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Keywords:

  • Temporal lobe epilepsy;
  • Aphasic seizures;
  • Chromosome 10;
  • Linkage;
  • Autosomal dominant

Abstract

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

Summary:  Purpose: To describe the phenotypic expression of a new family with familial lateral temporal lobe epilepsy with aphasic seizures, and to compare the findings with the clinical features of previously reported families linked to chromosome 10q22-q24.

Methods: Medical records were collected from 12 living affected members. The patients underwent a personal interview and a clinical neurologic examination. Results from interictal scalp EEGs and neuroimaging examinations were obtained.

Results: The cardinal ictal symptom was a brief sensory aphasia in eight of the patients. In four, this was accompanied by auditory symptoms, usually in the form of monotonous unformed sounds. Simple partial seizures with psychic or somatosensory seizures also were present. Visual ictal symptoms and complex partial seizures were absent. All patients had generalized tonic–clonic seizures. Magnetic resonance imaging (MRI) or computed tomography (CT) did not reveal morphologic correlates. Improvement with age seemed to occur in many patients. Significant linkage to chromosome 10q22-q24 was established by testing 17 polymorphic microsatellite markers.

Conclusions: The epilepsy of this family appears to represent a variety of autosomal dominant lateral temporal lobe epilepsy. Aphasic seizures and a peculiar seizure-precipitating effect of the activation of speech (initiation or perception) may serve as markers for identifying further families with this phenotype.

Recently various syndromes of nonlesional, localization-related epilepsies with simple inheritance have been described: autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) (1–3), autosomal dominant lateral temporal lobe epilepsy (ADLTLE) (4,5), and autosomal dominant partial epilepsy with variable foci (6). The ictal symptoms are characterized by the respective anatomic localizations of seizure initiation. Onset is usually at a young age, and improvement may occur with time. Most patients become seizure free with standard antiepileptic treatment, but there are exceptions. Both interfamilial and intrafamilial clinical variability is wide. Some family members are afflicted with psychiatric or behavioral abnormalities to a variable degree, particularly in ADNFLE, but the seizures are usually the only or major neurologic abnormality (7).

TLEs, including the familial forms, can be divided into two main categories according to the seizure semiology, one with medial temporal lobe symptoms (8) and one with lateral symptoms (4,5). The clinical expression of the familial TLE of the medial type is similar to the ictal manifestations of mesial temporal sclerosis and consists of autonomic auras, perceptual changes, and psychic and dysmnestic symptoms including déjà vu, usually evolving to complex partial seizures (CPSs) and/or secondary generalization (8). The symptoms of ADLTE usually consist of simple partial seizures (SPSs) with mainly acoustic and sometimes even visual hallucinations (4,5,8–10). Accordingly, this syndrome was designated “autosomal dominant partial epilepsy with auditory features” (ADPEAF) when it was first described (4,9). Recently a small Japanese family with SPSs in the form of aphasic symptoms and secondary generalization was reported (11). We now describe the phenotypic and genetic features of a large Norwegian pedigree with familial partial epilepsy characterized by aphasic as well as auditory ictal symptoms, and discuss them with respect to the previously published families with ADLTE

PATIENTS AND METHODS

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

Clinical data collection

A large Norwegian family comprising 80 members (excluding spouses) of which 17 were affected by epilepsy and three had solitary or uncharacteristic seizures was studied. The family came to our attention through the index patient, IV:5 (Fig. 1), who was referred at the age of 15 years for short attacks of sensory aphasia. He had been treated for recurrent generalized tonic–clonic seizures (GTCs) since age 9 years and had a remarkable family history of epilepsy. To identify relatives with seizures, members of each of the living nuclear families were contacted by telephone by a collaborating key family member, his unaffected sister (IV:4). Six of the affected individuals were dead. Their status was assessed by interviewing the offspring. Twelve affected members agreed to participate after informed consent. Clinical histories were obtained, and clinical neurologic examinations performed. All underwent a semistructured interview focusing on seizure semiology and seizure-precipitating factors. Information from previous medical records was collected, including results from routine interictal electroencephalography (EEG) recordings. Nine patients were examined by magnetic resonance imaging (MRI), and in three, only computed tomography (CT) was available. The CT scans and three of the MRIs had been performed previously. The six MRIs obtained specifically for this study were performed at 1.0 T with T1-, intermediate-, and T2-weighted transverse images, and intermediate-, T2-weighted, and inversion recovery coronal images, as well as T1-weighted sagittal images. In two patients, coronal fluid-attenuated inversion recovery (FLAIR) sequences were performed. Additional inversion recovery, transverse slices through hippocampal structures were obtained in five patients.

