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We report the clinical, pathological, and genetic findings of 23 patients in 8 families with hereditary motor and sensory neuropathy (proximal dominant form) (HMSN-P) in Okinawa, Japan. The clinical features were unique with respect to autosomal dominant inheritance, Kennedy-Alter-Sung syndrome-like proximal dominant neurogenic atrophy, obvious sensory involvement, painful muscle cramp, fasciculations, areflexia, and high incidences of elevated creatine kinase levels, hyperlipidemia, and diabetes mellitus. Electrophysiological and pathological studies revealed typical motor and sensory axonal neuropathy, and decreased numbers of anterior born and dorsal ganglion cells, which suggested the presence of neuronopathy in HMSN-P. Genetic linkage studies showed a lod score of 4.04 (two-point analysis) in DNA marker D3S1284. Haplotype analysis showed that the gene locus of the disease was mapped to 3p14.1-q13 bracketed by D3S1285 and D3S1281. In this region, the patients' chromosomes showed an obvious increase in the allele frequency of five markers. One allele in D3S1591 was identical in all patients but had a low frequency in the control population. This finding suggested the presence of linkage disequilibrium and a common origin of this allele in all patients with HMSN-P. The HMSN-P described here is a new clinical entity characterized by unique clinical manifestations and a new gene locus.

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Background Hereditary transthyretin (ATTRv) amyloidosis is a rare, inherited, progressive disease caused by mutations in the transthyretin (TTR) gene. We aimed to assess the efficacy and safety of long-term treatment with patisiran, an RNA interference therapeutic that inhibits TTR production, in patients with ATTRv amyloidosis with polyneuropathy. MethodsThis multi-country, multi-centre, open-label extension (OLE) trial enrolled patients at 43 sites in 19 countries as of 24 September 2018. Patients were eligible if they had completed the phase 3 APOLLO (randomised, double-blind, placebo-controlled [2:1], 18-month study) or phase 2 OLE (single-arm, 24-month study) parent studies and tolerated the study drug. Eligible patients from APOLLO (APOLLO-patisiran [received patisiran during APOLLO] and APOLLO-placebo [received placebo during APOLLO] groups) and the phase 2 OLE (phase 2 OLE patisiran group) studies enrolled in this Global OLE trial and receive patisiran 0•3 mg/kg by intravenous infusion every 3 weeks for up to 5 years. Efficacy assessments include measures of polyneuropathy (modified Neuropathy Impairment Score +7 [mNIS+7]), quality of life, autonomic symptoms, nutritional status, disability, ambulation status, motor function, and cardiac stress. Patients included in the current efficacy analyses are those who had completed 12-month efficacy assessments as of the data cut-off. Safety analyses included all patients who received ≥1 dose of patisiran up to the data cut-off. The Global OLE is ongoing with no new enrolment, and current findings are based on the 12-month interim analysis. The study is registered with ClinicalTrials.gov, NCT02510261.

Three hundred ninety patients who underwent thymectomy for myasthenia gravis (MG) were followed up to investigate the development of associated malignancies. There were 102 patients with thymoma and 288 without thymoma. Malignant neoplasms were detected in ten patients, four of whom already had the tumor at the time MG was diagnosed. Thus, malignancy developed after thymectomy in six patients. Malignant fibrous histiocytoma (MFH) developed in three patients, as well as gastric cancer, gastric leiomyosarcoma, rectal cancer, liver cancer, lung cancer, breast cancer, and thymic carcinoid in one patient each. Nine of the ten malignancies developed in the thymoma group, and only one in the non-thymoma group. The predicted number of patients with malignancy was 2.63 in the thymoma group and 2.65 in the non-thymoma group. Our findings suggest that the presence of thymoma facilitates the occurrence of extrathymic malignancy, and that thymectomy never enhances the occurrence of malignancy but possibly inhibits it.