Mapping of a Locus for a Familial Autosomal Recessive Idiopathic Myoclonic Epilepsy of Infancy to Chromosome 16p13

Abstract

Myoclonic epilepsies with onset in infancy and childhood are clinically and etiologically heterogeneous. Although genetic factors are thought to play an important role, to date very little is known about the etiology of these disorders. We ascertained a large Italian pedigree segregating a recessive idiopathic myoclonic epilepsy that starts in early infancy as myoclonic seizures, febrile convulsions, and tonic-clonic seizures. We typed 304 microsatellite markers spanning the 22 autosomes and mapped the locus on chromosome 16p13 by linkage analysis. A maximum LOD score of 4.48 was obtained for marker D16S3027 at recombination fraction 0. Haplotype analysis placed the critical region within a 3.4-cM interval between D16S3024 and D16S423. The present report constitutes the first example of an idiopathic epilepsy that is inherited as an autosomal recessive trait.

Explorative two‐locus linkage analysis suggests a multiplicative interaction between the 7q32 and 16p13 myoclonic seizures‐related photosensitivity loci

“…The symptoms start in early infancy as myoclonic seizures, febrile convulsions and tonic-clonic seizures, and with frequent paroxysmal features on IPS [de Falco et al, 2001;Zara et al, 2000]. Some of these features resemble the phenotype observed in our families , suggesting that both share a susceptibility gene at this locus.…”

Early-Onset Progressive Myoclonic Epilepsy With Dystonia Mapping to 16pter-p13.3

“…Locus EIM (myoclonic epilepsy, infantile; MIM 605021) is overlapping with PMED (1.65 -6.04 Mbp, between markers D16S3024 and D16S423) but distinct from it in several aspects. EIM is benign and not progressive but rather decreases in adulthood, the cranial computed tomography scans and magnetic resonance imagings are negative for any detectable brain lesions, and both myoclonia and generalized tonic-clonic seizures (GTCSs) could be controlled with valproate (Zara et al, 2000). The second locus is for susceptibility to photosensitivity or photoparoxysmal response at 16p13 (D16S3395; 2.00 Mbp), which is a common epilepsy-related electroencephalographic trait (Pinto et al, 2005).…”

TBC1D24truncating mutation resulting in severe neurodegeneration

“…MRI findings in another patient were diffuse moderate cerebral atrophy and ventricular enlargement at 14 months of age, and severe diffuse cerebral atrophy with secondary ventricular enlargement at 37 months, indicating significant progression of the encephalopathy 7. In contrast, MRI findings in the Italian patients were normal 5. The findings in the Arab patient that was investigated were interpreted as thickened cortex in the frontal poles with loss of grey-white matter definition that was consistent with a developmental malformation 4.…”

“…Recessive TBC1D24 mutations were reported in two families afflicted with different diseases 3 4. An Italian family was afflicted with familial infantile myoclonic epilepsy (FIME; MIM 605021) characterised by myoclonic and generalised tonic-clonic seizures, photosensitivity, and normal neurological and mental development 3 5 6. An Arab family had focal epilepsy and intellectual disability syndrome associated with subtle cortical thickening that was most obvious in the anteromesial frontal areas.…”