Typical JME Versus Pyknoleptic Absence Persisting with Myoclonic Seizures: Linkage Analyses
Abstract number :
1.053
Submission category :
Year :
2001
Submission ID :
3033
Source :
www.aesnet.org
Presentation date :
12/1/2001 12:00:00 AM
Published date :
Dec 1, 2001, 06:00 AM
Authors :
D. Bai, MD, Epilepsy Genetics/Genomics Lab, CEP, UCLA & VA GLAHS, Los Angeles, CA; M.E. Alonso, MD, National Institute of Neurology & Neurosurgery, Mexico City, Mexico; M.T. Medina, MD, Neurology, National Autonomous University, Tegucigalpa, Honduras; J.N
RATIONALE: Juvenile myoclonic epilepsy (JME) and absence epilepsy are the most common subtypes of idiopathic generalized epilepsy. They overlap in age onset and are often accompanied by grand mal clonic tonic clonic seizures (GM). Myoclonic seizures and absence seizures can appear in the same individual in the same or different age period, and in different members of the same family. Myoclonic seizures may follow the appearance of childhood absences. Our objective is to explore if these two syndromes are controlled by genes in the same chromosome 6p11-12 locus.
METHODS: We divided the families into two groups depending on the phenotype of the proband. Group 1 (typical JME) had probands with adolescent onset myoclonic seizures on awakening, and some had adolescent spanioleptic absences. EEG showed 4-6Hz polyspike wave complexes. Group 2 (pyknoleptic absences) had probands with pyknoleptic childhood or juvenile absences. Grand mal and myoclonic seizures appeared during adolescence. EEGs showed 3Hz spike-wave or 3.5-6Hz spike/polyspike-wave complexes. We analyzed the phenotypes of affected members in the two groups, genotyped each family member with chromosome 6p microsatellites and performed two-point linkage analysis assuming autosomal dominant inheritance with 70% age dependent penetrance.
RESULTS: Group 1 had 67 affected members of which 65% had JME and 6% had absences. Twelve persons (18%) had GM only, while 9 (13%) asymptomatic individuals had EEG polyspike waves. Two-point linkage analysis obtained significant Zmax of 7.47, 5.83 and 4.40 for D6S1573, D6S1960, and D6S1541, respectively, at [theta]m=f=0.00 and 5.77, 5.52 and 3.46 for D6S294, D6S272 and D6S465, respectively, at [theta]m=f=0.10. Group 2 had 34 affected members of whom 59% had pyknoleptic childhood absence epilepsy or pyknoleptic juvenile absence epilepsy. Only 15% had JME. Five individuals had GM only and 4 members were EEG affected only. We obtained significant exclusionary LOD scores of -9.23, -5.55, -7.67, -3.44 and -4.01 for D6S1573, D6S1960, D6S1541, D6S272 and D6S294, respectively, at [theta]m=f=0.00.
CONCLUSIONS: Typical JME is genetically linked to chromosome 6p11-12, but pyknoleptic absence epilepsy that persists with myoclonic seizures is not linked to 6p11-12. A genome scan of families with pyknoleptic absences persisting with myoclonic seizures is now underway.