A ＂Triple Trouble＂ Case of Facioscapulohumeral Muscular Dystrophy Accompanied by Peripheral Neuropathy and Myoclonic Epilepsy

Background： Facioscapulohumeral muscular dystrophy （FSHD） is characterized by asymmetric muscular deficit of facial, shoulder-girdle muscles, and descending to lower limb muscles, but it exists in several extramuscular manifestations or overlapping syndromes. Herein, we report a ＂complex disease plus＂ patient with FSHD1, accompanied by peripheral neuropathy and myoclonic epilepsy. Methods： Standard clinical assessments, particular auxiliary examination, histological analysis, and molecular analysis were performed through the new Comprehensive Clinical Evaluation Form, pulsed-field gel electrophoresis-based Southern blot, Multiplex Ligation-dependent Probe Amplification （MLPA）, whole exome sequencing （WES）, and targeted methylation sequencing. Results： The patient presented with mild facial weakness, humeral poly-hill sign, scapular winging, peroneal weakness, drop foot, pes cavus, and myoclonic epilepsy. Furthermore, electrophysiology revealed severely demyelinated and axonal injury. The muscle and nerve biopsy revealed broadly fiber Type II grouping atrophy and myelinated nerve fibers that significantly decreased with thin myelinated fibers and onion bulbs changes. Generalized sharp and sharp-slow wave complexes on electroencephalography support the diagnosis toward myoclonic epilepsy. In addition, molecular testing demonstrated a co-segregated 20-kb 4q35-EcoRI fragment and permissive allele A, which corresponded with D4Z4 hypomethylation status in the family. Both the patient＇s mother and brother only presented the typical FSHD but lacked overlapping syndromes. However, no mutations for hereditary peripheral neuropathy and myoclonic epilepsy were discovered by MLPA and WES. Conclusions： The present study described a ＂tripe trouble＂ with FSHD, peripheral neuropathy, and myoclonic epilepsy, adding the spectrum of overlapping syndromes and contributing to the credible diagnosis of atypical phenotype. It would provide a direct clue on medical care and genetic counseling.

Frontier in Neurology Research Beyond Neurodegenerative Diseases

As a guest editor for this special issue of Neurology Diseases in the Chinese Medical Journal （English Edition）, I am pleased to announce a completion of 19 articles （13 research articles, 4 review papers and 2 case reports） which cover a spectrum of research frontier in neurology diseases lbr publication in this issue. These articles provide an update on the state of clinical and basic science research in movement disorders （Huntington disease, Parkinson＇s disease, spinocerebellar ataxias （SCAs）, and Wilson＇s disease）, amyotrophic lateral sclerosis, cerebral vascular disease, epilepsy, infection/immunology diseases, and rare genetic disorders （mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes [MELAS] and facioscapulohumeral muscular dystrophy [FSHD]）. While substantial progress in our understanding of these disorders has been achieved, development of accurate diagnosis procedures and precise treatments remains an unrealized goal. Among them, 5 papers are related to Parkinson＇s disease, which show the promise fbr translational research in identifying genetic, biochemical, electrophysiological and imaging biomarkers, aimed to help better diagnosis and management of this disease.