Desmin body myofibrillar myopathy …

Jean K Mah MD

Developmental Malformations

Updated 07.06.2024
Released 11.30.1996
Expires For CME 07.06.2027

Desmin body myofibrillar myopathy

Author: Jean K Mah MD

See Contributor Disclosures

Editor: Harvey B Sarnat MD FRCPC MS

Desmin body myofibrillar myopathy

In This Article

Quick Link

Introduction

Overview

Myofibrillar myopathies refer to a heterogeneous group of genetic disorders associated with disintegration of myofibrils and accumulation of Z-disc related proteins, with variable age of onset and disease progression. Patients present with lower limb muscle weakness, which slowly spreads to involve the upper limbs, truncal, neck-flexor, facial, bulbar, and respiratory muscles. Distribution of the weakness may be distal or both proximal and distal. Skeletal myopathy may be combined with or preceded by cardiomyopathy, conduction blocks, and arrhythmias that can result in sudden death. Respiratory muscle weakness can also be a major complication in some patients. In this updated article, the author highlights advances in the diagnosis and management of myofibrillar myopathies.

Key points

	• Myofibrillar myopathies are a subgroup of hereditary protein aggregate myopathies.
	• Muscle biopsy reveals characteristic amorphous or granular material, with focal areas of myofibrillar disintegration, reduced oxidative enzyme activity, and vacuolar changes.
	• The clinical phenotype is highly variable; most commonly it presents as a distal myopathy involving the hands and feet, with progressive muscle weakness, respiratory dysfunction, and cardiomyopathy.
	• Treatment remains primarily supportive; those with significant cardiac complications may require pacemaker implantation or cardiac transplant.

Historical note and terminology

Myofibrillar myopathies refer to a heterogeneous group of rare inherited primary chronic noninflammatory myopathies characterized by abnormal accumulation of cytoplasmic inclusion bodies and myofibrillar disarray in skeletal or cardiac muscles (45; 06; 39). The disease was originally described more than 30 years ago based on common muscle histopathological features (44). The onset usually occurs in adult life (between the second and fourth decade) but may be congenital or present in early childhood. A combination of distal and proximal weakness, cardiomyopathy, peripheral neuropathy, and autosomal dominant inheritance should suggest this disorder (84). However, sporadic, autosomal recessive, or X-linked inheritance have also been described (38; 114).

The first description of cytoplasmic body as a structural anomaly of the Z-disc was in 1969 (78). Cytoplasmic bodies occur in a number of unrelated neuromuscular disorders, but their relationship to desmin-related neuromuscular diseases was only recognized in the 1980s (33; 130; 92).

Sporadic cases of adult-onset myopathy with spheroid inclusions, cytoplasmic bodies, and myofibrillar aggregates were initially reported in the 1970s (85; 65; 61). An autosomal dominantly inherited form of proximal myopathy was also described with spheroid bodies (47), granulofilamentous aggregates (35; 19), and myofibrillar inclusions (19). Intermediate filaments were identified in association with sarcoplasmic bodies in families with a severe progressive late-onset autosomal dominant distal myopathy (33), an adult-onset limb-girdle myopathy (32), and a distal myopathy (57). Subsequent cases had cardiomyopathy with large proteinaceous inclusions identified in the cardiac muscle consisting of intermediate filaments that were immunofluorescent desmin-positive (100; 130). Desmin body myofibrillar myopathy was also associated with a congenital form of myopathy with or without cardiomyopathy (48; 145). The cardiomyopathy could precede the myopathy (10; 49).

Clinical manifestations

Presentation and course

In a typical presentation, the disease is characterized by bilateral weakness in the distal leg muscles spreading proximally, or in proximal muscles spreading distally and eventually leading to wheelchair dependence. There can also be slowly progressive proximal muscle weakness, significant distal and proximal weakness, predominant distal weakness, or generalized muscle weakness with dysphonia and dysphagia (35; 47; 33). The cranial nerves are usually spared. Subgroups are characterized according to clinical presentation (04).

