesco Calì ◽  
Mirella Vinci ◽  
Carmelo Amato ◽  
Michele Roccella ◽  
...  
Keyword(s):  
De Novo ◽  
Epileptic Encephalopathy ◽  
Heterozygous Mutation

Treatment of Infantile Spasms

2011 ◽  
Vol 26 (11) ◽  
pp. 1411-1421 ◽  
Author(s):  
Carl E. Stafstrom ◽  
Barry G. W. Arnason ◽  
Tallie Z. Baram ◽  
Anna Catania ◽  
Miguel A. Cortez ◽  
...  
Keyword(s):  
New York ◽  
Adrenocorticotropic Hormone ◽  
Clinical Care ◽  
Treatment Options ◽  
Epileptic Encephalopathy ◽  
Experimental Models ◽  
Infantile Spasms ◽  
Therapeutic Effects ◽  
Experimental Approaches ◽  
Research Questions

Infantile spasms is an epileptic encephalopathy of early infancy with specific clinical and electroencephalographic (EEG) features, limited treatment options, and a poor prognosis. Efforts to develop improved treatment options have been hindered by the lack of experimental models in which to test prospective therapies. The neuropeptide adrenocorticotropic hormone (ACTH) is effective in many cases of infantile spasms, although its mechanism(s) of action is unknown. This review describes the emerging candidate mechanisms that can underlie the therapeutic effects of ACTH in infantile spasms. These mechanisms can ultimately help to improve understanding and treatment of the disease. An overview of current treatments of infantile spasms, novel conceptual and experimental approaches to infantile spasms treatment, and a perspective on remaining clinical challenges and current research questions are presented here. This summary derives from a meeting of specialists in infantile spasms clinical care and research held in New York City on June 14, 2010.

scholarly journals Prenatal diagnosis of feta noncompaction cardiomyopathy with de novo CALM2 mutation

2021 ◽  
Author(s):  
wen zhang ◽  
xiaohui dai ◽  
Hanmin Liu ◽  
Lei Li ◽  
Shu Zhou ◽  
...  
Keyword(s):  
Case Report ◽  
Prenatal Diagnosis ◽  
Exome Sequencing ◽  
Genomic Dna ◽  
De Novo ◽  
Heterozygous Mutation ◽  
Histopathologic Examination ◽  
Noncompaction Cardiomyopathy ◽  
First Case ◽  
Whole Exome

We report what apprears to be the first case of fetal noncompaction cardiomyopathy in both ventricles accompanied by a mutation in the calmodulin gene (CALM2): A 25-year-old woman was referred to our hospital at 25+1 weeks of gestation for evaluation of fetal defects. A postnatal echocardiography showed biventricular noncompaction cardiomyopathy. After terminated the pregnancy, fetal noncompaction cardiomyopathy was comfirmed by autopsy and histopathologic examination. And the whole-exome sequencing of genomic DNA demonstrated a de novo heterozygous mutation (c.389A>G;p.D130G) in CALM2, whereas the parents were normal. In this case report, we highlight the gene mutation in noncompaction cardiomyopathy.

scholarly journals A de novo SCN8A heterozygous mutation in a child with epileptic encephalopathy: a case report

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Kao-Min Lin ◽  
Geng Su ◽  
Fengpeng Wang ◽  
Xiaobin Zhang ◽  
Yuanqing Wang ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Exome Sequencing ◽  
De Novo ◽  
Intractable Epilepsy ◽  
Bioinformatic Analysis ◽  
Epileptic Encephalopathy ◽  
De Novo Mutation ◽  
Heterozygous Mutation ◽  
Targeted Exome Sequencing ◽  
Complex Disorder

Abstract Background Epilepsy is a complex disorder caused by various factors, including genetic aberrance. Recent studies have identified an essential role of the sodium channel Nav1.6, encoded by the gene SCN8A, in epileptic encephalopathy. Case presentation Using parent-offspring trio targeted-exome sequencing, we identified a de novo heterozygous missense mutation c.3953A > G (p.N1318S) in SCN8A in a 3-year-and-9-month Chinese female patient with early infantile epileptic encephalopathy and a normal magnetic resonance imaging of the brain. Conclusions This de novo mutation was only detected in the patient but not in her parents. Bioinformatic analysis indicates the pathogenicity of this mutation. Administration of the sodium channel blocker well controlled seizures in the patient. Therefore, we recommend trio targeted-exome sequencing as a routine method for pathogenic variant screening in patients with intractable epilepsy and a normal MRI.

Use of Perampanel and a Ketogenic Diet in Nonketotic Hyperglycinemia: A Case Report

2020 ◽  
Vol 51 (06) ◽  
pp. 417-420
Author(s):  
Atsuro Daida ◽  
Shin-ichiro Hamano ◽  
Satoru Ikemoto ◽  
Yuko Hirata ◽  
Ryuki Matsuura ◽  
...  
Keyword(s):  
Ketogenic Diet ◽  
Adrenocorticotropic Hormone ◽  
Seizure Control ◽  
Epileptic Encephalopathy ◽  
Severe Form ◽  
Focal Seizures ◽  
Aspartate Receptor ◽  
Epileptic Spasms ◽  
Glycine Cleavage ◽  
Nonketotic Hyperglycinemia

Abstract Background Nonketotic hyperglycinemia is a severe form of early onset epileptic encephalopathy caused by disturbances in the glycine cleavage system; the neurological damage is mainly attributed to overstimulation of the N-methyl-D-aspartate receptor. Case The patient presented with a severe form of nonketotic hyperglycinemia and experienced frequent epileptic spasms and focal seizures, which were resistant to vigabatrin, adrenocorticotropic hormone therapy, and combined dextromethorphan and sodium benzoate treatments. By 9 months of age, perampanel reduced epileptic spasms by >50%. At 14 months of age, the ketogenic diet markedly reduced focal seizures and glycine levels in the cerebrospinal fluid. Conclusion Perampanel reduced fast excitatory neuronal activity, which was induced by an α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor, followed by prolonged electrical depolarizations due to an N-methyl-D-aspartate receptor. Furthermore, the ketogenic diet may have modulated the excessive neurotoxic cascade through the N-methyl-D-aspartate receptor. Perampanel and ketogenic diet were effective for seizure control in our patient.

Sign in / Sign up

Export Citation Format

Share Document