image

Figure 1. Pedigree of the Norwegian autosomal dominant lateral temporal lobe epilepsy (ADLTLE) family. Affected individuals are marked by black symbols. A vertical black bar within a symbol characterizes solitary or uncharacteristic seizures. Triangles with numbers attached at their right side indicate several offspring of unknown sex and phenotype. The consanguineous marriage (second cousins) of the parents of V:1 is indicated by double lines. Marker alleles are given in the following order (top to bottom): cen-D10S1686, D10S1427, D10S1744, D10S1687, D10S541, D10S1753, D10S185, D10S1680, D10S1709, D10S198, D10S192, D10S566, D10S1671, D10S597, D10S1731, D10S1683, D10S1711-tel.

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Genotyping

Samples for DNA extraction were collected from 17 family members (including spouses). The microsatellites were amplified by using primers published in the Human Genome Database (http://www.gdb.org). Polymerase chain reaction (PCR) was performed with 10 ng of genomic DNA, 10 pmol of each primer, 200 μM deoxyribonucleoside triphosphate (dNTP), 1–2 mM MgCl2, 50 mM KCl, 10 mM Tris-HCl, 0.5–1 U Taq polymerase (Invitrogen, Groningen, NL) in a total volume of 50 μl. PCR product (2 μl) was mixed with 3 μl loading buffer (95% formamide, 0,25% bromphenol blue). Before loading, the samples were denatured at 95°C for 5 min and snap-chilled on ice. Electrophoresis was carried out on 8% (19:1) denaturing sequencing gels. The gels were run at 50 V/cm for 1–3 h on a S2-Sequencing apparatus (Invitrogen) and than silver-stained. To avoid typing errors, each gel was interpreted by two different investigators who were unaware of the status.

Statistical analysis

Two-point linkage analysis was performed using MLINK of the LINKAGE package (version 5.1) (12) in the FASTLINK implementation (version 4.1p) (13,14), assuming an autosomal dominant disease model. The disease allele frequency in the population and phenocopy rate were set at 0.001. Penetrance was estimated from the pedigree and set at 0.6 (for more details, see Results). Marker allele frequencies were estimated from the independent haplotypes in the pedigree

RESULTS

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

Clinical characteristics

The pedigree includes five generations (Fig. 1). Clinical details were obtained from 12 affected individuals in generations III and IV (Table 1). Mean age at seizure onset was 18 years in the entire family (range, 4–42 years); in generation III, 26 years (range, 17–42); and in generation IV, 11 years (range, 4–22). Environmental risk factors for epilepsy were not present, other than mild head traumas in patients IV:10 and IV:31. None had a history of febrile convulsions. Clinical examinations were normal, and there was no evidence of intellectual disability, dementia, or psychiatric illness. All patients were reported to be right-handed, except IV:10, who was left-handed.

Table 1.  Clinical characteristics of 12 patients with ADTLE
PatientSex (age)Onset age (yr)Seizure typesTreatmentCourse (years since last seizure)
   SleepAwake  
  1. M, male; F, female; SPS, simple partial seizure; GTC, generalized tonic–clonic seizure; LTG, lamotrigine; CBZ, carbamazepine; PB, phenobarbital; PHT, phenytoin; ADTLE, autosomal dominant temporal lobe epilepsy.

III:2F (72)17SPS, GTCPB, PHTGTC (25), SPS persistent
III:5M (58)18GTCSPS, GTCCBZGTC (14), SPS (5)
III:8M (49)25GTCSPSDiscontinuedGTC (17), SPS persistent
III:12F (50)42GTCSPSCBZGTC (7), SPS (7)
III:30F (58)30SPS, GTCNeverGTC (13), SPS persistent
IV:3M (34)4GTCSPSCBZ, VPAGTC (2), SPS persistent
IV:5M (16)9SPS, GTCLTGGTC (2), SPS persistent
IV:9F (31)4GTCSPS, GTCCBZGTC (3), SPS (2)
IV:10M (43)11GTCPB, PHTGTC (3)
IV:24M (44)22GTCSPSPHTGTC (4), SPS (20)
IV:27F (34)13GTCSPSDiscontinuedGTC (13), SPS (13)
IV:31F (26)17GTCSPSLTGGTC (0), SPS persistent

