A novel pathogenic variant in DOCK 7 gene in an infant with dysmorphism, epileptic encephalopathy and cortical blindness

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Dipti Kapoor ◽  
Aakanksha Anand ◽  
Shahyan Siddiqui ◽  
Suvasini Sharma
Keyword(s):  
Epileptic Encephalopathy ◽  
Cortical Blindness ◽  
Pathogenic Variant

Beneficial effects of the ketogenic diet on drug-resistant epileptic encephalopathy associated with a de novo NBEA pathogenic variant

2021 ◽  
Vol 23 (5) ◽  
pp. 739-743
Author(s):  
Silvia Schiavoni ◽  
Carlotta Spagnoli ◽  
Susanna Rizzi ◽  
Grazia Gabriella Salerno ◽  
Daniele Frattini ◽  
...  
Keyword(s):  
Ketogenic Diet ◽  
De Novo ◽  
Epileptic Encephalopathy ◽  
Pathogenic Variant ◽  
Drug Resistant ◽  
Beneficial Effects

scholarly journals Boricua Founder Variant in FRRS1L Causes Epileptic Encephalopathy With Hyperkinetic Movements

2020 ◽  
Vol 36 (2) ◽  
pp. 93-98
Author(s):  
Imane Abdelmoumen ◽  
Sandra Jimenez ◽  
Ignacio Valencia ◽  
Joseph Melvin ◽  
Agustin Legido ◽  
...  
Keyword(s):  
Movement Disorder ◽  
Puerto Rican ◽  
Cerebellar Atrophy ◽  
Intractable Epilepsy ◽  
Brain Magnetic Resonance Imaging ◽  
Epileptic Encephalopathy ◽  
Pathogenic Variant ◽  
Global Developmental Delay ◽  
Neurodevelopmental Outcomes ◽  
Developmental Regression

Objective: To describe a founder mutation effect and the clinical phenotype of homozygous FRRS1L c.737_739delGAG (p.Gly246del) variant in 15 children of Puerto Rican (Boricua) ancestry presenting with early infantile epileptic encephalopathy (EIEE-37) with prominent movement disorder. Background: EIEE-37 is caused by biallelic loss of function variants in the FRRS1L gene, which is critical for AMPA-receptor function, resulting in intractable epilepsy and dyskinesia. Methods: A retrospective, multicenter chart review of patients sharing the same homozygous FRRS1L (p.Gly246del) pathogenic variant identified by clinical genetic testing. Clinical information was collected regarding neurodevelopmental outcomes, neuroimaging, electrographic features and clinical response to antiseizure medications. Results: Fifteen patients from 12 different families of Puerto Rican ancestry were homozygous for the FRRS1L (p.Gly246del) pathogenic variant, with ages ranging from 1 to 25 years. The onset of seizures was from 6 to 24 months. All had hypotonia, severe global developmental delay, and most had hyperkinetic involuntary movements. Developmental regression during the first year of life was common (86%). Electroencephalogram showed hypsarrhythmia in 66% (10/15), with many older children evolving into Lennox-Gastaut syndrome. Six patients demonstrated progressive volume loss and/or cerebellar atrophy on brain magnetic resonance imaging (MRI). Conclusions: We describe the largest cohort to date of patients with epileptic encephalopathy. We estimate that 0.76% of unaffected individuals of Puerto Rican ancestry carry this pathogenic variant due to a founder effect. Children homozygous for the FRRS1L (p.Gly246del) Boricua variant exhibit a very homogenous phenotype of early developmental regression and epilepsy, starting with infantile spasms and evolving into Lennox-Gastaut syndrome with hyperkinetic movement disorder.

scholarly journals Characteristic facial features and cortical blindness distinguish the DOCK7 ‐related epileptic encephalopathy

2021 ◽  
Author(s):  
Edda Haberlandt ◽  
Taras Valovka ◽  
Tanja Janjic ◽  
Thomas Müller ◽  
Georgios Blatsios ◽  
...  
Keyword(s):  
Epileptic Encephalopathy ◽  
Cortical Blindness ◽  
Facial Features

scholarly journals Mutations in DOCK7 in Individuals with Epileptic Encephalopathy and Cortical Blindness

