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V L Sheen,
M Topçu, S Berkovic,
D Yalnizoglu,
I Blatt,
A Bodell,
R S Hill,
V S Ganesh,
T J Cherry,
Y Y Shugart,
C A Walsh
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ABSTRACT: Familial periventricular heterotopia (PH) represents a disorder of neuronal migration resulting in multiple gray matter nodules along the lateral ventricular walls. Prior studies have shown that mutations in the filamin A (FLNA) gene can cause PH through an X-linked dominant inheritance pattern.
To classify cortical malformation syndromes associated with PH.
Analyses using microsatellite markers directed toward genomic regions of FLNA and to a highly homologous autosomal gene, FLNB, were performed on two pedigrees to evaluate for linkage with either filamin gene.
Two consanguineous pedigrees with PH that suggest an autosomal recessive inheritance pattern are reported. MRI of the brain revealed periventricular nodules of cerebral gray matter intensity, typical for PH. Seizures or developmental delay appeared to be a common presenting feature. Microsatellite analysis suggested no linkage to FLNA or FLNB.
Autosomal recessive PH is another syndromic migrational disorder, distinct from X-linked dominant PH. Further classification of these different syndromes will provide an approach for genetic evaluation.
Neurology 05/2003; 60(7):1108-12. · 8.31 Impact Factor
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A Bernasconi,
V Martinez,
P Rosa-Neto,
D D'Agostino,
N Bernasconi, S Berkovic,
M MacKay,
A S Harvey,
A Palmini,
J C da Costa, [......],
H I Kim,
M Connolly,
A Olivier,
F Dubeau,
E Andermann,
R Guerrini,
W Whisler,
L de Toledo-Morrell,
F Morrell,
F Andermann
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ABSTRACT: To analyze the results of surgical treatment of intractable epilepsy in patients with subcortical band heterotopia, or double cortex syndrome, a diffuse neuronal migration disorder.
We studied eight patients (five women) with double cortex syndrome and intractable epilepsy. All had a comprehensive presurgical evaluation including prolonged video-EEG recordings and magnetic resonance imaging (MRI).
All patients had partial seizures, with secondary generalization in six of them. Neurologic examination was normal in all. Three were of normal intelligence, and five were mildly retarded. Six patients underwent invasive EEG recordings, three of them with subdural grids and three with stereotactic implanted depth electrodes (SEEG). Although EEG recordings showed multilobar epileptic abnormalities in most patients, regional or focal seizure onset was recorded in all. MRI showed bilateral subcortical band heterotopia, asymmetric in thickness in three. An additional area of cortical thickening in the left frontal lobe was found in one patient. Surgical procedures included multiple subpial transections in two patients, frontal lesionectomy in one, temporal lobectomy with amygdalohippocampectomy in five, and an additional anterior callosotomy in one. Five patients had no significant improvement, two had some improvement, and one was greatly improved.
Our results do not support focal surgical removal of epileptogenic tissue in patients with double cortex syndrome, even in the presence of a relatively localized epileptogenic area.
Epilepsia 10/2001; 42(9):1124-9. · 3.96 Impact Factor
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J G Gleeson,
R F Luo,
P E Grant,
R Guerrini,
P R Huttenlocher,
M J Berg,
S Ricci,
R Cusmai,
J W Wheless, S Berkovic,
I Scheffer,
W B Dobyns,
C A Walsh
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ABSTRACT: Mutations in the X-linked doublecortin gene appear in many sporadic cases of double cortex (DC; also known as subcortical band heterotopia), a neuronal migration disorder causing epilepsy and mental retardation. The purpose of this study was to examine why a significant percentage of sporadic DC patients had been found not to harbor doublecortin mutations and to determine whether clinical features or magnetic resonance imaging scan appearance could distinguish between patients with and without doublecortin mutations. Magnetic resonance imaging scan analysis differentiated patients into the following four groups: anterior biased/global DC with doublecortin mutation (16 of 30; 53%), anterior biased/global DC without mutation (8 of 30; 27%), posterior biased DC without mutation (3 of 30; 10%), and limited/unilateral DC without mutation (3 of 30; 10%). The presence of these atypical phenotypes suggests that other genetic loci or mosaicism at the doublecortin locus may be responsible for this diversity of DC cases.
