scholarly journals Clinical features and outcome of 6 new patients carrying de novo KCNB1 gene mutations

2017 ◽  
Vol 3 (6) ◽  
pp. e206 ◽  
Author(s):  
Carla Marini ◽  
Michele Romoli ◽  
Elena Parrini ◽  
Cinzia Costa ◽  
Davide Mei ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
De Novo ◽  
Focal Epilepsy ◽  
Brain Mri ◽  
Somatic Mosaicism ◽  
Epileptic Encephalopathy ◽  
Seizure Onset ◽  
Severe Intellectual Disability ◽  
The Mean

Objective:To describe electroclinical features and outcome of 6 patients harboring KCNB1 mutations.Methods:Clinical, EEG, neuropsychological, and brain MRI data analysis. Targeted next-generation sequencing of a 95 epilepsy gene panel.Results:The mean age at seizure onset was 11 months. The mean follow-up of 11.3 years documented that 4 patients following an infantile phase of frequent seizures became seizure free; the mean age at seizure offset was 4.25 years. Epilepsy phenotypes comprised West syndrome in 2 patients, infantile-onset unspecified generalized epilepsy, myoclonic and photosensitive eyelid myoclonia epilepsy resembling Jeavons syndrome, Lennox-Gastaut syndrome, and focal epilepsy with prolonged occipital or clonic seizures in each and every one. Five patients had developmental delay prior to seizure onset evolving into severe intellectual disability with absent speech and autistic traits in one and stereotypic hand movements with impulse control disorder in another. The patient with Jeavons syndrome evolved into moderate intellectual disability. Mutations were de novo, 4 missense and 2 nonsense, 5 were novel, and 1 resulted from somatic mosaicism.Conclusions:KCNB1-related manifestations include a spectrum of infantile-onset generalized or focal seizures whose combination leads to early infantile epileptic encephalopathy including West, Lennox-Gastaut, and Jeavons syndromes. Long-term follow-up highlights that following a stormy phase, seizures subside or cease and treatment may be eased or withdrawn. Cognitive and motor functions are almost always delayed prior to seizure onset and evolve into severe, persistent impairment. Thus, KCNB1 mutations are associated with diffuse brain dysfunction combining seizures, motor, and cognitive impairment.

Safety and Long-term Seizure-Free Outcomes of Subdural Grid Placement in Patients With a History of Prior Craniotomy

Neurosurgery ◽  
2013 ◽  
Vol 73 (3) ◽  
pp. 395-400 ◽  
Author(s):  
Sumeet Vadera ◽  
Lara Jehi ◽  
Jorge Gonzalez-Martinez ◽  
William Bingaman
Keyword(s):  
Focal Epilepsy ◽  
Seizure Onset ◽  
Initial Surgery ◽  
Increased Risk ◽  
Initial Procedure ◽  
History Of ◽  
The Mean ◽  
Drug Resistant Epilepsy

Abstract BACKGROUND: Patients who continue or begin to have seizures after brain surgery pose significant challenges and often require an invasive electroencephalographic evaluation before reoperation for drug-resistant epilepsy. The safety and seizure-free outcomes associated with subdural grid (SDG) implantation in patients with a prior craniotomy are important for both surgeon and patient to understand before pursuing further surgery. OBJECTIVE: To evaluate the safety of SDG placement and subsequent resective surgery in patients with prior craniotomy and to characterize the seizure outcomes and their predictors after resective epilepsy surgery in this unique cohort. METHODS: We retrospectively reviewed all intractable focal epilepsy patients with a history of craniotomy who underwent SDG insertion between 2000 and 2012 at our institution. A minimum follow-up of 6 months was required. End points analyzed included complications related to each surgery and Engel classification at the last follow-up. RESULTS: The mean age of seizure onset was 15.9 years, and the mean age for the initial surgery was 24.2 years. Only 3 patients began having seizures after the initial surgery. Seven patients (7%) had a complication associated with the SDG placement, and 15 (14%) had a complication after subsequent resection, which was equivalent to the initial procedure. Forty-eight patients (44%) were in Engel class I at the last follow-up. Freedom from seizures was predicted by ictal onset at the edge of the original surgical bed, particularly in patients with lesional epilepsy. CONCLUSION: Surgical intervention with SDG monitoring does not appear to be associated with increased risk of complications in epilepsy patients with a history of prior craniotomy, and rates of freedom from seizures in this challenging group are favorable.

scholarly journals A New Case of de novo Variant c.892C>T (p.Arg298Trp) in NACC1: A First Case Report From China

