Necklace cytoplasmic bodies in hereditary myopathy with early respiratory failure

Uruha, Akinori; Hayashi, Yukiko; Oya, Yasushi; Mori‐Yoshimura, Madoka; Kanai, Masahiro; Murata, Miho; Kawamura, Mitsuru; Ogata, Katsuhisa; Matsumura, Tsuyoshi; Suzuki, Shigeaki; Takahashi, Yukitoshi; Kondo, Takayuki; Kawarabayashi, Tatsuhiko; Ishii, Yuko; Kokubun, Norito; Yokoi, Sana; Yasuda, Rei; Kira, Jun Ichi; Mitsuhashi, Satomi; Noguchi, S.; Nonaka, Ikuya; Nishino, Ichizo

doi:10.1136/jnnp-2014-309009

Cited by 27 publications

(40 citation statements)

References 24 publications

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“…TTN MFM patients generally develop dyspnea in the early stage of disease, leading to the designation of hereditary myopathy with early respiratory failure (HMERF). The arrangement of cytoplasmic bodies in a necklace fashion is a diagnostic hallmark of TTN MFM . Titin is the largest human protein.…”

Section: Lgmd Subgroupsmentioning

confidence: 99%

Untangling the complexity of limb‐girdle muscular dystrophies

Liewluck

Milone

2018

Muscle and Nerve

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The limb-girdle muscular dystrophies (LGMDs) are a group of genetically heterogeneous, autosomal inherited muscular dystrophies with a childhood to adult onset, manifesting with hip- and shoulder-girdle muscle weakness. When the term LGMD was first conceptualized in 1954, it was thought to be a single entity. Currently, there are 8 autosomal dominant (LGMD1A-1H) and 26 autosomal recessive (LGMD2A-2Z) variants according to the Online Mendelian Inheritance in Man database. In addition, there are other genetically identified muscular dystrophies with an LGMD phenotype not yet classified as LGMD. This highlights the entanglement of LGMDs, which represents an area in continuous expansion. Herein we aim to simplify the complexity of LGMDs by subgrouping them on the basis of the underlying defective protein and impaired function. Muscle Nerve 58: 167-177, 2018.

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Section: Lgmd Subgroupsmentioning

confidence: 99%

Untangling the complexity of limb‐girdle muscular dystrophies

Liewluck

Milone

2018

Muscle and Nerve

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“…HMERF is a hereditary myopathy caused by mutations in the A‐band region of TTN . Since the causative gene was reported in 2012, an increasing number of patients with HMERF have been identified worldwide .…”

Section: Discussionmentioning

confidence: 99%

“…There is no or minimal, if any, weakness in the upper limbs at disease onset. Respiratory insufficiency subsequently appears after a median of six years post‐onset (range: 0 − 16 years) , although respiratory symptoms can be the initial manifestation in 24%−36% of patients . Most patients are ambulant when they need nocturnal ventilation .…”

Section: Discussionmentioning

confidence: 99%

A 31‐Year‐Old Man with Slowly Progressive Limb Muscle Weakness and Respiratory Insufficiency

et al. 2017

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A 31-year-old man, with no family history of neuromuscular diseases, received muscle biopsy for slowly progressive muscle weakness. The first symptom he had was difficulty dorsiflexing his feet at age 20 years, which was followed by gradual development of gait disturbance. At age 27 years, he started using a handrail to climb up stairs. At age 28 years, he developed dysphagia for liquid, in addition to difficulty raising arms, which led him to have aspiration pneumonia later in the same year. At age approximately 30 years, he developed dyspnea on exertion. Arterial blood gas analysis revealed hypoxemia (65 mmHg, at room air) and hypercapnia (82 mmHg), with a vital capacity decreased to 780 mL, leading to the diagnosis of chronic type 2 respiratory failure, and non-invasive ventilation was started. At age 31 years, he was unable to walk without aid and required a wheelchair for long distances. Physical examination revealed moderate muscle weakness and atrophy in an asymmetric limbgirdle distribution, together with marked muscle atrophy in the tibialis anterior muscles and weakness in ankle dorsiflexion with Medical Research Council grade 1. Mild neck muscle weakness was also noted. Serum creatine kinase level was 375 IU/L (normal: <287 IU/L). Electromyography showed myopathic changes. Skeletal muscle CT demonstrated remarkable fat tissue replacement in the semitendinosus muscles ( Figure 1A, arrows) at the thigh level. PATHOLOGYSkeletal muscle pathology from the biceps brachii demonstrated myopathic changes with moderate fiber size variation, mildly disorganized myofibrillar networks, some fibers with cytoplasmic bodies, which were often located in line in subsarcolemmal region of a muscle fiber ( Figure 1B, modified Gomori trichrome stain), and a few fibers with rimmed vacuoles.

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“…In their JNNP paper Uruha et al 1 explore the diagnostic utility of necklace cytoplasmic bodies in patients with hereditary myopathy with early respiratory failure (HMERF). HMERF is a rare autosomal dominant disease characterised by skeletal muscle weakness and respiratory failure as early symptoms, usually presenting in the third or fourth decade of life.…”

mentioning

confidence: 99%

“…Cytoplasmic bodies are abnormal protein deposits observed as red-coloured inclusions on modified Gomori trichrome staining. Muscle tissues from patients with HMERF often show cytoplasmic bodies concentrated within the subsarcolemmal region that form a ‘necklace’-type appearance, which Uruha et al 1 termed ‘necklace cytoplasmic bodies’. In a cohort of 187 patients diagnosed with myofibrillar myopathy, 17 harboured a mutation within exon 343 of TTN .…”

mentioning

confidence: 99%