Cardiac involvement is frequent. The cardiomyopathy may be hypertrophic (35; 100), congestive (145; 49), or restrictive (109); it may precede the myopathy by a number of years (134; 60). There are also reports of patients with cardiomyopathy and clinically silent or only mild skeletal muscle disease (100; 12; 127). The cardiomyopathy is associated with frequent cardiac arrhythmias and either ventricular conduction blocks or atrioventricular conduction blocks requiring a pacemaker, often with progression to congestive cardiac failure and premature demise (100; 55; 57; 60). Neither the severity of skeletal muscle weakness nor the type of DES mutations was found to correlate significantly with the extent of cardiac involvement (140).

Respiratory muscle involvement is common. In adult-onset cases, respiratory muscle weakness and acute respiratory incapacity may be the initial presenting features (61; 32; 57; 11). Respiratory failure also occurs in congenital cases (07).

A peripheral neuropathy can be present. Both a sensorimotor polyneuropathy and a motor or sensory predominant neuropathy have been described (109; 84; 59; 20; 23). The Achilles reflexes may initially be absent, followed by loss of knee reflexes and preservation of arm reflexes until late in the disease (57).

Rarely, homozygous variants in desmin gene (recessive desminopathies) may present as a congenital myasthenic syndrome with ocular, bulbar, and limb-girdle muscle weakness, confirmed by positive electrodecremental response to repetitive nerve stimulation and partial responsiveness to treatment with pyridostigmine and salbutamol (99).

Skeletal abnormalities, such as thoracispinal kyphoscoliosis (145; 109; 83) and lumbar lordosis, may occur (55; 41). Cranial acromegaly with large frontal sinus, high-arched palate (145; 41), micrognathia, and cleft palate has been described (65). Bilateral pes cavus and camptocormia can occur (109; 55; 105). Extramuscular manifestations including mental retardation and late onset cerebellar ataxia have been reported as well (83; 102).

Most cases of myofibrillar myopathies present after the first decade or later in life. Early onset disease with homozygous alpha-B-crystallin (CRYAB) mutations were described in Canadian aboriginal infants of Cree ancestry with hypertonia, muscle rigidity, and early respiratory insufficiency shortly after birth (70; 24). Extensive fibrosis and absence of alpha-B-crystallin immunoreactivity were important diagnostic clues for this entity (24; 81; 76). Other congenital forms of myofibrillar myopathies may be benign (41), severe (07), or associated with progressive muscle weakness (36; 41; 68).

Prognosis and complications

Myofibrillar myopathy may be slowly progressive, remain relatively static, or become severe, with some patients becoming wheelchair-bound within 10 years (33). The prognosis also depends on the presence or absence of an accompanying cardiomyopathy with or without cardiorespiratory failure. Age of disease onset in patients with autosomal dominant disease is between 14 and 48 years of age, whereas patients with recessive mutations may present during childhood or adolescence. Disease progression may be faster in patients with autosomal recessive DES mutations and cardiomyopathy (50).

Clinical vignette

A 13-year-old girl was referred for initial assessment. Her past medical history was unremarkable apart from a recent history of intermittent dizziness and shortness of breath during intense physical activity. She denied any chest pain, palpitations, syncope, seizures, weakness, or numbness. Her exam was normal apart from mild distal muscle weakness and atrophy in her hands and feet, plus a mild stocking and glove distribution of reduced pinprick, temperature, vibration, and light touch up to her wrists and ankles in a symmetrical fashion.

Her family history was significant for cardiomyopathy in her father; he required a cardiac transplantation at 20 years of age. He noticed a gradual decline in strength during his early 30s, initially with distal lower extremities weakness, followed by gradual progression to involve his proximal lower and then upper limbs. His recent quadriceps biopsy revealed a myofibrillary myopathy with increased variation in fiber size, occasional atrophic myofibers, and multiple hyaline inclusions that reacted positively to desmin immunostaining.

Initial laboratory tests including serum creatine kinase, electrolytes, glucose, complete blood count, serum B12, and thyroid function were normal. Her electrocardiogram showed a first-degree atrioventricular block and a right bundle branch block. An exercise stress test showed a normal heart rate and blood pressure response, but the test was terminated early due to subjective sensation of chest tightness. A 24-hour Holter monitoring showed no other significant rhythm disturbance. Her echocardiogram, cardiac MRI, nerve conduction study, and pulmonary function tests were within normal limits. Molecular genetic testing confirmed a pathologic DES gene mutation in both the father and daughter. She had implantation of a MRI-compatible VVIR (demand ventricular pacing with physiologic response to exercise) pacemaker for persistent trifascicular conduction block. She remained otherwise asymptomatic, with stable cardiac, pulmonary, and neurologic assessments a year later.

