The aim of this article is to report on an early-onset AD patient associated with the rare pathogenic variant PSEN1 (Leu85Pro) presenting as a possible corticobasal syndrome with asymmetric limb apraxia, parkinsonian signs, and myoclonus.
All of these factors may be genetically determined, but the greater hyperexcitability underlying more severe seizures and myoclonus at onset may also play a role by increasing cell damage due to reduced cystatin B activity.
Myoclonus and seizures were the most common additional neurological features; individuals with myoclonus (40 [47%] with PSEN1 mutations and 12 [33%] with APP mutations) were significantly more likely to develop seizures (p=0·001 for PSEN1; p=0·036 for APP), which affected around a quarter of the patients in each group (20 [24%] and nine [25%], respectively).
Even though the vast majority of patients with EPM1 have a uniform genetic mutation, the actual size of the longer CSTB expansion mutation allele is likely to have a modulating effect on the age at disease onset, myoclonus severity, and cortical neurophysiology.
Presenilin 1 (PSEN1) gene mutations deterministic for Alzheimer's disease (AD) are associated with marked heterogeneity in clinical phenotype, with behavioral and psychiatric features, parkinsonism, myoclonus, epileptic seizures, spastic paraparesis, frontal behavioral changes suggestive of the phenotype of frontotemporal dementia, aphasia, and cerebellar ataxia being described as well as cognitive decline.
Ectopic white matter neurons, a developmental abnormality that may be caused by the PSEN1S169L mutation in a case of familial AD with myoclonus and seizures.
Cystatin B mutations are now known to account for both Mediterranean myoclonus and for "Baltic" myoclonus, described mainly from Finland, thus solving a long-term controversy and proving that these two disorders are one single disease entity.
Linkage analyses have shown that the genes for both these forms of myoclonus are closely linked to 21q22.3 DNA markers, suggesting that they are caused by mutations at the same locus (EPM1).
This family was characterized by relatively late onset (mean age at 50 years) in familial AD with PS-1 gene mutation and by absence of myoclonus, seizure or paratonia.
Progressive myoclonus epilepsy type 1 (EPM1, also known as Unverricht-Lundborg disease) is an autosomal recessive disorder characterized by progressively worsening myoclonic jerks, frequent generalized tonic-clonic seizures, and a slowly progressive decline in cognition.
Mutations in Proline-rich Transmembrane Protein 2 (PRRT2) have been primarily associated with individuals presenting with infantile epilepsy, including benign familial infantile epilepsy, benign infantile epilepsy, and benign myoclonus of early infancy, and/or with dyskinetic paroxysms such as paroxysmal kinesigenic dyskinesia, paroxysmal non-kinesigenic dyskinesia, and exercise-induced dyskinesia.
A focal motor seizure phenomenologically manifested as a defined movement disorder in 29% of the patients from a consecutive video-EEG documented cohort as per consensus among experts: myoclonus and dystonia (10 and 9 cases, respectively) were the most common movement disorders, followed by chorea (4), stereotypies (3) myoclonus-dystonia (2), and tremor (1).
Fatal familial insomnia (FFI), or familial selective thalamic degeneration with a mutation at codon 178 of the prion protein (PrP) gene, is a rapidly progressive autosomal dominant disease characterized by progressive insomnia, dysautonomia, and myoclonus.
The plaque type prion diseases showed a long clinical course without myoclonus and periodic synchronous discharges, and the major PrP accumulation sites were extracellular PrP plaques.
We identified three new de novo missense variants in KCNC1 in five unrelated individuals causing different phenotypes featuring either isolated nonprogressive myoclonus (p.Cys208Tyr), intellectual disability (p.Thr399Met), or epilepsy with myoclonic, absence and generalized tonic-clonic seizures, ataxia, and developmental delay (p.Ala421Val, three patients).
Moreover, heterozygous de novo frame-shift mutations in the C-terminal domain of KIF5A are associated with neonatal intractable myoclonus, a neurodevelopmental syndrome.