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Are c.436G>A mutations less severe forms of Lafora disease? A case report.

Lanoiselée HM, Genton P, Lesca G, Brault F, De Toffol B - Epilepsy Behav Case Rep (2014)

Bottom Line: After 5 years of evolution, the patient only has moderate cognitive impairment.Some NHLRC1 mutations, particularly c.436G>A, are associated with a slower clinical course, but there are conflicting data in the literature.This case strengthens the hypothesis that the c.436G>A mutation in the NHLRC1 gene leads to less severe phenotypes and late-onset disease.

View Article: PubMed Central - PubMed

Affiliation: Service de Neurologie, CHU de Tours, INSERM U 930, France.

ABSTRACT
Lafora disease is a form of progressive myoclonic epilepsy with autosomal recessive transmission. Two genes have been identified so far: EPM2A and NHLRC1, and a third gene, concerning a pediatric onset subform, has been recently proposed. We report the case of a 23-year-old woman of Turkish origin with an unusual disease course. Clinical onset was at the age of 19 years with tonic-clonic seizures, followed by cognitive impairment; EEG was in favor of Lafora disease, and the mutation c.436G>A (a missense mutation substituting aspartic acid in asparagine) in the NHLRC1 gene confirmed this diagnosis. After 5 years of evolution, the patient only has moderate cognitive impairment. Some NHLRC1 mutations, particularly c.436G>A, are associated with a slower clinical course, but there are conflicting data in the literature. This case strengthens the hypothesis that the c.436G>A mutation in the NHLRC1 gene leads to less severe phenotypes and late-onset disease.

No MeSH data available.


Related in: MedlinePlus

Mrs. C.'s EEG (10 μV/mm, 0.3 s, 70 Hz, longitudinal assembly). We can observe a slow background of theta frequency with bursts of diffuse spike and polyspike–waves.
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f0005: Mrs. C.'s EEG (10 μV/mm, 0.3 s, 70 Hz, longitudinal assembly). We can observe a slow background of theta frequency with bursts of diffuse spike and polyspike–waves.

Mentions: We are reporting the case of a 23-year-old woman of Turkish origin. She had no particular medical history during childhood and adolescence. Her parents were cousins. At the age of 20, she experienced for the first time generalized tonic–clonic seizures during her fifth month of pregnancy, which were treated with lamotrigine and clobazam. Seizures persisted with a frequency of one per month until delivery. Cerebral MRI and standard blood tests were normal. EEG recordings showed a slow background with generalized spikes and spike–waves (Fig. 1). After delivery, levetiracetam was added because seizures were not well controlled. When she was 21, the patient presented the first signs of cognitive impairment. Neuropsychological evaluation showed a frontal syndrome associated with an anomic aphasia and memory impairment. Video-EEG made in 2010 showed theta waves and delta waves of large amplitude in anterior regions, with a 2-Hz frequency, which decreased with eyes opening and increased with hyperpnea, and short bursts of generalized spikes and spike–waves. Lamotrigine was stopped, levetiracetam was decreased, and zonisamide was introduced. One month after these modifications, seizure frequency decreased (she had one seizure between March and June 2010). Progressive myoclonic epilepsy was suggested. Mutation screening was performed in the EPM2A and NHLRC1 genes as previously reported [5]. The c.436>A substitution, leading to a change of a highly conserved aspartic acid to asparagine in codon 146 in the NHLRC1 gene at a homozygote state, was detected. At the age of 22, cognitive evaluation showed progressive worsening, with alteration of memory, language, attention, and executive functions.


Are c.436G>A mutations less severe forms of Lafora disease? A case report.

Lanoiselée HM, Genton P, Lesca G, Brault F, De Toffol B - Epilepsy Behav Case Rep (2014)

Mrs. C.'s EEG (10 μV/mm, 0.3 s, 70 Hz, longitudinal assembly). We can observe a slow background of theta frequency with bursts of diffuse spike and polyspike–waves.
© Copyright Policy - CC BY-NC-SA
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4307960&req=5

f0005: Mrs. C.'s EEG (10 μV/mm, 0.3 s, 70 Hz, longitudinal assembly). We can observe a slow background of theta frequency with bursts of diffuse spike and polyspike–waves.
Mentions: We are reporting the case of a 23-year-old woman of Turkish origin. She had no particular medical history during childhood and adolescence. Her parents were cousins. At the age of 20, she experienced for the first time generalized tonic–clonic seizures during her fifth month of pregnancy, which were treated with lamotrigine and clobazam. Seizures persisted with a frequency of one per month until delivery. Cerebral MRI and standard blood tests were normal. EEG recordings showed a slow background with generalized spikes and spike–waves (Fig. 1). After delivery, levetiracetam was added because seizures were not well controlled. When she was 21, the patient presented the first signs of cognitive impairment. Neuropsychological evaluation showed a frontal syndrome associated with an anomic aphasia and memory impairment. Video-EEG made in 2010 showed theta waves and delta waves of large amplitude in anterior regions, with a 2-Hz frequency, which decreased with eyes opening and increased with hyperpnea, and short bursts of generalized spikes and spike–waves. Lamotrigine was stopped, levetiracetam was decreased, and zonisamide was introduced. One month after these modifications, seizure frequency decreased (she had one seizure between March and June 2010). Progressive myoclonic epilepsy was suggested. Mutation screening was performed in the EPM2A and NHLRC1 genes as previously reported [5]. The c.436>A substitution, leading to a change of a highly conserved aspartic acid to asparagine in codon 146 in the NHLRC1 gene at a homozygote state, was detected. At the age of 22, cognitive evaluation showed progressive worsening, with alteration of memory, language, attention, and executive functions.

Bottom Line: After 5 years of evolution, the patient only has moderate cognitive impairment.Some NHLRC1 mutations, particularly c.436G>A, are associated with a slower clinical course, but there are conflicting data in the literature.This case strengthens the hypothesis that the c.436G>A mutation in the NHLRC1 gene leads to less severe phenotypes and late-onset disease.

View Article: PubMed Central - PubMed

Affiliation: Service de Neurologie, CHU de Tours, INSERM U 930, France.

ABSTRACT
Lafora disease is a form of progressive myoclonic epilepsy with autosomal recessive transmission. Two genes have been identified so far: EPM2A and NHLRC1, and a third gene, concerning a pediatric onset subform, has been recently proposed. We report the case of a 23-year-old woman of Turkish origin with an unusual disease course. Clinical onset was at the age of 19 years with tonic-clonic seizures, followed by cognitive impairment; EEG was in favor of Lafora disease, and the mutation c.436G>A (a missense mutation substituting aspartic acid in asparagine) in the NHLRC1 gene confirmed this diagnosis. After 5 years of evolution, the patient only has moderate cognitive impairment. Some NHLRC1 mutations, particularly c.436G>A, are associated with a slower clinical course, but there are conflicting data in the literature. This case strengthens the hypothesis that the c.436G>A mutation in the NHLRC1 gene leads to less severe phenotypes and late-onset disease.

No MeSH data available.


Related in: MedlinePlus