Biological basis

Etiology and pathogenesis

Myofibrillar myopathies are considered a subgroup of protein aggregate myopathies (45; 06; 16). Myofibrillar myopathies (MFM) are characterized by a broad spectrum of pathologic changes found in muscle, including focal disintegration of myofibrils, mitochondrial dysfunction, and accumulation of multiple sarcoplasmic proteins including desmin (22; 84; 117; 118; 118). Desmin was initially identified as a key molecule associated with a diverse group of disorders. Molecular studies have demonstrated mutations in desmin and alpha-B-crystallin genes in patients with a clinical phenotype of desminopathy. Other proteins besides desmin were subsequently found to accumulate in the abnormal myofibrils.

Approximately half of the myofibrillar myopathies are caused by mutations in genes encoding sarcomeric and extra-sarcomeric proteins, including desmin (51; 82; 21), alpha-B-crystallin (136; 120), myotilin (121), LIM-domain-binding protein 3 (LDB3, also known as ZASP) (122), filamin C (139; 108; 133; 72), Bcl2-associated athanogene 3 (Bag3) (125; 59), and DnaJ homolog subfamily B member 6 (DNAJB6) (143; 111). In addition, mutations involving four and a half LIM domain 1 (FHL1) and titin (TTN) were found in a subgroup of patients with myofibrillar myopathies, reducing body myopathy, or hereditary myopathy with early respiratory failure (115; 90; 38; 98). Defects in the genes encoding human plectin (PLEC), alpha-actin (ACTA1), small heat shock protein 22 (HSPB8), lamin A/C (LMNA), kyphoscoliosis peptidase (KY), pyridine nucleotide-disulfide oxidoreductase domain-containing protein 1 (PYROXDI), sequestosome 1 (SQSTMI) in combination with a modifying variant in cytotoxic granule-associated RNA-bind protein (TIA1), and tripartite motif-containing protein 32 (TRIM32) can also give rise to myofibrillar aggregations with vacuolar changes (66; 66; 89; 26; 88; 93; 86). Many of the above genes are associated with other types of myopathies.

Myopathic manifestations caused by desmin (DES) or alpha-B-crystallin (CRYAB) mutations are identical but are termed “desminopathy” when desmin is involved and “alpha-B-crystallinopathy” when alpha-B-crystallin is involved (136; 21; 120; 117; 118; 77). Similarly, mutations involving myotilin (MYOT), Z-band alternately spliced PDZ motif-containing protein (ZASP), filamin C (FLNC), or bcl-2-associated athanogene 3 (Bag3) result in myotilinopathy, zaspopathy, filaminopathy, or Bag3opathy, respectively (121; 122; 139; 125; 59; 108; 133; 69).

Muscle biopsy changes in myofibrillar myopathy are those of focal dissolution of myofibrils followed by accumulation of the products of myofibrillar degradation. Each process is associated with an anomaly of the Z-disc, indicating that this plays a role in the pathogenesis of the disease (84).

Subsarcolemmal desmin-positive inclusions (photomicrograph)

An immunoperoxidase stain performed on a longitudinal section of skeletal muscle showing subsarcolemmal desmin-positive inclusions. (x128) (Contributed by Dr. Victoria Anne Fabian.)
Subsarcolemmal filamentous cytoplasmic body (electron micrograph)

Electron micrograph of skeletal muscle showing a subsarcolemmal filamentous cytoplasmic body. (x2100) (Contributed by Dr. Victoria Anne Fabian.)