Seizure semiology

GTCs were present in all patients. In seven, they were exclusively sleep related (Table 1). Five had experienced GTCs during wakefulness, all with a simple partial start, and in four with distinct aphasic or auditory features. All except IV:10 (left-handed) reported daytime events compatible with SPSs. These symptoms included characteristic aphasic features in eight patients (Table 2). Loss of comprehension of the spoken word (III:5: “like a foreign language”), often associated with an inability to think clearly and to express oneself, was the cardinal ictal symptom (Table 2). In two patients, this was the only SPS symptom, whereas in III:2, III:12, III:30, and IV:31, it was associated with simple auditory hallucinations in the form of tinnitus or a steady noise. In subject IV:9, it was accompanied by structured hallucinations in the form of music and frightening voices, followed by unilateral somatosensory symptoms with a warm pins-and-needles sensation, particularly in the head, face, and arm, predominantly to the right.

Table 2.  Seizure semiology and interictal EEG and neuroimaging findings in 12 patients with ADTLE
PatientSeizure semiologyInterictal EEGNeuroimaging
 Simple partial seizureAura preceding GTC  
  • GTC, generalized tonic–clonic seizures; L, left; R, right; MRI, magnetic resonance imaging; CT, computed tomography.

  • a

     Precipitation by speech.

  • ADTLE, autosomal dominant temporal lobe epilepsy.

III:2Ear buzzing and inability to understand talking on the radioaSame as partial seizureNormalMRI normal
III:5He hears, but cannot understand spoken words. Feeling that he cannot express himselfSame as partial seizure, but shorterEpisodic, slow activity L frontotemporalMRI normal
III:8Short episodes of ear ringingNo, sleep relatedNormalMRI normal
III:12Loss of speech comprehension, buzzingaNo, sleep relatedNormalMRI normal
III:30Tinnitus, thought arrest, and inability to comprehendaHead buzzingNormalCT normal
IV:3Thought arrest and inability to speak and understandaNo, sleep relatedAs child, side-shifting epileptiform activity; as adult, slow activity L temporooccipitalMRI normal
IV:5Mild vertigo. Loss of speech comprehensionaVertigoSlow activity L frontotemporal with sharp waveMRI normal
IV:9Loss of speech comprehension. Auditory hallucination with humming, music, voices. Warm paresthesias R side (sometimes L?)aAuditory and somatosensorySeveral normal recordings and one with discrete slow activity L temporalMRI normal
IV:10NoneNo, sleep relatedNormalNot performed
IV:24Possibly in the form of short episodes of inability to understand the written word?No, sleep relatedSlow activity L frontotemporal with sharp wavesMRI normal
IV:27Sensation of depersonalization and déjà vuNo, sleep relatedNormal in routine recording, epileptiform activity L temporoparietal in sleep recordingCT normal
IV:31Vertigo. Loss of speech comprehension. Humming soundaNo, sleep relatedNormalMRI: small white-matter lesion

One patient had episodes of psychic symptoms with a déjà vu sensation without auditory manifestations or reduced consciousness, when she felt she was standing outside herself (IV:27). In two patients (IV:5 and IV:31), components of vertigo were present. Both described a queer, brief rotational sensation, but with no tendency to fall. Two other patients had rather vague and uncharacteristic episodic symptoms that were difficult to classify; III:8 reported episodes of tinnitus, and IV:24 remembered moments of inability to understand text when reading during school 20 years ago.

Seizure precipitation

Several patients felt that lack of sleep and stress could provoke seizures. Seven patients reported that aphasic seizures in stressful situations could sometimes be precipitated by the activation of speech (Table 2). Patients III:30, IV:9, and IV:31 could have a seizure when taking the phone and were able to say “just a moment” before starting the conversation after a few seconds. IV:9 reported having them also when her own calls were answered. IV:31 remembered having had multiple attacks during school years when spoken to in class, and this held her back in school. IV:3 had experienced onset of such symptoms when addressed during business meetings. He lost the meaning of the conversation and had to leave the room for a short while to “clear his mind.” III:12 and IV:5 described the SPSs particularly occurring when suddenly spoken to after an interval of silence. In III:2, III:12, and IV:9, they were even triggered by suddenly turning on the radio. III:2 and III:12 had experienced this only when talking was on the program. IV:9 thought she remembered that even loud music could precipitate a SPS, but possibly only when accompanied by singing.

