Autosomal recessive progressive myoclonus epilepsy with ataxia and mental retardation
ABSTRACT We describe two couples of sibs from a southern Italian family affected by epilepsy, myoclonus, mental retardation and slight ataxia. Onset was between 4 and 12 years and the course slowly progressive. The clinical picture suggested the diagnosis of Unverricht-Lundborg disease. Molecular study excluded linkage to EPM1. Other possible causes of progressive myoclonus epilepsy were also excluded.
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ABSTRACT: Unverricht-Lundborg disease (ULD) is the purest and least severe type of progressive myoclonus epilepsy (PME), and is not associated with progressive cognitive deficit. Symptoms stabilize in adulthood, with a varying degree of permanent, often severe handicap that is mostly due to myoclonus. The disorder follows an autosomal recessive transmission pattern, with onset between 8 and 15 years years of age of generalized tonic-clonic or clonic-tonic-clonic seizures, action myoclonus (massive or segmental), photosensitivity, and often ataxia. Prevalence varies, it is highest in certain isolates (Finland, La Réunion Island) and in region with higher levels of inbreeding (Maghreb). ULD is due to a deficit in cystatin B (stefin B), but the mechanisms leading to the clinical symptoms are not well understood. The causative gene, PME1, was identified in 1991 and localized to chromosome 21q22.3. The mutations are mainly expansions of the CCCCGCCCCGCG dodecamer, but less common point mutations were also found. A variant has been recently reported in a Palestinian family, with localization on chromosome 12. The diagnosis of ULD is made on the basis of family history, age at onset, geographical and ethnic context, and on the typical features of myoclonus and epilepsy, in the absence of cognitive and sensory deficits. Neurophysiological evaluation yields interesting, but unspecific results. There are no biological or pathological markers for ULD. Molecular analysis confirms the diagnosis in most patients. Genetic testing for heterozygotes and even prenatal diagnosis are possible, although seldom performed, if the mutation has been identified. In spite of intensive research, ULD has yet to reveal all of its secrets. It remains a quasi “idiopathic“ type of PME, with limited progression. Clinicians and patients are still waiting for an etiologically oriented treatment, which should, ideally, be admnistered early in the course of the disease, if possible before the onset of invalidating symptoms.Revue Neurologique 09/2006; 162(s 8–9):819–826. DOI:10.1016/S0035-3787(06)75084-6 · 0.60 Impact Factor
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ABSTRACT: To define the clinical spectrum and etiology of progressive myoclonic epilepsies (PMEs) in Italy using a database developed by the Genetics Commission of the Italian League against Epilepsy. We collected clinical and laboratory data from patients referred to 25 Italian epilepsy centers regardless of whether a positive causative factor was identified. PMEs of undetermined origins were grouped using 2-step cluster analysis. We collected clinical data from 204 patients, including 77 with a diagnosis of Unverricht-Lundborg disease and 37 with a diagnosis of Lafora body disease; 31 patients had PMEs due to rarer genetic causes, mainly neuronal ceroid lipofuscinoses. Two more patients had celiac disease. Despite extensive investigation, we found no definitive etiology for 57 patients. Cluster analysis indicated that these patients could be grouped into 2 clusters defined by age at disease onset, age at myoclonus onset, previous psychomotor delay, seizure characteristics, photosensitivity, associated signs other than those included in the cardinal definition of PME, and pathologic MRI findings. Information concerning the distribution of different genetic causes of PMEs may provide a framework for an updated diagnostic workup. Phenotypes of the patients with PME of undetermined cause varied widely. The presence of separate clusters suggests that novel forms of PME are yet to be clinically and genetically characterized.Neurology 02/2014; 82(5):405-11. DOI:10.1212/WNL.0000000000000077 · 8.30 Impact Factor