2021 ◽  
Vol 9 ◽  
Author(s):  
Baiyu Lyu ◽  
Yan Dong ◽  
Juan Kang
Keyword(s):  
Intellectual Disability ◽  
Congenital Cataract ◽  
De Novo ◽  
Neurodevelopmental Disorder ◽  
Brain Mri ◽  
Case Presentation ◽  
Feeding Difficulties ◽  
Severe Intellectual Disability ◽  
First Case ◽  
Infantile Epilepsy

Background: The nucleus accumbens associated 1 (NACC1) gene is a transcription factor member of the BTB/POZ family. A de novo heterozygous c.892C>T (p.Arg298Trp) variant in the NACC1 may define a syndrome characterized by intellectual disability, infantile epilepsy, congenital cataract, and feeding difficulties.Case Presentation: We report a new case with a neurodevelopmental disorder characterized by severe intellectual disability, infantile epilepsy, congenital cataract, and feeding difficulties. Brain MRI reveals brain dysplasia. We observe a de novo heterozygous c.892C>T (p.Arg298Trp) variant in the NACC1 gene in this case. Now, the child regularly goes to the hospital for rehabilitation training (once a month). Sodium Valproate (10 mg/kg/day) and Clobazam (10 mg/kg/day) are used in the treatment of epilepsy. A total of three articles were screened, and two papers were excluded. The search revealed one article related to a syndrome caused by a de novo heterozygous c.892C>T (p.Arg298Trp) variant in the NACC1; they screened the main clinical features of eight cases of a syndrome, which were summarized and analyzed.Conclusions: The NACC1 gene is a member of the BTB/POZ family of transcription factors. A de novo heterozygous c.892C>T (p.Arg298Trp) variant in the NACC1 may define a syndrome characterized by intellectual disability, infantile epilepsy, congenital cataract, and feeding difficulties. At present, there is no effective cure. In the future, we need more cases to determine the phenotype–genotype correlation of NACC1 variants. Many questions remain to be answered, and many challenges remain to be faced. Future transcriptional studies may further clarify this rare, recurrent variant, and could potentially lead to targeted therapies.

Biallelic variants in ZNF526 cause a severe neurodevelopmental disorder with microcephaly, bilateral cataract, epilepsy and simplified gyration

2021 ◽  
pp. jmedgenet-2020-107430
Author(s):  
Maria Lisa Dentici ◽  
Viola Alesi ◽  
Mathieu Quinodoz ◽  
Barbara Robens ◽  
Andrea Guerin ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Exome Sequencing ◽  
Zinc Finger Protein ◽  
Neurodevelopmental Disorder ◽  
Brain Mri ◽  
Missense Variant ◽  
Epileptic Encephalopathy ◽  
Gene Encoding ◽  
Psychomotor Delay ◽  
Severe Intellectual Disability

BackgroundNext-generation sequencing, combined with international pooling of cases, has impressively enhanced the discovery of genes responsible for Mendelian neurodevelopmental disorders, particularly in individuals affected by clinically undiagnosed diseases. To date, biallelic missense variants in ZNF526 gene, encoding a Krüppel-type zinc-finger protein, have been reported in three families with non-syndromic intellectual disability.MethodsHere, we describe five individuals from four unrelated families with an undiagnosed neurodevelopmental disorder in which we performed exome sequencing, on a combination of trio-based (4 subjects) or single probands (1 subject).ResultsWe identified five patients from four unrelated families with homozygous ZNF526 variants by whole exome sequencing. Four had variants resulting in truncation of ZNF526; they were affected by severe prenatal and postnatal microcephaly (ranging from −4 SD to −8 SD), profound psychomotor delay, hypertonic–dystonic movements, epilepsy and simplified gyral pattern on MRI. All of them also displayed bilateral progressive cataracts. A fifth patient had a homozygous missense variant and a slightly less severe disorder, with postnatal microcephaly (−2 SD), progressive bilateral cataracts, severe intellectual disability and unremarkable brain MRI.Mutant znf526 zebrafish larvae had notable malformations of the eye and central nervous system, resembling findings seen in the human holoprosencephaly spectrum.ConclusionOur findings support the role of ZNF526 biallelic variants in a complex neurodevelopmental disorder, primarily affecting brain and eyes, resulting in severe microcephaly, simplified gyral pattern, epileptic encephalopathy and bilateral cataracts.

Long-term seizure outcomes after pediatric temporal lobectomy: does brain MRI lesion matter?

