Infantile Intranuclear Rod Myopathy

Goebel, Hans H.; Piirsoo, Anders; Warlo, Irene; Schofer, O.; Kehr, S.; Gaude, Michael

doi:10.1177/088307389701200104

Cited by 42 publications

(24 citation statements)

References 11 publications

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“…Furthermore, we did not perform an analysis of copy number variations. In intranuclear rod myopathy, which is a congenital nemaline myopathy with more severe disease course, nemaline rods are frequently found inside myonuclei [43]. Until recently, the only known causative gene was ACTA1 [44].…”

Section: Discussionmentioning

confidence: 99%

Sporadic late-onset nemaline myopathy: clinico-pathological characteristics and review of 76 cases

Schnitzler

Schreckenbach²,

Nadaj‐Pakleza

et al. 2017

Orphanet J Rare Dis

132

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BackgroundSporadic late-onset nemaline myopathy (SLONM) is a rare, late-onset muscle disorder, characterized by the presence of nemaline rods in muscle fibers. Phenotypic characterization in a large cohort and a comprehensive overview of SLONM are lacking.MethodsWe studied the clinico-pathological features, treatment and outcome in a large cohort of 76 patients with SLONM, comprising 10 new patients and 66 cases derived from a literature meta-analysis (PubMed, 1966–2016), and compared these with 15 reported HIV-associated nemaline myopathy (HIV-NM) cases. In 6 SLONM patients, we performed a targeted next-generation sequencing (NGS) panel comprising 283 myopathy genes.ResultsSLONM patients had a mean age at onset of 52 years. The predominant phenotype consisted of weakness and atrophy of proximal upper limbs in 84%, of proximal lower limbs in 80% and both in 67%. Other common symptoms included axial weakness in 68%, as well as dyspnea in 55% and dysphagia in 47% of the patients. In 53% a monoclonal gammopathy of unknown significance (MGUS) was detected in serum. The mean percentage of muscle fibers containing rods was 28% (range 1–63%). In 2 cases ultrastructural analysis was necessary to detect the rods. The most successful treatment in SLONM patients (all with MGUS) was autologous peripheral blood stem cell therapy. A targeted NGS gene panel in 6 SLONM patients (without MGUS) did not reveal causative pathogenic variants.In a comparison of SLONM patients with and without MGUS, the former comprised significantly more males, had more rapid disease progression, and more vacuolar changes in muscle fibers. Interestingly, the muscle biopsy of 2 SLONM patients with MGUS revealed intranuclear rods, whereas this feature was not seen in any of the biopsies from patients without paraproteinemia.Compared to the overall SLONM cohort, significantly more HIV-NM patients were male, with a lower age at onset (mean 34 years). In addition, immunosuppression was more frequently applied with more favorable outcome, and muscle biopsies revealed a significantly higher degree of inflammation and necrosis in this cohort. Similar to SLONM, MGUS was present in half of the HIV-NM patients.ConclusionsSLONM presents a challenging, but important differential diagnosis to other neuromuscular diseases of adult onset. Investigations for MGUS and HIV should be performed, as they require distinct but often effective therapeutic approaches. Even though SLONM and HIV-NM show some differences, there exists a large clinico-pathological overlap between the 2 entities.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-017-0640-2) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Sporadic late-onset nemaline myopathy: clinico-pathological characteristics and review of 76 cases

Schnitzler

Schreckenbach²,

Nadaj‐Pakleza

et al. 2017

Orphanet J Rare Dis

132

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“…For example, mutations in α-skeletal actin can result in nemaline myopathy [1,2], intranuclear rod myopathy [3], actin accumulations [4], congenital fibre type disproportion (CFTD) [5], cap disease [6], and zebra body myopathy [7]. …”

Section: Introductionmentioning

confidence: 99%

Approach to the diagnosis of congenital myopathies

North¹,

Wang²,

Clarke³

et al. 2014

Neuromuscular Disorders

263

228

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Over the past decade there have been major advances in defining the genetic basis of the majority of congenital myopathy subtypes. However the relationship between each congenital myopathy, defined on histological grounds, and the genetic cause is complex. Many of the congenital myopathies are due to mutations in more than one gene, and mutations in the same gene can cause different muscle pathologies. The International Standard of Care Committee for Congenital Myopathies performed a literature review and consulted a group of experts in the field to develop a summary of (1) the key features common to all forms of congenital myopathy and (2) the specific features that help to discriminate between the different genetic subtypes. The consensus statement was refined by two rounds of on-line survey, and a three-day workshop. This consensus statement provides guidelines to the physician assessing the infant or child with hypotonia and weakness. We summarise the clinical features that are most suggestive of a congenital myopathy, the major differential diagnoses and the features on clinical examination, investigations, muscle pathology and muscle imaging that are suggestive of a specific genetic diagnosis to assist in prioritisation of genetic testing of known genes. As next generation sequencing becomes increasingly used as a diagnostic tool in clinical practise, these guidelines will assist in determining which sequence variations are likely to be pathogenic.

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“…These exhibit the same crystalline lattice pattern as sarcoplasmic rods, and also contain a-actinin [7]. Although apparently of identical composition, the intranuclear inclusions tend to be larger than typical cytoplasmic rods, with an often polygonal or round shape [7]. In most reported cases with intranuclear rods, inclusions have also been found in their usual location within the sarcoplasm.…”

Section: Discussionmentioning

confidence: 92%

“…However, there have been several reports of rods within the nuclei as well [5^8]. These exhibit the same crystalline lattice pattern as sarcoplasmic rods, and also contain a-actinin [7]. Although apparently of identical composition, the intranuclear inclusions tend to be larger than typical cytoplasmic rods, with an often polygonal or round shape [7].…”

Section: Discussionmentioning

confidence: 97%

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Intranuclear Rod Myopathy, a Rare and Morphologically Striking Variant of Nemaline Rod Myopathy

Weeks

Nixon

Kaimaktchiev

et al. 2003

Ultrastructural Pathology

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A 4-year-old boy with muscle weakness underwent skeletal muscle biopsies. Light microscopy showed distinct eosinophilic inclusions within the majority of muscle cell nuclei, but none in the cytoplasm. Electron microscopy revealed crystalline, round to rod-shaped inclusions in the muscle cell nuclei. The inclusions stained positively for alpha-actinin. Intranuclear inclusions identical to those seen here have been described in rare cases of nemaline rod myopathy, though almost always together with classic intracytoplasmic rods. This case illustrates the importance of electron microscopy in the diagnosis of rare myopathies and in the characterization of cellular inclusions of unknown origin.

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Infantile Intranuclear Rod Myopathy

Cited by 42 publications

References 11 publications

Sporadic late-onset nemaline myopathy: clinico-pathological characteristics and review of 76 cases

Sporadic late-onset nemaline myopathy: clinico-pathological characteristics and review of 76 cases

Approach to the diagnosis of congenital myopathies

Intranuclear Rod Myopathy, a Rare and Morphologically Striking Variant of Nemaline Rod Myopathy

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