title: Charcot–Marie–Tooth disease type 2J with MPZ Thr124Met  mutation: clinico-electrophysiological and MRI study of a family.
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.
authors.affiliation: Service of Radiology, University Hospital Marqués de Valdecilla, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, University of Cantabria, 39008 Santander, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Gallardo
authors.forename: Antonio
authors.initials: A
authors.lastname: García
authors.forename: César
authors.initials: C
authors.lastname: Ramón
authors.forename: Elías
authors.initials: E
authors.lastname: Maraví
authors.forename: Jon
authors.initials: J
authors.lastname: Infante
authors.forename: Itziar
authors.initials: I
authors.lastname: Gastón
authors.forename: Ángel
authors.initials: Á
authors.lastname: Alonso
authors.forename: Onofre
authors.initials: O
authors.lastname: Combarros
authors.forename: Peter
authors.initials: P
authors.lastname: De Jonghe
authors.forename: José
authors.initials: J
authors.lastname: Berciano
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics; D002607:Charcot-Marie-Tooth Disease / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010750:Phosphoproteins / Q000235:genetics*; D011237:Predictive Value of Tests
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C115628:MPZL1 protein, human; D010750:Phosphoproteins