2019 ◽  
Vol 24 (2) ◽  
pp. 200-208
Author(s):  
Ravindra Arya ◽  
Francesco T. Mangano ◽  
Paul S. Horn ◽  
Sabrina K. Kaul ◽  
Serena K. Kaul ◽  
...  
Keyword(s):  
Repeated Measures ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Hippocampal Sclerosis ◽  
Brain Mri ◽  
Temporal Lobectomy ◽  
Seizure Freedom ◽  
Seizure Onset

OBJECTIVEThere is emerging data that adults with temporal lobe epilepsy (TLE) without a discrete lesion on brain MRI have surgical outcomes comparable to those with hippocampal sclerosis (HS). However, pediatric TLE is different from its adult counterpart. In this study, the authors investigated if the presence of a potentially epileptogenic lesion on presurgical brain MRI influences the long-term seizure outcomes after pediatric temporal lobectomy.METHODSChildren who underwent temporal lobectomy between 2007 and 2015 and had at least 1 year of seizure outcomes data were identified. These were classified into lesional and MRI-negative groups based on whether an epilepsy-protocol brain MRI showed a lesion sufficiently specific to guide surgical decisions. These patients were also categorized into pure TLE and temporal plus epilepsies based on the neurophysiological localization of the seizure-onset zone. Seizure outcomes at each follow-up visit were incorporated into a repeated-measures generalized linear mixed model (GLMM) with MRI status as a grouping variable. Clinical variables were incorporated into GLMM as covariates.RESULTSOne hundred nine patients (44 females) were included, aged 5 to 21 years, and were classified as lesional (73%), MRI negative (27%), pure TLE (56%), and temporal plus (44%). After a mean follow-up of 3.2 years (range 1.2–8.8 years), 66% of the patients were seizure free for ≥ 1 year at last follow-up. GLMM analysis revealed that lesional patients were more likely to be seizure free over the long term compared to MRI-negative patients for the overall cohort (OR 2.58, p < 0.0001) and for temporal plus epilepsies (OR 1.85, p = 0.0052). The effect of MRI lesion was not significant for pure TLE (OR 2.64, p = 0.0635). Concordance of ictal electroencephalography (OR 3.46, p < 0.0001), magnetoencephalography (OR 4.26, p < 0.0001), and later age of seizure onset (OR 1.05, p = 0.0091) were associated with a higher likelihood of seizure freedom. The most common histological findings included cortical dysplasia types 1B and 2A, HS (40% with dual pathology), and tuberous sclerosis.CONCLUSIONSA lesion on presurgical brain MRI is an important determinant of long-term seizure freedom after pediatric temporal lobectomy. Pediatric TLE is heterogeneous regarding etiologies and organization of seizure-onset zones with many patients qualifying for temporal plus nosology. The presence of an MRI lesion determined seizure outcomes in patients with temporal plus epilepsies. However, pure TLE had comparable surgical seizure outcomes for lesional and MRI-negative groups.

Risk of hemorrhage from de novo cerebral aneurysms

2013 ◽  
Vol 118 (1) ◽  
pp. 58-62 ◽  
Author(s):  
William J. Kemp ◽  
Daniel H. Fulkerson ◽  
Troy D. Payner ◽  
Thomas J. Leipzig ◽  
Terry G. Horner ◽  
...  
Keyword(s):  
Risk Factors ◽  
De Novo ◽  
Patient Age ◽  
Patient Âgé ◽  
Long Term Follow Up ◽  
De Novo Aneurysm ◽  
The Mean ◽  
Risk Of Hemorrhage