2014 ◽  
Vol 94 (6) ◽  
pp. 891-897 ◽  
Author(s):  
Isabelle Perrault ◽  
Fadi F. Hamdan ◽  
Marlène Rio ◽  
José-Mario Capo-Chichi ◽  
Nathalie Boddaert ◽  
...  
Keyword(s):  
Epileptic Encephalopathy ◽  
Cortical Blindness

ISDN2014_0400: Mutations in DOCK7 in individuals with epileptic encephalopathy and cortical blindness

2015 ◽  
Vol 47 (Part_A) ◽  
pp. 119-120
Author(s):  
Fadi F. Hamdan ◽  
Isabelle Perrault ◽  
Marlène Rio ◽  
José‐Mario Capo‐Chichi ◽  
Nathalie Boddaert ◽  
...  
Keyword(s):  
Epileptic Encephalopathy ◽  
Cortical Blindness

scholarly journals Case Report: Clinical Features of a Chinese Boy With Epileptic Seizures and Intellectual Disabilities Who Carries a Truncated NUS1 Variant

2021 ◽  
Vol 9 ◽  
Author(s):  
Pingli Zhang ◽  
Di Cui ◽  
Peiyuan Liao ◽  
Xiang Yuan ◽  
Nuan Yang ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Clinical Features ◽  
De Novo ◽  
Epileptic Seizures ◽  
Epileptic Encephalopathy ◽  
Chinese Patient ◽  
Pathogenic Variant ◽  
Phenotype Correlation ◽  
Congenital Disorder Of Glycosylation ◽  
Pathogenic Variants

The mental retardation-55 with seizures (MRD55) is a rare genetic disease characterized by developmental delay, intellectual disability, language delay and multiple types of epileptic seizures. It is caused by pathogenic variants of the NUS1 gene, which encodes Nogo-B receptor (NgBR), a necessary subunit for the glycosylation reactions in mammals. To date, 25 disease-causing mutations of NUS1 have been reported, which are responsible for various diseases, including dystonia, Parkinson's disease, developmental and epileptic encephalopathy as well as congenital disorder of glycosylation. In addition, only 9 of these mutations were reported with detailed clinical features. There are no reports about Chinese cases with MRD55. In this study, a novel, de novo pathogenic variant of NUS1 (c.51_54delTCTG, p.L18Tfs*31) was identified in a Chinese patient with intellectual disability and epileptic seizures. This pathogenic variant resulted in truncated NgBR proteins, which might be the cause of the clinical features of the patient. Oxcarbazepine was an effective treatment for improving speech and movement of the patient, who consequently presented with no seizure. With this novel pathogenic variant found in NUS1, we expand the genotype spectrum of MRD55 and provide valuable insights into the potential genotype-phenotype correlation.

scholarly journals The phenotype of SCN8A developmental and epileptic encephalopathy

Neurology ◽  
2018 ◽  
Vol 91 (12) ◽  
pp. e1112-e1124 ◽  
Author(s):  
Elena Gardella ◽  
Carla Marini ◽  
Marina Trivisano ◽  
Mark P. Fitzgerald ◽  
Michael Alber ◽  
...  
Keyword(s):  
Early Childhood ◽  
Brain Mri ◽  
Gastrointestinal Symptoms ◽  
Brain Dysfunction ◽  
Clonic Seizure ◽  
Epileptic Encephalopathy ◽  
Cortical Blindness ◽  
Beta Activity ◽  
Risk Of Death ◽  
Extrapyramidal Signs