Epilepsy course

In all subjects with both seizure types, the SPSs started several years before the GTCs. All patients, except IV:31, who was recently diagnosed, had been free from GTCs for geqslant R: gt-or-equal, slanted2 years (range, 2–25 years). When all patients were included, mean seizure freedom from GTCs was longer (i.e.,15 years) in generation III (mean age, 57 years) than in generation IV, 4 years (mean age, 34 years), indicating an improvement with age. One patient had never been treated for epilepsy; two had discontinued antiepileptic drugs (AEDs; Table 2).

In six patients, SPSs had not remitted at the time of investigation. Patient III:30 (not treated) had recurring SPSs several months apart. Patient III:2 also had occasional SPSs in spite of AED treatment. Patients IV:3 and IV:5 had frequent SPSs in childhood up to several times per week. At the age of 34 and 16 years, respectively, they still have sporadic SPSs. Their father (III:5) had SPSs at approximately monthly intervals when younger, but they disappeared completely after phenytoin (PHT) was exchanged with carbamazepine (CBZ) 5 years ago. Patients III:12 and IV:27 had only SPSs before receiving AEDs. Patient IV:9 had also had up to one to two partial seizures per week, but had been completely seizure free for 2 years after increase of the CBZ dose.

Subject IV:37 had only one single GTC at age 26 years and was not treated with AEDs. At age 28 years, he was found dead in the morning after going to bed early the preceding night. According to the parents, there were no signs of either drooling, tongue-biting, or voiding. His father's cousin, III:24, who had definite epilepsy, also had a sudden, unexpected death during sleep at about the same age.

EEG and neuroimaging

Most patients had several routine interictal scalp EEG recordings. Epileptiform activity was found in four patients: in three, over the left temporal area, and in one, alternating over both temporal areas at age 10 years. Unspecific slow activity over the left lateral aspects of the brain was found in three of these cases, and in two other patients. Background rhythms were normal in all. Six patients had normal recordings only, and all patients with EEG abnormalities, except one (IV:24), also had EEG recordings within normal limits (Table 2). Brain imaging was performed in 11 patients. Morphologic abnormalities were not demonstrated other than a small white-matter MR lesion in the left parietal region in patient IV:31, which was not considered to be of clinical significance.

Genetic analysis

The segregation pattern of epilepsy in the large pedigree is compatible with autosomal dominant inheritance with reduced penetrance. Affected individuals and obligate carriers had a total of 38 children (only individuals with known phenotype were taken into account), of which 16 had ADLTE, corresponding to a penetrance rate of ∼84%. If relatives of obligate carriers were excluded to avoid possible ascertainment bias, the penetrance was ∼60%. Among parents of affected individuals, six of nine had ADLTE, suggesting a penetrance of ∼66%. However, given the small number of parents, the latter estimate is probably less reliable. For linkage analysis, penetrance levels of both 60 and 80% were used, the latter resulting in slightly higher LOD score values. Only data for the more stringent 60% penetrance level are presented. Table 3 shows significant two-point linkage for several of the 17 chromosome 10 markers analyzed (significance level for a candidate approach, LOD score, >1). Recombination events between markers D10S1427 and D10S1744 as well as between markers D10S1731 and D10S1683 defined the proximal (with respect to the chromosome centromer) and distal border of the interval containing the disease gene in our family. The proximal border is located telomeric to the corresponding border decribed by Poza et al. (5) but centromeric to the one found by Ottman et al. (4). The distal border is located telomeric from the ones previously defined by Ottman et al. (4) and Poza et al. (5). Thus the candidate region for ADLTE on chromosome 10q22-q24 can not be further narrowed down by the linkage results obtained from our family (Fig. 2).

