Genetic Patterns of Selected Muscular Dystrophies in the Muscular Dystrophy Surveillance, Tracking, and Research Network.

Background and Objectives: To report the genetic etiologies of Emery-Dreifuss muscular dystrophy (EDMD), limb-girdle muscular dystrophy (LGMD), congenital muscular dystrophy (CMD), and distal muscular dystrophy (DD) in 6 geographically defined areas of the United States. Methods: This was a cross-sectional, population-based study in which we studied the genes and variants associated with muscular dystrophy in individuals who were diagnosed with and received care for EDMD, LGMD, CMD, and DD from January 1, 2008, through December 31, 2016, in the 6 areas of the United States covered by the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet). Variants of unknown significance (VUSs) from the original genetic test reports were reanalyzed for changes in interpretation. Results: Among 243 individuals with definite or probable muscular dystrophy, LGMD was the most common diagnosis (138 cases), followed by CMD (62 cases), DD (22 cases), and EDMD (21 cases). There was a higher proportion of male individuals compared with female individuals, which persisted after excluding X-linked genes (EMD) and autosomal genes reported to have skewed gender ratios (ANO5, CAV3, and LMNA). The most common associated genes were FKRP, CAPN3, ANO5, and DYSF. Reanalysis yielded more definitive variant interpretations for 60 of 144 VUSs, with a mean interval between the original clinical genetic test of 8.11 years for all 144 VUSs and 8.62 years for the 60 reclassified variants. Ten individuals were found to have monoallelic pathogenic variants in genes known to be primarily recessive. Discussion: This study is distinct for being an examination of 4 types of muscular dystrophies in selected geographic areas of the United States. The striking proportion of resolved VUSs demonstrates the value of periodic re-examinations of these variants. Such re-examinations will resolve some genetic diagnostic ambiguities before initiating repeat testing or more invasive diagnostic procedures such as muscle biopsy. The presence of monoallelic pathogenic variants in recessive genes in our cohort indicates that some individuals with muscular dystrophy continue to face incomplete genetic diagnoses; further refinements in genetic knowledge and diagnostic approaches will optimize diagnostic information for these individuals.

The Slipping Slipper Sign: A Poor Man's Test for Severe Diabetic Peripheral Neuropathy.

BACKGROUND: Neuropathic feet are at very high risk for infection and amputation. The slipping slipper sign (SSS) is elicited by a simple questionnaire test reported to detect the presence of severe diabetic peripheral neuropathy. This test can be administered by non-medical staff. In this study, subjects with and without the SSS were evaluated by nerve conduction studies (NCS) and ultrasound measurements of the right sural nerve diameters as well as with traditional scoring systems for peripheral and autonomic neuropathy. OBJECTIVE: To demonstrate that the Slipping Slipper Sign can be used as an index of severe diabetic peripheral neuropathyMethod:This was a prospective cross sectional study in which 74 patients with diabetes (38 positive and 36 negative for SSS) underwent ultrasonography and NCS of the right sural nerve by an examiner blinded to SSS status. Findings were evaluated against demography, clinical history, anthropometry as well as traditional clinical and autonomic neuropathic scores. RESULTS: Patients without the SSS [median (IQR) = 10.0 years (4.0-20.3)] had a significantly shorter duration of diabetes compared with those with the SSS [median (IQR) = 15.0 years (8.5-25.0)], p = 0.028. The frequencies of retinopathy (36.8% vs 2.8%, p <  0.05) and cerebrovascular accidents (18.4% vs 13.9 %, p <  0.05) were higher among those with SSS compared with those without. Differences in nerve conduction characteristics were markedly significant. The amplitude of the sural sensory nerve action potential (SNAP) was ([median (IQR)] 0 microvolts vs 4.0 microvolts (0.0-10.8) p <  0.002) between those with and without SSS, respectively whilst none of patients with SSS had a recordable SNAP vs 78% without a SSS. Similarly, maximal thickness of the right sural nerve at the ankle 3.0 mm (2.3-3.4) vs 3.5 mm (3.0-3.9), and leg 3.4 mm (2.7-3.8) vs 3.9 mm (3.3-4.2) was reduced, p <  0.01 in patients with the SSS compared with those with a negative SSS. CONCLUSION: The SSS identifies feet with objective neurophysiological and imaging characteristics of severe neuropathy.

Neurologic complications of sit-ups associated with the Valsalva maneuver: 2 case reports.

We present 2 cases of potentially catastrophic neurologic consequences occurring in healthy individuals engaged in sit-up exercises. Two young healthy men were engaged in sit-ups when one developed a stroke and the other developed a spinal epidural hematoma. The Valsalva maneuver involved in the sit-up exercise can produce supraphysiologic increases in blood pressure, which can lead to vascular injury and serious neurologic consequences. Proper breathing should be encouraged and patients with known predisposing factors should avoid such exercises. Prompt recognition of neurologic signs and symptoms during exercise can be life saving. This is the first report of the neurologic complications of sit-ups.