ObjectiveTo delineate the electroclinical features of SCN8A infantile developmental and epileptic encephalopathy (EIEE13, OMIM #614558).MethodsTwenty-two patients, aged 19 months to 22 years, underwent electroclinical assessment.ResultsSixteen of 22 patients had mildly delayed development since birth. Drug-resistant epilepsy started at a median age of 4 months, followed by developmental slowing, pyramidal/extrapyramidal signs (22/22), movement disorders (12/22), cortical blindness (17/22), sialorrhea, and severe gastrointestinal symptoms (15/22), worsening during early childhood and plateauing at age 5 to 9 years. Death occurred in 4 children, following extreme neurologic deterioration, at 22 months to 5.5 years. Nonconvulsive status epilepticus recurred in 14 of 22 patients. The most effective antiepileptic drugs were oxcarbazepine, carbamazepine, phenytoin, and benzodiazepines. EEG showed background deterioration, epileptiform abnormalities with a temporo-occipital predominance, and posterior delta/beta activity correlating with visual impairment. Video-EEG documented focal seizures (FS) (22/22), spasm-like episodes (8/22), cortical myoclonus (8/22), and myoclonic absences (1/22). FS typically clustered and were prolonged (<20 minutes) with (1) cyanosis, hypomotor, and vegetative semiology, sometimes unnoticed, followed by (2) tonic-vibratory and (3) (hemi)-clonic manifestations ± evolution to a bilateral tonic-clonic seizure. FS had posterior-temporal/occipital onset, slowly spreading and sometimes migrating between hemispheres. Brain MRI showed progressive parenchymal atrophy and restriction of the optic radiations.Conclusions:SCN8A developmental and epileptic encephalopathy has strikingly consistent electroclinical features, suggesting a global progressive brain dysfunction primarily affecting the temporo-occipital regions. Both uncontrolled epilepsy and developmental compromise contribute to the profound impairment (increasing risk of death) during early childhood, but stabilization occurs in late childhood.

SCN2A and Its Related Epileptic Phenotypes

2021 ◽  
Author(s):  
Andrea D. Praticò ◽  
Alessandro Giallongo ◽  
Marta Arrabito ◽  
Silvia D'Amico ◽  
Maria Cristina Gauci ◽  
...  
Keyword(s):  
De Novo ◽  
Wide Spectrum ◽  
Epileptic Encephalopathy ◽  
Pathogenic Variant ◽  
Channel Blockers ◽  
Epileptic Encephalopathies ◽  
Ohtahara Syndrome ◽  
Affected Parent ◽  
Environmental Causes ◽  
Almost All

AbstractEpilepsies due to SCN2A mutations can present with a broad range of phenotypes that are still not fully understood. Clinical characteristics of SNC2A-related epilepsy may vary from neonatal benign epilepsy to early-onset epileptic encephalopathy, including Ohtahara syndrome and West syndrome, and epileptic encephalopathies occurring at later ages (usually within the first 10 years of life). Some patient may present with intellectual disability and/or autism or movement disorders and without epilepsy. The heterogeneity of the phenotypes associated to such genetic mutations does not always allow the clinician to address his suspect on this gene. For this reason, diagnosis is usually made after a multiple gene panel examination through next generation sequencing (NGS) or after whole exome sequencing (WES) or whole genome sequencing (WGS). Subsequently, confirmation by Sanger sequencing can be obtained. Mutations in SCN2A are inherited as an autosomal dominant trait. Most individuals diagnosed with SCN2A–benign familial neonatal-infantile seizures (BFNIS) have an affected parent; however, hypothetically, a child may present SCN2A-BNFNIS as the result of a de novo pathogenic variant. Almost all individuals with SCN2A and severe epileptic encephalopathies have a de novo pathogenic variant. SNC2A-related epilepsies have not shown a clear genotype–phenotype correlation; in some cases, a same variant may lead to different presentations even within the same family and this could be due to other genetic factors or to environmental causes. There is no “standardized” treatment for SCN2A-related epilepsy, as it varies in relation to the clinical presentation and the phenotype of the patient, according to its own gene mutation. Treatment is based mainly on antiepileptic drugs, which include classic wide-spectrum drugs, such as valproic acid, levetiracetam, and lamotrigine. However, specific agents, which act directly modulating the sodium channels activity (phenytoin, carbamazepine, oxcarbamazepine, lamotrigine, and zonisamide), have shown positive result, as other sodium channel blockers (lidocaine and mexiletine) or even other drugs with different targets (phenobarbital).

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