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Charcot–Marie–Tooth disease type 2J with MPZ Thr124Met mutation: clinico-electrophysiological and MRI study of a family

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Abstract

The purpose of the present study was to describe clinico-electrophysiological features and lower limb muscle MRI findings in a CMT2J pedigree due to MPZ Thr124Met mutation. We examined the proband, aged 56 years, and her affected daughter and son, aged 30 and 29 years. Disease severity in terms of ability to walk and run was established using a nine-point functional disability scale (FDS). We administered the CMT neuropathy score (CMTNS) based on patient’s symptoms, neurologic examination and neurophysiologic testing. All three patients had non-symptomatic Adie’s pupil. The proband and her son presented with late-onset lower limb sensorimotor neuropathy and pes cavus; the proband’s daughter had no signs of polyneuropathy. FDS score was 4 in the proband, 2 in her son, and 0 (normal) in her daughter. In both symptomatic patients, electrophysiological study showed a pattern of length-dependent axonal neuropathy mainly involving lower limb nerves; this was normal in the other patient. CMTNS was 18 in the proband, 12 in her son, and 0 (normal) in her daughter. MRI of foot and leg musculature was normal in the proband’s daughter, whereas the other two patients showed massive fatty atrophy of intrinsic foot musculature, extensive and diffuse fatty atrophy of leg muscles in the proband, and mild distally accentuated fatty infiltration of calf muscles in her son. Muscle edema, detected only in the proband’s son, was present in 7 out of 22 (33%) of visualized leg muscles, whereas contrast enhancement occurred in 6 of them. The reported mutation may manifest with either isolated Adie’s pupil or pupil abnormalities with late-onset sensorimotor length-dependent axonal polyneuropathy, though the presence of pes cavus might indicate an earlier onset. MRI examination helps to delineate an accurate extent of muscle involvement in the disease.

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Acknowledgments

We thank Marta de la Fuente for secretarial help and John Hawkins for stylistic revision. This study was supported by CIBERNED and FIS Grant PI07/132E. Also supported by University of Antwerp, the Fund for Scientific Research (FWO-Flanders), the Medical Foundation Queen Elisabeth (GSKE), the “Association Belge contre les, Maladies Neuromusculaires” (ABMM), and the Interuniversity Attraction Poles P6/43 program of the Belgian Federal Science Policy Office (BELSPO).

Conflicts of interest statement

The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Service of Radiology, University Hospital “Marqués de Valdecilla”, “Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED)”, University of Cantabria, 39008, Santander, Spain

    Elena Gallardo

  2. Service of Clinical Neurophysiology, University Hospital “Marqués de Valdecilla”, CIBERNED, University of Cantabria, 39008, Santander, Spain

    Antonio García

  3. Service of Neurology, University Hospital “Marqués de Valdecilla”, CIBERNED, University of Cantabria, 39008, Santander, Spain

    César Ramón, Jon Infante, Onofre Combarros & José Berciano

  4. Service of Neurology, “Virgen del Camino” Hospital, Pamplona, Spain

    Elías Maraví & Itziar Gastón

  5. Service of Genetics, “Virgen del Camino” Hospital, Pamplona, Spain

    Ángel Alonso

  6. Neurogenetics Group, VIB Department of Molecular Genetics, Neurogenetics Laboratory, Institute Born-Bunge, University of Antwerp, Antwerpen, Belgium

    Peter De Jonghe

  7. Department of Neurology, University Hospital Antwerpen, Antwerpen, Belgium

    Peter De Jonghe

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  1. Elena Gallardo
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Correspondence to José Berciano.

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Gallardo, E., García, A., Ramón, C. et al. Charcot–Marie–Tooth disease type 2J with MPZ Thr124Met mutation: clinico-electrophysiological and MRI study of a family. J Neurol 256, 2061–2071 (2009). https://doi.org/10.1007/s00415-009-5251-y

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