The main muscle intermediate filament of desmin, formally called "skeletin," is a 53-kd protein and a class 3 muscle-specific intermediate filament measuring 8 to 10 nm in diameter and occurring in skeletal, cardiac, and smooth muscle. Desmin is encoded by a single copy gene (DES), and the human desmin gene is localized to chromosome 2q35 (104; 138). It encompasses nine exons and codes for 476 amino acids. In mature skeletal muscle, desmin filaments encircle and interlink the myofibrils at the level of the Z-disc and connect to the plasma membrane and nuclear lamina, thus, aligning the myofibrils. Desmin is enhanced at the myotendinous and neuromuscular junctions (44). Desmin occurs in high concentration in developing striated myofibers, especially fetal myotubes, and then diminishes in mature muscle where it functions in maintaining the alignment of Z-bands of adjacent myofibrils (112; 113).

Earlier research suggests that desmin plays a role in the functional and spatial relationship between the nucleus and plasma membrane, linked to the nuclear intermediate filament laminin B (44). In the heart, desmin is increased at the intercalated discs and in the Purkinje fibers (103). Like other intermediate filament proteins, desmin is composed of three major structural domains (56). N-terminal end is a nonconserved non-alpha-helical head domain; middle is a conserved alpha-helical coiled-coil rod domain that contains three linker regions; and C-terminal end is a nonconserved tail domain (43). Partial knockdown of the desmin genes resulted in smaller organisms with diminished active tension and force generation as well as increased vulnerability to acute stretch injury (74; 62).

DES mutations cause loss of function of both desmin and its binding partners, as well as toxic accumulation of aggregates containing misfolded desmin and debris from other ectopically expressed proteins within the myofiber (13; 64; 01). Mutant desmin also interacts with other cytoskeletal proteins. The pathologic process starts with disintegration of Z-disc, which is the functionally important site for tension transmission between the sarcomeres. The amount of desmin in affected muscle fibers of desminopathy patients increases over time (03). In cultured satellite cells taken from a patient with p.Leu345Pro mutation in the DES gene, desmin created a fully normal network in the early passages; however, in further passages an increasing number of cells showed abnormal accumulation of desmin-positive material in the form of perinuclear, spot-like, or subsarcolemmal pattern (14). Animal models and experiments in desmin knockout mice suggest that desmin is essential for the structural integrity, adhesion, and migration of muscle cells (95; 53). Mutated desmin led to impaired myocyte structure and function (144; 27; 42). Mitochondrial abnormalities also contribute to the development of cardiomyopathy in desmin-related myopathies (58).

Alpha-B-crystallin is a ubiquitous small heat shock protein that has multiple cellular functions, including chaperone-like antiaggregation properties. It normally stabilizes proteins including desmin and prevents their irreversible aggregation (29); one study suggests that alpha-B-crystallin may function as a sensor for proper assembly of intermediate filaments (126). It is found in the lens, skeletal, and cardiac muscle, and to a lesser extent in the skin, brain, and kidney. The human alpha-B-crystallin gene (CRYAB) was first mapped to the 26-cM interval in chromosome 11q21-23, a region containing the CRYAB gene, in a large French pedigree (137; 136). Hyperphosphorylation of alpha-B-crystallin is postulated to be responsible for the deleterious change in various cellular processes (02). Expression of mutant alpha-B crystallin leads to formation of abnormal aggregates that contain both desmin and alpha-B-crystallin (24). Aggregation of amyloid-like material has been described as a typical feature of many human cardiomyopathies, especially those caused by CRYAB mutations (110).

Some studies suggest an important role of autophagy in protection against alpha-B-crystallin or desmin-related myopathies (141). In both mice and in vitro studies, p62 mRNA and protein expression were significantly upregulated in cardiomyocytes by transgenic overexpression of mutant desmin or alpha-B-crystallin (146). The p62 upregulation in mouse proteinopathic hearts promoted aggresome formation and autophagy activation (146).