Annals of Neurology 03/2000; 47(2):265-9. · 11.09 Impact Factor
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J G Gleeson,
S R Minnerath,
J W Fox,
K M Allen,
R F Luo,
S E Hong,
M J Berg,
R Kuzniecky,
P J Reitnauer,
R Borgatti, [......],
I Scheffer,
E C Cooper,
S Ricci,
R Cusmai,
T O Crawford,
R Leroy,
E Andermann,
J W Wheless,
W B Dobyns,
C A Walsh
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ABSTRACT: Mutations in the X-linked gene doublecortin, which encodes a protein with no dear structural homologues, are found in pedigrees in which affected females show "double cortex" syndrome (DC; also known as subcortical band heterotopia or laminar heterotopia) and affected males show X-linked lissencephaly. Mutations in doublecortin also cause sporadic DC in females. To determine the incidence of doublecortin mutations in DC, we investigated a cohort of eight pedigrees and 47 sporadic patients with DC for mutations in the doublecortin open reading frame as assessed by single-stranded conformational polymorphism analysis. Mutations were identified in each of the eight DC pedigrees (100%), and in 18 of the 47 sporadic DC patients (38%). Identified mutations were of two types, protein truncation mutations and single amino acid substitution mutations. However, pedigrees with DC displayed almost exclusively single amino acid substitution mutations, suggesting that patients with these mutations may have less of a reproductive disadvantage versus those patients with protein truncation mutations. Single amino acid substitution mutations were tightly clustered in two regions of the open reading frame, suggesting that these two regions are critical for the function of the Doublecortin protein.
Annals of Neurology 03/1999; 45(2):146-53. · 11.09 Impact Factor
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J G Gleeson,
K M Allen,
J W Fox,
E D Lamperti, S Berkovic,
I Scheffer,
E C Cooper,
W B Dobyns,
S R Minnerath,
M E Ross,
C A Walsh
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ABSTRACT: X-linked lissencephaly and "double cortex" are allelic human disorders mapping to Xq22.3-Xq23 associated with arrest of migrating cerebral cortical neurons. We identified a novel 10 kb brain-specific cDNA interrupted by a balanced translocation in an XLIS patient that encodes a novel 40 kDa predicted protein named Doublecortin. Four double cortex/X-linked lissencephaly families and three sporadic double cortex patients show independent doublecortin mutations, at least one of them a de novo mutation. Doublecortin contains a consensus Abl phosphorylation site and other sites of potential phosphorylation. Although Doublecortin does not contain a kinase domain, it is homologous to the amino terminus of a predicted kinase protein, indicating a likely role in signal transduction. Doublecortin, along with the newly characterized mDab1, may define an Abl-dependent pathway regulating neuronal migration.
Cell 02/1998; 92(1):63-72. · 32.40 Impact Factor
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ABSTRACT: Progressive myoclonus epilepsy (PME) may develop in adult life. We present two patients with PME appearing around the age of 30 years in whom the disorder represented a manifestation of Alzheimer's disease. This diagnosis must be considered in addition to possible Kufs' disease or myoclonic epilepsy with ragged red fibers (MERRF) when PME develops in young adults.
Neurology 01/1998; 49(6):1732-3. · 8.31 Impact Factor
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M E Ross,
K M Allen,
A K Srivastava,
T Featherstone,
J G Gleeson,
B Hirsch,
B N Harding,
E Andermann,
R Abdullah,
M Berg, [......],
J Motté,
A P Mira,
I Scheffer, S Berkovic,
F Scaravilli,
R A King,
D H Ledbetter,
D Schlessinger,
W B Dobyns,
C A Walsh
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ABSTRACT: While disorders of neuronal migration are associated with as much as 25% of recurrent childhood seizures, few of the genes required to establish neuronal position in cerebral cortex are known. Subcortical band heterotopia (SBH) and lissencephaly (LIS), two distinct neuronal migration disorders producing epilepsy and variable cognitive impairment, can be inherited alone or together in a single pedigree. Here we report a new genetic locus, XLIS, mapped by linkage analysis of five families and physical mapping of a balanced X;2 translocation in a girl with LIS. Linkage places the critical region in Xq21-q24, containing the breakpoint that maps to Xq22.3-q23 by high-resolution chromosome analysis. Markers used for somatic cell hybrid and fluorescence in situ hybridization analyses place the XLIS region within a 1 cM interval. These data suggest that SBH and X-linked lissencephaly are caused by mutation of a single gene, XLIS, that the milder SBH phenotype in females results from random X-inactivation (Lyonization), and that cloning of genes from the breakpoint region on X will yield XLIS.