Object A small percentage of patients will develop a completely new or de novo aneurysm after discovery of an initial aneurysm. The natural history of these lesions is unknown. The authors undertook this statistical evaluation a large cohort of patients with both ruptured and unruptured de novo aneurysms with the aim of analyzing risk factors for rupture and estimating a risk of subarachnoid hemorrhage (SAH). Methods A review of a prospectively maintained database of all aneurysm patients treated by the vascular neurosurgery service of Goodman Campbell Brain and Spine from 1976–2010 was performed. Of the 4718 patients, 611 (13%) had long-term follow-up imaging. The authors identified 27 patients (4.4%) with a total of 32 unruptured de novo aneurysms from routine surveillance imaging. They identified another 10 patients who presented with a new SAH from a de novo aneurysm after treatment of their original aneurysm. The total study group was thus 37 patients with a total of 42 de novo aneurysms. The authors then compared the 27 patients with incidentally discovered aneurysms with the 10 patients with SAH. A statistical analysis was performed, comparing the 2 groups with respect to patient and aneurysm characteristics and risk factors. Results Thirty-seven patients were identified as having true de novo aneurysms. This group had a female predominance and a high percentage of smokers. These 37 patients had a total of 42 de novo aneurysms. Ten of these 42 aneurysms hemorrhaged. De novo aneurysms in both the SAH and non-SAH group were anatomically small (< 10 mm). The estimated risk of hemorrhage over 5 years was 14.5%, higher than the expected SAH risk of small, unruptured aneurysms reported in the ISUIA (International Study of Unruptured Intracranial Aneurysms) trial. There was no statistically significant correlation between hemorrhage and any of the following risk factors: hypertension, diabetes, tobacco and alcohol use, polycystic kidney disease, or previous SAH. There was a statistically significant between-groups difference with respect to patient age, with the mean patient age being significantly older in the SAH aneurysm group than in the non-SAH group (p = 0.047). This is likely reflective of longer follow-up and discovery time, as the mean length of time between initial treatment and discovery of the de novo aneurysm was longer in the SAH group (p = 0.011). Conclusions While rare, de novo aneurysms may have a risk for SAH that is comparatively higher than the risk associated with similarly sized, small, initially discovered unruptured saccular aneurysms. The authors therefore recommend long-term follow-up for all patients with aneurysms, and they consider a more aggressive treatment strategy for de novo aneurysms than for incidentally discovered initial aneurysms.

Frequency, Predictors, and Outcome of Seizures in Patients With Myelomeningocele: Single-Center Retrospective Cohort Study

2021 ◽  
pp. 088307382110531
Author(s):  
Cemal Karakas ◽  
Emin Fidan ◽  
Kapil Arya ◽  
Troy Webber ◽  
Joan B. Cracco
Keyword(s):  
Good Prognosis ◽  
Cortical Atrophy ◽  
Seizure Freedom ◽  
Single Center ◽  
Seizure Onset ◽  
Shunt Procedure ◽  
History Of ◽  
The Mean

To determine the frequency, predictors, and outcomes of seizures in patients with myelomeningocele, we retrospectively analyzed the data from patients with myelomeningocele followed longitudinally at a single center from 1975 to 2013. We identified a total of 122 patients (61% female). The mean follow-up duration was 11.1 years (minimum-maximum = 0-34.5 years, SD = 8.8, median = 9.1 years). A total of 108 (88.5%) patients had hydrocephalus, and 98 (90.7%) of those patients required a ventriculoperitoneal shunt procedure. Twenty-four (19.7%) patients manifested with seizures, 23 of whom had hydrocephalus. The average age of seizure onset was 4.8 years (median 2 years of age). Falx dysgenesis ( P = .004), lumbar myelomeningocele ( P = .007), and cortical atrophy ( P = .028) were significantly associated with epileptic seizure development. The average seizure-free period at the last follow-up in patients with a history of myelomeningocele and seizures was 8.1 years. We conclude that myelomeningocele patients with seizures have an overall good prognosis with considerable long-term seizure freedom.

RHOBTB2 p.Arg511Trp Mutation in Early Infantile Epileptic Encephalopathy-64: Review and Case Report

2021 ◽  
Author(s):  
J Fonseca ◽  
C Melo ◽  
C Ferreira ◽  
M Sampaio ◽  
R Sousa ◽  
...  
Keyword(s):  
Case Report ◽  
Intellectual Disability ◽  
Status Epilepticus ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Epileptic Encephalopathy ◽  
Btb Domain ◽  
Pathogenic Variants ◽  
Severe Intellectual Disability ◽  
Whole Exome

AbstractEarly infantile epileptic encephalopathy-64 (EIEE 64), also called RHOBTB2-related developmental and epileptic encephalopathy (DEE), is caused by heterozygous pathogenic variants (EIEE 64; MIM#618004) in the Rho-related BTB domain-containing protein 2 (RHOBTB2) gene. To date, only 13 cases with RHOBTB2-related DEE have been reported. We add to the literature the 14th case of EIEE 64, identified by whole exome sequencing, caused by a heterozygous pathogenic variant in RHOBTB2 (c.1531C > T), p.Arg511Trp. This additional case supports the main features of RHOBTB2-related DEE: infantile-onset seizures, severe intellectual disability, impaired motor functions, postnatal microcephaly, recurrent status epilepticus, and hemiparesis after seizures.

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