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. 2018 Jan 23:8:503.
doi: 10.7916/D85155WJ. eCollection 2018.

Familial Cortical Myoclonic Tremor and Epilepsy, an Enigmatic Disorder: From Phenotypes to Pathophysiology and Genetics. A Systematic Review

Tom van den Ende  1 , Sarvi Sharifi  1 , Sandra M A van der Salm  2   3 , Anne-Fleur van Rootselaar  1
Affiliations

Familial Cortical Myoclonic Tremor and Epilepsy, an Enigmatic Disorder: From Phenotypes to Pathophysiology and Genetics. A Systematic Review

Tom van den Ende et al. Tremor Other Hyperkinet Mov (N Y). .

Abstract

Background: Autosomal dominant familial cortical myoclonic tremor and epilepsy (FCMTE) is characterized by distal tremulous myoclonus, generalized seizures, and signs of cortical reflex myoclonus. FCMTE has been described in over 100 pedigrees worldwide, under several different names and acronyms. Pathological changes have been located in the cerebellum. This systematic review discusses the clinical spectrum, treatment, pathophysiology, and genetic findings.

Methods: We carried out a PubMed search, using a combination of the following search terms: cortical tremor, myoclonus, epilepsy, benign course, adult onset, familial, and autosomal dominant; this resulted in a total of 77 studies (761 patients; 126 pedigrees) fulfilling the inclusion and exclusion criteria.

Results: Phenotypic differences across pedigrees exist, possibly related to underlying genetic differences. A "benign" phenotype has been described in several Japanese families and pedigrees linked to 8q (FCMTE1). French patients (5p linkage; FCMTE3) exhibit more severe progression, and in Japanese/Chinese pedigrees (with unknown linkage) anticipation has been suggested. Preferred treatment is with valproate (mind teratogenicity), levetiracetam, and/or clonazepam. Several genes have been identified, which differ in potential pathogenicity.

Discussion: Based on the core features (above), the syndrome can be considered a distinct clinical entity. Clinical features may also include proximal myoclonus and mild progression with aging. Valproate or levetiracetam, with or without clonazepam, reduces symptoms. FCMTE is a heterogeneous disorder, and likely to include a variety of different conditions with mutations of different genes. Distinct phenotypic traits might reflect different genetic mutations. Genes involved in Purkinje cell outgrowth or those encoding for ion channels or neurotransmitters seem good candidate genes.

Keywords: Familial; cortical; epilepsy; genetics; myoclonus; tremor.

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Conflict of interest statement

Funding: None. Conflicts of Interest: The authors report no conflicts of interest. Ethics Statement: Not applicable for this category of article.

Figures

Figure 1
Figure 1. Article Selection Flowchart. Literature search for the identification of new pedigrees, genetic/linkage or imaging studies since our last review.1 Thirty-three articles were eligible for analysis: 17 reported on clinical and electrophysiology findings with or without linkage analysis, nine reported on neuroimaging, and seven reported on new potential pathogenic mutations. Abbreviations: DAT-SPECT, Dopamine Transporter, Single Photon Emission Computed Tomography; DTI, Diffusion Tensor Imaging; FCMTE, Familial Cortical Myoclonus Tremor And Epilepsy; fMRI, Functional Magnetic Resonance Imaging; 1H-MRS, Proton Magnetic Resonance Spectroscopy; VBM, Voxel Based Morphometry.
See this image and copyright information in PMC

References

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