Table 3.  Two-point LOD scores
Marker0.00.050.10.20.30.4lodmaxθ
D10S1686−1.00−0.180.130.280.210.10
D10S1427−1.100.020.120.120.04−0.02
D10S17442.262.001.741.240.760.332.260
D10S16872.992.662.331.671.040.472.990
D10S5412.482.191.911.350.820.362.480
D10S17531.691.471.260.860.490.191.690
D10S1852.952.652.341.701.050.462.950
D10S16801.791.561.340.910.530.221.790
D10S17091.241.070.910.600.350.151.240
D10S1982.562.271.981.410.860.382.560
D10S1921.991.741.491.010.580.231.990
D10S5662.952.632.301.651.030.472.950
D10S16711.861.621.380.910.480.171.860
D10S5871.631.421.210.820.480.211.630
D10S17311.421.221.020.630.300.071.420
D10S1683−0.400.360.510.500.340.15
D10S1711−3.77−1.29−0.81−0.42−0.26−0.15
image

Figure 2. Autosomal dominant lateral temporal lobe epilepsy (ADLTLE) linkage results on chromosome 10q22-q24. Sex-averaged distances (given in cM, centimorgans) were used for map location of polymorphic markers (http://gdbwww.gdb.org). Minimal candidate regions are indicated by black bars and regions of recombination events (maximal candidate regions) by gray bars. A: Polymorphic markers tested in the present study. B: Candidate region described by Poza et al. (5). C: Candidate region described by Ottman et al. (4). B, C: For each boundary, only the two markers flanking the respective recombination event are given. cen, centromeric.

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DISCUSSION

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

Although the phenotype of this family bears strong similarities to the clinical pictures of previously reported ADLTE families (4,5,9,10,15), some differences are apparent. The transmission pattern also is consistent with an autosomal dominant inheritance with incomplete penetrance. The mean age at seizure onset (18 years; range, 4–42 years) was similar to the German family (19 years; range, 11–50 years), but higher than that in the U.S. family (13 years; range, 8–19 years) (4) and lower than that in the Basque patients (24 years; range, 11–40 years) (5). The ictal semiology of our patients varied (Table 2), but the central element was a stereotypic loss of comprehension of the spoken word, as a flash of sensory aphasia (eight patients). This disturbance of auditory perception, along with positive acoustic symptoms, clearly suggests the implication of the lateral, neocortical part of the temporal lobe, usually of the dominant hemisphere. However, medial temporal lobe onset (patient IV:27) and extratemporal lobe onsets, parietal (patients IV:5 and IN:31) or frontal, cannot be ruled out.

Aphasic symptoms were not reported in the other families with proven 10q-linked partial epilepsy, except in one member of the U.S. family who described an aura in which “it would sound like people would be talking backwards or something”(9). However, ictal aphasia was a hallmark in a newly described, small Japanese kindred with familial epilepsy (11). Auditory symptoms were present in six of our 12 patients, in the form of unformed sounds in five and as additional music and voices in one. SPSs seem to start several years ahead of GTCs in this condition, and the aphasic and simple auditory phenomena may easily be misdiagnosed (e.g., in IV:31 as common tinnitus). Auditory auras were the only focal seizure component in the German family (10) and in the three living affected members of the small Italian family with autosomal dominant partial epilepsy reported by Michelucci (15). It also was the most frequent aura in the U.S. family (six of 11) (9), whereas in the Basque patients, it was less common (four of 11) (5). In the latter family, visual symptoms predominated (six of 11). Visual symptoms were rare in the U.S. patients (two of 11) (9) and completely absent in our as well as in the German family (10). Vertiginous sensations also have been a rare symptom in previously described ADLTE series, present in only one member of the U.S. family (9), but in two of our patients. Somatosensory symptoms were a distinct feature in one of our patients (IV:9), but were not described in the other families. CPSs were reported in as many as seven of 11 patients in the U.S. family (9), but in only two of 11 and in one of nine in the Basque and German families, respectively (7,10). In the Italian family, the three affected living patients exclusively had SPSs with secondary generalization (15). There was no evidence of CPSs in our patients. CPSs seem to be a relatively rare manifestation of ADLTE, in contrast to the medial temporal lobe epilepsies. The symptomatogenic zone usually seems to be restricted to the lateral neocortex in these patients and less often spreads to the medial archicortex or limbic structures.

