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The phenotypes associated with pathogenic variants in the ryanodine receptor 1 gene (RYR1, OMIM# 180901) have greatly expanded over the last few decades as genetic testing for RYR1 variants has become more common. Initially described in association with malignant hyperthermia, pathogenic variants in RYR1 are typically associated with core pathology in muscle biopsies (central core disease or multiminicore disease) and symptomatic myopathies with symptoms ranging from mild weakness to perinatal lethality. We describe a 2-week-old male patient with multiple congenital dysmorphisms, severe perinatal weakness, and subsequent demise, whose histopathology on autopsy was consistent with congenital muscular dystrophy. Immunohistochemical analysis of dystrophy-associated proteins was normal. Rapid exome sequencing revealed a novel heterozygous nonsense variant (p.Trp661Ter) in RYR1, as well as a previously described RYR1 pathogenic variant associated with congenital myopathy (p.Phe4976Leu). This highlights the potential for RYR1 pathogenic variants to produce pathological findings most consistent with congenital muscular dystrophy.

Electromyographic recordings of fibrillation potentials (FPs) and positive sharp waves (PSWs) demonstrate transformation of FP to PSW and vice versa, atypical firing patterns, changes in waveform shape and amplitude, and time‐locked potentials. The etiology of the waveform characteristics of FP and PSW is discussed based on abnormal propagation in a small section of muscle fiber that is “damaged” by the needle. The results of simple computer simulations are described. © 2000 John Wiley & Sons, Inc. Muscle Nerve 23: 888–894, 2000

Electromyographic recordings of fibrillation potentials (FPs) and positive sharp waves (PSWs) demonstrate transformation of FP to PSW and vice versa, atypical firing patterns, changes in waveform shape and amplitude, and time-locked potentials. The etiology of the waveform characteristics of FP and PSW is discussed based on abnormal propagation in a small section of muscle fiber that is “damaged” by the needle. The results of simple computer simulations are described. © 2000 John Wiley & Sons, Inc. Muscle Nerve 23: 888–894, 2000

Sporadic inclusion body myositis (S‐IBM) is a progressive, acquired disease of unknown etiology. Prior studies have suggested neurogenic involvement based on electrophysiologic data, although the biopsy is compatible with a myopathic process. Quantitative electrophysiologic studies were performed in the biceps brachii of 17 subjects with biopsy‐proven S‐IBM. Quantitative motor unit action potential (MUAP) analysis was compatible with myopathy in 16 subjects, with the remaining subject being within normal limits. Quantitative interference pattern was myopathic in all 13 subjects studied. Macro‐EMG MUAP amplitude was reduced in 3 of 17 studies; the remainder were within normal range, and none was increased as would be expected in neurogenic disease. Fiber density was normal to borderline increased in all subjects. Possible reasons for encountering neurogenic‐appearing MUAPs may include choice of muscle studies, because some patients have co‐existing polyneuropathy and large‐amplitude MUAPs from hypertrophied muscle fibers. The data from this study indicate that S‐IBM is a myopathic process. © 1999 John Wiley & Sons, Inc. Muscle Nerve 22: 480–487, 1999.

Sporadic inclusion body myositis (S-IBM) is a progressive, acquired disease of unknown etiology. Prior studies have suggested neurogenic involvement based on electrophysiologic data, although the biopsy is compatible with a myopathic process. Quantitative electrophysiologic studies were performed in the biceps brachii of 17 subjects with biopsy-proven S-IBM. Quantitative motor unit action potential (MUAP) analysis was compatible with myopathy in 16 subjects, with the remaining subject being within normal limits. Quantitative interference pattern was myopathic in all 13 subjects studied. Macro-EMG MUAP amplitude was reduced in 3 of 17 studies; the remainder were within normal range, and none was increased as would be expected in neurogenic disease. Fiber density was normal to borderline increased in all subjects. Possible reasons for encountering neurogenic-appearing MUAPs may include choice of muscle studies, because some patients have co-existing polyneuropathy and large-amplitude MUAPs from hypertrophied muscle fibers. The data from this study indicate that S-IBM is a myopathic process. © 1999 John Wiley & Sons, Inc. Muscle Nerve 22: 480–487, 1999.

• Six cases of a comparatively rare motor neuron disease are described. Essential features of this syndrome include (1) X-linked inheritance; (2) adult onset in the fourth to fifth decades; (3) slow progression; (4) predominant proximal and bulbar muscle involvement; and (5) absence of sensory or pyramidal tract signs. The previously reported finding of gynecomastia was absent, whereas longitudinal midline furrowing of the tongue was present in only one case. Electromyography in five patients revealed neurogenic changes. Muscle biopsies in two patients showed fiber type grouping with type I fiber predominance. The coexistence of this form of motor neuron disease and diabetes mellitus is prominent in family 2. It is important to recognize that these patients have a chronic, slowly progressive illness. The prognosis for longevity is good, although severe disability is inevitable. Management includes reassurance, supportive therapy, genetic counseling, and periodic testing for diabetes.

• Seven unrelated women were manifesting carriers of Duchenne muscular dystrophy. A manifesting carrier of Duchenne muscular dystrophyis defined as a female with a history of Duchenne muscular dystrophy in her pedigree who has symptomatic weakness. All were characterized by slowly progressive weakness that began in the second or third decade of life. Asymmetric weakness was present in only three of the seven patients. Serum creatine kinase values were elevated in all patients and none had an electrocardiogram indicating ventricular hypertrophy. The electromyogram and muscle biopsy specimens were reported as myopathic in all patients studied. In the absence of a male relative with Duchenne muscular dystrophy, clinical distinction from cases of autosomal recessive limb girdle muscular dystrophy may not be possible. The development of new techniques in molecular genetics should allow precise identification of manifesting carriers of Duchenne muscular dystrophy in the near future.

No abstract.

It is not possible to discuss academic neurology from the mid-20th to the early 21st century and not mention one of its most influential contributors, Professor Irena Hausmanowa-Petrusewicz. She died at her home and in the city with which she will always be associated, Warsaw, Poland, on July 7, 2015, at the age of 97. Professor Hausmanowa-Petrusewicz's parents came from Lvov, Poland, and their careers presaged their daughter's career. Her father was a literary critic and her mother was a Swiss-educated dermatologist who was one of the first female physicians in Poland.

IN REPLY. —Limb-girdle dystrophy is a rubric that is considered "obsolete" by some authors1 and may be best considered a syndrome. We were unable to find specific discussions on autosomal dominant limb-girdle dystrophy in the citations1,2 offered by Boylan. We agree that one cannot clinically differentiate the autosomal dominant from the autosomal recessive forms.3 Without adequate family history and pedigree analysis, an autosomal dominant pattern of inheritance, although quite rare,3 obviously cannot be excluded. If an autosomal dominant pattern is established, however, one can virtually eliminate the possibility of a Duchenne dystrophy manifesting carrier since there cannot be male-to-male transmission of Duchenne dystrophy. This explains the focus on autosomal recessive and sporadic limb-girdle dystrophy as the major differential diagnosis for Duchenne dystrophy manifesting carrier in our article.4 Perhaps we should simplify this issue and reiterate that females with a limb-girdle syndrome and no family history