Human Molecular Genetics 05/1997; 6(4):555-62. · 7.64 Impact Factor
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Y M Hart,
F Andermann,
D R Fish,
F Dubeau,
Y Robitaille,
T Rasmussen, S Berkovic,
R Marino,
E M Yakoubian,
K Spillane,
F Scaravilli
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ABSTRACT: Chronic encephalitis and epilepsy (Rasmussen's encephalitis) is a rare progressive disorder of uncertain etiology that usually occurs in children, producing focal epilepsy, hemiparesis, and intellectual deterioration. We identified 13 patients in whom seizures developed in adolescence or adulthood with a pathologic picture of chronic encephalitis. The clinical characteristics were more variable than those occurring in children, with the patients falling into three groups: five patients developed seizures in adulthood, but otherwise showed many resemblances to the childhood form; five developed seizures in adolescence, with similar presentation but rather more benign course than in the younger patients; and three presented with clinical features initially suggestive of a tumor. Occipital onset to the seizures appeared to be more common than in the childhood form, and bilateral disease also occurred.
Neurology 03/1997; 48(2):418-24. · 8.31 Impact Factor
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ABSTRACT: Electrophysiological studies (EEG, evoked potentials, nerve conduction and EMG) in 13 patients with myoclonus epilepsy with ragged red fibres (MERRF) are presented. The most notable findings are the presence of atypical irregular generalized spike and wave discharges arising from an abnormal EEG background (9 patients), focal epileptiform abnormalities (6 patients) most commonly over the occipital regions and giant cortical SEPs (4 of 6 patients tested). Similar findings of disturbed EEG background activity, generalized spike and wave discharges and giant cortical SEPs appear to be shared by the group of diseases characterized by progressive myoclonus epilepsy.
Brain 11/1989; 112 ( Pt 5):1261-76. · 9.46 Impact Factor
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Movement Disorders 02/1989; 4(1):13-7. · 4.51 Impact Factor
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[show abstract]
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ABSTRACT: Focal cortical myoclonus is rare. Obvious causes include tumor or atrophy involving the motor strip, but in some cases no cause is apparent. We present 4 patients who started to have focal myoclonus in childhood. All had focal motor seizures as well, and one had recurrent focal motor status epilepticus. All 4 had a mild progressive hemiparesis. Electrographic investigations showed focal epileptic discharges in the contralateral rolandic areas. Radiological studies were unrevealing, but magnetic resonance showed rolandic lesions in 3 patients. At surgery, abnormally wide gyri were found in the distribution demonstrated by magnetic resonance. The pathological substrate was focal cortical dysplasia. All patients have improved considerably following surgery. These findings suggest that focal myoclonus may be due to a rolandic neuronal migration disorder. Visualization of these lesions by magnetic resonance permits development of a surgical strategy leading to optimal treatment of these medically intractable epileptic disorders.
Annals of Neurology 05/1988; 23(4):317-25. · 11.09 Impact Factor
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ABSTRACT: A retrospective single-blind study assessing the value of magnetic resonance imaging (MRI) in 48 patients treated surgically for temporal lobe epilepsy was carried out. The imaging findings were correlated with the surgical findings in all cases. Abnormal MRI signals were detected in 34 of 48 (71%) epileptic patients and in 3 of 48 (6.2%) normal or disease control subjects. Twelve patients had structural foreign-tissue lesions, all detected by MRI. Of 14 patients with severe gliosis of the neocortex and/or mesial temporal structures, 11 had abnormal MRI scans. In patients with mild or moderate gliosis of mesial temporal structures, 6 of 12 had abnormal MRI scans. These results indicate that MRI is a sensitive technique for localizing foreign-tissue lesions, mesial temporal sclerosis, and gliosis in patients with intractable temporal lobe seizures.
Annals of Neurology 10/1987; 22(3):341-7. · 11.09 Impact Factor
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ME Ross,
KM Allen,
AK Srivastava,
T Featherstone,
JG Gleeson,
B Hirsch,
BN Harding,
E Andermann,
R Abdullah,
M Berg, [......],
J Motte,
AP Mira,
I Scheffer, S Berkovic,
F Scaravilli,
RA King,
DH Ledbetter,
D Schlessinger,
WB Dobyns,
CA Walsh
