A novel pedigree with familial cortical myoclonic tremor and epilepsy (FCMTE): Clinical characterization, refinement of the FCMTE2 locus, and confirmation of a founder haplotype

Authors

  • Laura Licchetta,

    1. IRCCS Institute of Neurological Sciences of Bologna, Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy
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  • Tommaso Pippucci,

    1. Medical Genetics Unit, Department of Gynaecological, Obstetric and Paediatric Sciences, Polyclinic Sant'Orsola-Malpighi, University of Bologna, Bologna, Italy
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  • Francesca Bisulli,

    Corresponding author
    1. IRCCS Institute of Neurological Sciences of Bologna, Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy
    • Address correspondence to Francesca Bisulli, IRCCS Istituto delle Scienze Neurologiche, Department of Neurological Sciences, University of Bologna, Via Altura 3, Bologna, Italy. E-mail: francesca.bisulli@unibo.it

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  • Gaetano Cantalupo,

    1. Child Neuropsychiatry Unit, Department of Neuroscience, University-Hospital of Parma, Parma, Italy
    2. Department of Life and Reproduction Sciences, University of Verona, Verona, Italy
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  • Pamela Magini,

    1. Medical Genetics Unit, Department of Gynaecological, Obstetric and Paediatric Sciences, Polyclinic Sant'Orsola-Malpighi, University of Bologna, Bologna, Italy
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  • Lara Alvisi,

    1. IRCCS Institute of Neurological Sciences of Bologna, Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy
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  • Sara Baldassari,

    1. Medical Genetics Unit, Department of Gynaecological, Obstetric and Paediatric Sciences, Polyclinic Sant'Orsola-Malpighi, University of Bologna, Bologna, Italy
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  • Paolo Martinelli,

    1. IRCCS Institute of Neurological Sciences of Bologna, Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy
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  • Ilaria Naldi,

    1. IRCCS Institute of Neurological Sciences of Bologna, Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy
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  • Nicola Vanni,

    1. Department of Neuroscience, Institute G. Gaslini, University of Genoa, Genoa, Italy
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  • Rocco Liguori,

    1. IRCCS Institute of Neurological Sciences of Bologna, Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy
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  • Marco Seri,

    1. Medical Genetics Unit, Department of Gynaecological, Obstetric and Paediatric Sciences, Polyclinic Sant'Orsola-Malpighi, University of Bologna, Bologna, Italy
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  • Paolo Tinuper

    1. IRCCS Institute of Neurological Sciences of Bologna, Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy
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Errata

This article is corrected by:

  1. Errata: Erratum Volume 54, Issue 9, 1709, Article first published online: 6 September 2013

Summary

Purpose

We describe the clinical, neurophysiologic, and genetic features of a new, large family with familial cortical myoclonic tremor and epilepsy (FCMTE).

Methods

Reliable clinical information was obtained on the 127 members. Thirty-one collaborative individuals were assessed by a detailed clinical interview and a complete neurologic examination. A polygraphic study was conducted in 15 patients, back-averaging analysis and somatosensory evoked potentials with C-reflex study in four. The genetic study investigated 30 subjects with microsatellite markers at three loci on chromosomes 8q (FCMTE1), 2p (FCMTE2), and 5p (FCMTE3).

Key Findings

The pedigree included 25 affected members (M/F: 9/16). We studied 16 of the 19 living affected members (M/F: 5/11; mean age 47.8 years). Cortical myoclonic tremor (CMT) was associated with generalized seizures in 10 patients (62.5%). The mean age at onset of CMT and seizures was 28.1 and 33.8 years, respectively. Four patients (25%) reported a slow progression of CMT, with severe gait impairment in one. Psychiatric disorders of variable severity recurred in 37.5% of cases. Rhythmic bursts at 7–15 Hz were recorded in all 11 affected members tested. Additional neurophysiologic investigations disclosed a cortical origin of myoclonus in all patients tested. Generalized epileptiform discharges were recorded in 25% of cases, and a photoparoxysmal response in 31%. Genetic analysis established linkage to the FCMTE2 locus on chromosome 2p11.1-2q12.2 (OMIM 607876) and narrowed the critical interval to a 10.4 Mb segment. Haplotype analysis in the present family identified a founder haplotype identical to that previously observed in families from the same geographic area.

Significance

This study confirms evidence of a founder effect in Italian families and reduces the number of positional candidate genes in the FCMTE2 locus to 59, thereby contributing to future gene identification by Next Generation Sequencing approaches.

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