Accumulation of misfolded proteins is a common pathological pattern in all myofibrillar myopathies (107; 143). The effect of different disease-associated mutations at the molecular level was evaluated by confocal single-particle fluorescence spectroscopy (73). De novo aggregation properties of desmin in vitro and divergent assembly patterns for three different desmin missense mutations were detected. R350P-desmin showed a strong inhibition of assembly formation with a reduced level of tetramers and an increase in dimers in native cell extracts. It interacted with wild-type protein resulting in a dominant negative effect on desmin assembly. E413K-desmin formed hyperstable tetramers whereas R454W-desmin had subtle effects at the dimer and tetramer levels. The study of cultured human myoblasts suggests that increased stiffness as expressed by desmin mutation may contribute to the progressive muscle damage due to excessive mechanical stress (08). Some studies suggest that desmin plays a key role in the rheological properties of the cytoplasm in myoblasts (34; 17). In a study, pretreatment with N-acetyl-L-cysteine (NAC) decreased stress-induced protein aggregation in desmin mutant cell lines; however, NAC did not reduce protein aggregation in AAV-injected mouse models of desminopathies (25).

The location of DES mutations can exert a significant influence on the clinical phenotype (50; 135). Pathologic DES variants located in the 1B segment of the alpha-helical rod domain and the tail domain were more likely to present with early-onset severe cardiomyopathy compared to patients with variants in other segments (129). Myopathy, cardiomyopathy, smooth muscle myopathy, neuropathy, respiratory dysfunction, facial paralysis, or cataracts may be present in some desminopathy patients and may be absent in others. There was a tendency for the age of onset to be 4 to 10 years earlier, and disease progression to be faster, in patients with cardiomyopathy or autosomal recessive disease (50; 91). Recessive desmin mutations with complete loss of function were found to be associated with infantile-onset generalized weakness, cardiomyopathy, as well as a congenital myasthenic syndrome in two children attributed to impaired neuromuscular endplates formation, in addition to the myopathy (31).

Diagnostic workup

As shown in the case illustration, the recommended investigations in patients with suspected myofibrillar myopathies include the following (50; 54):

	(1) Electrophysiological investigations, including nerve conduction studies and EMG examination, to exclude neurogenic causes of weakness, such as motor neuron disease and peripheral neuropathy.
	(2) ECG, to identify arrhythmias and cardiac conduction defects.
	(3) Holter monitoring, especially if symptoms suggest an intermittent arrhythmia.
	(4) Echocardiography to detect and diagnose the type of cardiomyopathy, even in patients with no cardiac symptoms.
	(5) Cardiac MRI and MR delayed enhancement imaging if available, to detect subtle myocardial changes or early myocardial fibrosis.
	(6) Respiratory function tests, even in patients with no respiratory symptoms.
	(7) Muscle imaging studies and/or muscle biopsy, to differentiate from other myopathies.
	(8) Genetic testing (including whole exome sequencing), which is essential in establishing an accurate diagnosis and to provide reliable genetic counseling.

Cardiac MRI is superior to conventional echocardiography to identify patients at risk of cardiovascular complications (131; 18). Skeletal muscle MRI can also help confirm the patterns of muscle involvement in myofibrillar myopathies (87), with early involvement of the semitendinosus, sartorius, and gracilis in DES-related myopathies (63).

Electromyogram usually shows a myopathic pattern in the majority of the patients with myofibrillar myopathies; a minority of patients showed mixed neurogenic and myopathic features with myotonic discharges (47; 61; 84). Nerve conduction studies may be normal or show reduced conduction velocities and decreased motor and sensory amplitudes (109; 84). The serum creatine kinase level is usually normal or mildly elevated (less than 7-fold above the upper normal limit).

A muscle biopsy is required to make the diagnosis. The histology usually shows a myopathy. The main features are eosinophilic inclusions of amorphous, granular, or hyaline material in a subsarcolemmal distribution or throughout the sarcoplasm, which on the modified Gomori trichrome stain appear a blue-red-purple color. The NADH stain shows reduced oxidative enzyme activity corresponding to the abnormal hyaline structures. These structures have been termed "inclusion bodies" (85), "spheroid bodies" (47), "Mallory bodies" (40), and "vermiform inclusions" (10). They occur in normal, atrophic, and hypertrophic fibers, mainly in type 1 fibers but also in type 2 fibers (11). There is a variation in fiber size, with atrophy ranging from 6 to 25 µm and hypertrophy from 80 to 150 µm. Inflammatory infiltrates are usually absent. However, focal necrotic fibers with macrophages (10; 55; 57; 84) and regenerating fibers have been reported (84). Desmin is diffusely expressed in regenerating fibers (112). Other features include type 1 fiber predominance, fiber splitting, fibrosis, prominent internal nuclei, and lakes of para-aminosalicylic acid-positive material (84). There are also several vacuoles showing acid phosphatase positivity (10; 84).

