Progressive myoclonus epilepsies (PME) are a group of rare disorders that were initially characterized into three groups on pathological grounds: Lafora disease, lipidoses, and the 'degenerative' forms. 'Degenerative' referred to forms where light microscopy of the brain revealed only neuronal loss and gliosis, without evidence of neuronal storage. With improved pathological, biochemical and clinical analyses, and application of molecular genetics, numerous specific forms of PME have been identified. All are characterized by myoclonus, epilepsy and progressive neurological degeneration. Unverricht-Lundborg disease (ULD) and myoclonic epilepsy with ragged-red fibers (MERRF) are the most common degenerative forms.
El-Shanti et al. (2006) studied a consanguineous Jordanian family with four sibs who suffered from ataxia at the age of 15 months, followed by juvenile onset progressive action tremor at the age of four years and atonic seizures at the age of 8 to 10 years. Genome-wide screening for linkage was employed and fine mapping of the region containing the disease locus was performed. Haplotype analysis delineated a minimal 18.67-cM (23-Mb) pericentromeric region on chromosome 12. Brain MRI was negative for cerebellar hypoplasia and cognitive function was spared. The seizures and tremors were controlled through medication. None of the patients experienced frank myoclonic seizures proposing that the action tremor was linked to appendicular ataxia instead of action myoclonus. The tremor was initiated with fine movement throughout the early process of the disorder, deterioration occurred as the hand approached the target, and persisted for a few seconds following reaching the target. El-Shanti et al. (2006) suggested the possibility that tremor composed of two components that consisted of ataxia tremor and action myoclonus. Bassuk et al. (2008) noted that affected members of the family reported by El-Shanti et al. (2006) had developed progressive myoclonic seizures, and that some patients had also developed upward gaze palsy.
Berkovic et al. (2005) studied 21 members of an Arab family residing in the Western Galilee region since the 12th century, examined the patients' DNA and analyzed the complex consanguineous relationships. Eight affected subjects presenting four males from four sibships were uncovered while no affected subjects were found within earlier generations. Berkovic et al. (2005) went back six generations but was not able to identify the single ancestor who gave rise to all four affected sibships. Subjects were aged 17 to 37 years and mean age of seizure onset was 7.3 years (range 5-10 years). Five patients demonstrated myoclonic seizures, one patient revealed tonic-clonic seizures and two patients showed both seizures. The parents of four patients stated delayed walking during infancy and struggle in walking or running throughout childhood, consistent with ataxia, before the onset of seizures. Myoclonic seizures were provoked by sunlight. The disorder was progressive and resulted in three patients being bound to a wheelchair. No significant progressive dementia was found and the brain MRI of one patient revealed normal scan. Berkovic et al. (2005) proposed that the locus on chromosome 12 presented a novel form of progressive myoclonus epilepsy (PME) and assigned the locus as EPM1B.
Straussberg et al. (2005) portrayed a consanguineous Arab family with eight affected sibs who suffered from early-onset ataxia, dysarthria, myoclonic, generalized tonic-clonic seizures, upward gaze palsy, extensor plantar reflexes, sensory neuropathy, and normal cognition. The onset of progressive ataxia was recorded around the age of four years. The two older sibs, aged 11 and 9 years, developed myoclonic and generalized tonic-clonic seizures that were photosensitive. Meanwhile, the youngest sibling did not develop seizures at the age of four years. All patients experienced clinical characteristics such as tremor, dysmetria, impaired vibration and position sense, and extensor plantar responses. Straussberg et al. (2005) performed genetic linkage analysis which excluded the known loci for autosomal recessive ataxia.