The EEG abnormalities recorded in our patients were usually mild, and focal findings were predominantly left-sided (Table 2). Most patients who had abnormal tracings also had other recordings described as completely normal. In the U.S. family, normal routine EEGs were reported in all examined subjects (9), whereas in the Basque family, two of seven showed epileptiform potentials over the left temporooccipital area; the others were normal. In the present patients, brain imaging or past history gave no clues as to specific causes of epilepsy in agreement with most other reports on ADLTE (4,5,10,15). Seizures were the only neurologic symptom, and according to the current classification (16), this new entity should be classified among the idiopathic localization-related epilepsies. However, it is noteworthy that MRI revealed a neuronal migration disorder (not further specified) in one of the Japanese patients with aphasic seizures (11). One may speculate whether this finding may represent the tip of the iceberg of cytoarchitectonic abnormalities in ADLTE, and that other patients with this syndrome may have more subtle forms of cortical dysgenesis that are beyond the resolution of current neuroimaging methods.

The overall prognosis is reported to be good in the dominantly inherited partial epilepsies (7). GTCs were controlled in all our patients, but pharmacoresistant SPSs were present in 50%. It is noteworthy that two subjects with a history of seizures in this family had a sudden unexpected death.

Five of our patients reported that seizures were sometimes precipitated by the activation of speech, usually when addressed orally or taking the phone, particularly in stressful situations. In two of the four reported Japanese patients with aphasic seizures, it is specified that seizures occurred when “talking on the phone”(11). It was also suggested that two members of the U.S. family had seizures provoked by auditory stimuli (9). Some of our patients felt that it was the initiation to speak that could precipitate a seizure, whereas others believed that it was merely the sudden perception of talking. Different forms of language-induced epilepsy have previously been described. Primary reading epilepsy also is classified among the idiopathic localization-related epilepsies (16). According to Geschwind and Sherwin (17), other forms may involve seizure precipitation by speaking as well as by writing (17).

The significant results obtained by linkage analysis for chromosome 10q22-q24 markers indicate that the epilepsy in our family is probably caused by the same gene as in the U.S., Basque, and German families. Genetic analyses in the latter families revealed linkage to chromosome 10q22-q24, indicating the localization of an unknown epilepsy gene in an overlapping 3-cM region (4,5). Haplotype analysis in the small Italian families also was consistent with this localization (15). The most likely region for an ADLTE gene in our family as defined by recombination events includes the overlapping regions on chromosome 10q22-q24 defined in previous reports (4,5), but does not exclude a more distal localization.

Despite some phenotypic differences, there are impressive similarities in these families. In all of them, simple, auditory ictal symptoms have been present. The U.S. group called this disorder “autosomal dominant partial epilepsy with auditory features (ADPEAF).” However, in many patients, other symptoms from the lateral temporal lobe predominate, indicating that the most important feature is the localization of the epileptogenic zone in this area. In our patients, the aphasic symptoms, the precipitation by speech, along with the prevailing left-sided EEG abnormalities give rise to speculations whether the mutant gene may be specifically coupled to the function of speech. At present, it is difficult to decide whether the most appropriate designation for this epilepsy should reflect the symptoms, the brain area involved, or the localization of the responsible gene. Rather than basing the nomenclature on the variable phenotype, the term 10q-linked partial epilepsy may be relevant. Future genetic studies will show if all the chromosome 10q–linked partial epilepsies are indeed caused by the same gene, or if, as known for other chromosomal regions, more than one epilepsy-causing gene is located in close vicinity (3,18,19). If it is only one gene, it will be interesting to learn which mechanisms are responsible for the observed phenotypic differences.

Conclusions

The epilepsy in our family seems to belong to the spectrum of ADLTE, which is a subgroup of familial TLE. However, brief sensory aphasia is a striking ictal symptom in most of our patients, which has not been reported as a distinctive feature in previous families with linkage to chromosome 10q22-q24. A peculiar seizure-precipitating effect of the activation of speech seems to be present in some patients. Secondarily generalized, nocturnal GTCs are common. Although SPSs and occasional GTCs may persist in adult age, this condition seems to share a good prognosis with most other idiopathic partial epilepsies. Nevertheless, sudden unexpected death occurred in two subjects with a history of seizures in this family. The significant results of linkage analysis indicate that the epilepsy in our family is caused by a mutation in an unknown gene located in the 10q22-q24 region, which was previously implicated in the etiology of ADLTE.

Acknowledgment: We are grateful for the excellent cooperation of the members of this family, particularly for the assistance of individual IV:4. Part of this study was supported by grants from the Deutsche Forschungsgemeinschaft to O.K.S. (SFBTR6006/A5)

REFERENCES

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES
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