The cerebellar phenotype of Charcot-Marie-Tooth neuropathy type 4C

Autor: Humberto Skott, Cristina Muntean-Firanescu, Luca Verrecchia, Rayomand Press, Alberto J. Espay, Martin Paucar, Göran Solders, Helena Malmgren, Per Svenningsson, Kristin Samuelsson, Carmen Cananau
Rok vydání: 2019
Předmět:
Zdroj: Cerebellum & Ataxias
Cerebellum & Ataxias, Vol 6, Iss 1, Pp 1-7 (2019)
ISSN: 2053-8871
DOI: 10.1186/s40673-019-0103-8
Popis: Background Friedreich ataxia (FRDA) is the most common familial ataxia syndrome in Central and Southern Europe but rare in Scandinavia. Biallelic mutations in SH3 domain and tetratricopeptide repeats 2 (SH3TC2) cause Charcot-Marie-Tooth disease type 4C (CMT4C), one of the most common autosomal recessive polyneuropathies associated with early onset, slow disease progression and scoliosis. Beyond nystagmus reported in some patients, neither ataxia nor cerebellar atrophy has been documented as part of the CMT4C phenotype. Methods Here we describe a single centre CMT4C cohort. All patients underwent a comprehensive characterization that included physical examination, neurophysiological studies, neuroimaging and genetic testing. In a patient with cerebellar features, an evaluation of the vestibular system was performed. Results All five patients in this cohort harbored the R954X mutation in SH3TC2 suggesting a founder effect. Two patients had been diagnosed as FRDA. One of them, an 80-year-old woman had onset of unsteadiness during childhood leading to gradual loss of mobility. She also had scoliosis and hearing loss. On examination she had generalized muscle atrophy, leg flaccidity, pes cavus, facial myokymia, limb dysmetria, dysarthria and gaze-evoked nystagmus. She exhibited bilateral vestibular areflexia. Neuroimaging demonstrated atrophy in the frontoparietal regions and cerebellar hemispheres. Conclusions CMTC4A may present with a cerebellar phenotype and mimic a flaccid-ataxic form of FRDA. Absence of cardiomyopathy or endocrine abnormalities and lack of pathological dentate iron accumulation in CMT4C distinguish it from FRDA. Electronic supplementary material The online version of this article (10.1186/s40673-019-0103-8) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
Externí odkaz: