Apical left ventricular myocardial dysfunction is an early feature of cardiac involvement in myotonic dystrophy type 1.

INTRODUCTION: Left ventricular (LV) dysfunction is a major prognostic determinant in myotonic dystrophy type 1 (DM1). Therefore, markers of early-stage LV impairment may be useful. The aim of this study was to evaluate 2D echocardiographic LV strain in a cohort of DM1 patients with preserved left ventricular ejection fraction (LVEF) and to compare the results with matched controls. METHODS: This prospective single-center study included 33 consecutive DM1 patients between February 2014 and February 2015. Mean age was 38.2±12.9 years, and 17 (52%) were males. Exclusion criteria were LVEF <55%, QRS >120 milliseconds, history of atrial fibrillation, and presence of a pacemaker with ventricular pacing. DM1 patients were matched to healthy controls according to sex and age. RESULTS: DM1 patients showed significant impairment of global longitudinal strain (GLS) as compared to controls (-18.0±1.9 vs -19.1±2.4; P=.03), characterized by a marked alteration at the apex (-20.0±3.3 vs -22.7±3.1; P<.001). DM1 patients had also global radial strain impairment (20.0±9.8 vs 27.5±14.9; P=.024) compared to controls while global circumferential strain was not statistically different between groups (P=.94). Intra- and inter-observer analysis showed good reproducibility of GLS. CONCLUSION: Despite preserved LVEF, DM1 patients exhibited significantly altered LV GLS, particularly at the apex, as compared with controls. The detection of impaired myocardial deformation at early stages of the disease might help to screen high-risk patients who need closer follow-up.

Genotype-phenotype correlations in Charcot-Marie-Tooth disease type 2 caused by mitofusin 2 mutations.

BACKGROUND: Mutations in the gene encoding mitofusin 2 (MFN2) cause Charcot-Marie-Tooth disease type 2 (CMT2), with heterogeneity concerning severity and associated clinical features. OBJECTIVE: To describe MFN2 mutations and associated phenotypes in patients with hereditary motor and sensory neuropathy (HMSN). DESIGN: Direct sequencing of the MFN2 gene and clinical investigations of patients with MFN2 mutations. SETTING: Molecular genetics laboratory of a university hospital and the Limoges National Referral Center for Rare Peripheral Neuropathies. PATIENTS: One hundred fifty index patients with HMSN and a median motor nerve conduction velocity of 25 m/s or greater and without mutations in the genes encoding connexin 32 and myelin protein zero. MAIN OUTCOME MEASURES: Results of genetic analyses and phenotypic observations. RESULTS: Twenty different missense mutations were identified in 20 index patients. Mutation frequency was 19 of 107 (17.8%) in patients with CMT2 and 1 of 43 (2.3%) in patients with a median motor nerve conduction velocity less than 38 m/s. Four patients had proven de novo mutations, 8 families had autosomal dominant inheritance, and 3 had autosomal recessive inheritance. The remaining 5 patients were sporadic cases with heterozygous mutations. Phenotypes varied from mild forms to early-onset severe forms. Additional features were encountered in 8 patients (32%). Six patients underwent sural nerve biopsy: electronic microscopy showed prominent mitochondrial abnormalities on longitudinal sections. CONCLUSIONS: MFN2 mutations are a frequent cause of CMT2, with variable severity and either dominant or recessive inheritance. MFN2 gene testing must be a first-line analysis in axonal HMSN irrespective of the mode of inheritance or the severity of the peripheral neuropathy.