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Purpose of review Muscle pain syndromes are extremely frequent cause of chronic disability, and a muscle biopsy is often performed to achieve a diagnosis when myalgia has a myopatic origin. Instead, the role of muscle biopsy in fibromyalgia is controversial. This review examines the reported studies with the objective to evaluate if some changes exist in the muscle, if these changes produce pain and if muscle biopsy is helpful in diagnostic flowchart of fibromyalgia. Recent findings Recent studies focused on functional side (muscle metabolism and the altered expression of proteins) hypothesize the role of peripheral factors in the maintenance of chronic pain. The results of some studies show the increased concentration of the end products of anaerobic glycolysis and a damage in oxidative metabolism caused by localized hypoxia. In addition, it is present as an insufficient capacity of promoting muscle recovery with inflammation and in metabolic pathway alterations. Unfortunately, these changes are nonspecific and the importance of peripheral factors remains under debate. Summary Morphological and metabolic changes exist in muscle of patients with fibromyalgia but they are not specific and are not sufficient for a definite diagnosis. Nevertheless, the results obtained so far indicate a role of peripheral factors for maintaining the intensity of pain. Therefore, it is desirable to have a better understanding of peripheral muscle alteration that could open up for new therapeutic strategies. [ABSTRACT FROM AUTHOR]

Objective: To describe a second hereditary sensory autonomic neuropathy type VI (HSAN-VI) family harboring 2 novel heterozygous mutations in the dystonin ( DST ) gene and to evaluate their effect on neurons derived from induced pluripotent stem cells (iPSC)., Methods: The family consisted of 3 affected siblings from nonconsanguineous healthy parents. All members underwent clinical and electrophysiologic evaluation and genetic analysis. Two patients underwent quantitative sensory testing (QST), cardiovascular reflexes, dynamic sweat test, and skin biopsy to evaluate somatic and autonomic cutaneous innervation and to get fibroblast cultures for developing iPSC-derived neurons., Results: Onset occurred in the first decade, with painless and progressive mutilating distal ulcerations leading to amputation and joint deformity. Sensation to pain, touch, and vibration was reduced. Autonomic disturbances included hypohidrosis, pupillary abnormalities, and gastrointestinal and sexual dysfunction. Nerve conduction studies showed a severe axonal sensory neuropathy. QST and autonomic functional studies were abnormal. Skin biopsy revealed a lack of sensory and autonomic nerve fibers. Genetic analysis revealed 2 pathogenic mutations in the DST gene affecting exclusively the DST neuronal isoform-a2. Neurons derived from iPSC showed absence or very low levels of DST protein and short and dystrophic neuritis or no projections at all., Conclusions: Unlike the previous HSAN-VI family, our description indicates that DST mutations may be associated with a nonlethal and nonsyndromic phenotype. Neuronal loss affects large and small sensory nerve fibers as well as autonomic ones. Induced-PSC findings suggest that dystonin defect might alter proper development of the peripheral nerves. Dystonin-a2 plays a major role in the HSAN-VI phenotype., (© 2017 American Academy of Neurology.)

Objective: To apply next-generation sequencing (NGS) for the investigation of the genetic basis of undiagnosed muscular dystrophies and myopathies in a very large cohort of patients., Methods: We applied an NGS-based platform named MotorPlex to our diagnostic workflow to test muscle disease genes with a high sensitivity and specificity for small DNA variants. We analyzed 504 undiagnosed patients mostly referred as being affected by limb-girdle muscular dystrophy or congenital myopathy., Results: MotorPlex provided a complete molecular diagnosis in 218 cases (43.3%). A further 160 patients (31.7%) showed as yet unproven candidate variants. Pathogenic variants were found in 47 of 93 genes, and in more than 30% of cases, the phenotype was nonconventional, broadening the spectrum of disease presentation in at least 10 genes., Conclusions: Our large DNA study of patients with undiagnosed myopathy is an example of the ongoing revolution in molecular diagnostics, highlighting the advantages in using NGS as a first-tier approach for heterogeneous genetic conditions., (© 2016 American Academy of Neurology.)