Both immunofluorescence and immunoperoxidase staining have demonstrated the association of the granulofilamentous inclusions with desmin accumulation. A large number of proteins, which fall into different categories, have been found overexpressed (22). These proteins include cytoskeletal proteins such as dystrophin (49; 55; 15; 22) and vimentin (55), myofibril-associated proteins such as alpha-actin and actin (10; 32; 116), and proteins seen in relation to amyloid formation such as gelsolin, beta-A4 protein, and the beta-A4 amyloid precursor protein (22). Other proteins include ubiquitin (10; 134), alpha-B-crystallin (49), and antichymotrypsin, a marker of histiocytes (22). Accumulation of RNA polymerase II-associated proteins (RPAPS) was found in the cytoplasm of muscle fibers in familial and sporadic cases of myofibrillar myopathies; RPAP2 immunostaining may be a useful tool to identify abnormal protein aggregation (52). As well, proteomic analysis of the ratio and order of different proteins may help in the differential diagnosis of protein aggregate myopathies (79).

The ultrastructural patterns of the inclusion bodies are heterogeneous. The commonest inclusion is granulofilamentous, segregated into filamentous and electron-dense, finely granular components in various arrangements. The increased use of laser microdissection has permitted quantitative proteomic analysis and novel understanding of the pathogenesis of desminopathy (37; 67). Foci of myofibrillar disruption contain small deposits of irregularly shaped Z-disc material and accumulations of degraded myofibrillar components (84). The filaments described differ and include short fine filaments 6 to 8 nm in diameter representing fragmented actin. The filaments in spheroid bodies range in size from 12 to 15 nm (47). Although intermediate filaments 7 to 10 nm in diameter occur in association with the granular masses (33; 100; 92; 116), they are not usually present in desmin body myofibrillar myopathy. Membrane-bound vacuoles contain degenerating membranous organelles and myeloid structures, and the surrounding myofiber may show abnormal sarcotubular systems, scattered glycogen granules, and mitochondria.

The other inclusions seen are the classic cytoplasmic body (85; 61; 92; 116) and filamentous bodies without electron-dense material (100). Immunogold labeling has demonstrated different localizations of desmin positivity involving the intermediate filaments, the filamentous component (96), or the granulo-amorphous material (11). Desmin, alpha-B-crystallin, and dystrophin occur in the granulofilamentous inclusions (49). The filamentous component is also actin positive (11).

In summary, muscle histology reveals characteristic amorphous or granular material in a variable proportion of the muscle fibers with Gomori trichrome staining; sharply circumscribed decreases of oxidative enzyme activity in many abnormal fiber regions; small vacuoles in a variable number of fibers and abnormal ectopic expression of desmin, alpha-B-crystallin, dystrophin, and other proteins in immunocytochemical studies (50).

Next generation sequencing is essential to identify the disease-causing mutations (101).

References

01: Agnetti G, Herrmann H, Cohen S. New roles for desmin in the maintenance of muscle homeostasis. FEBS J 2021;289(10):2755-70. PMID 33825342
02: Bakthisaran R, Akula KK, Tangirala R, Rao ChM. Phosphorylation of αB-crystallin: Role in stress, aging and patho-physiological conditions. Biochim Biophys Acta 2016;1860(1 Pt B):167-82. PMID 26415747
03: Bar H, Fischer D, Goudeau B, et al. Pathogenic effects of a novel heterozygous R350P desmin mutation on the assembly of desmin intermediate filaments in vivo and in vitro. Hum Mol Genet 2005;14(10):1251-60. PMID 15800015
04: Barohn RJ, Amato JJ, Griggs RC. Overview of distal myopathies: from the clinical to the molecular. Neuromusc Disord 1998;8:308-16. PMID 9673984
05: Batonnet-Pichon S, Behin A, Cabet E, Delort F, Vicart P, Lilienbaum A. Myofibrillar myopathies: new perspectives from animal models to potential therapeutic approaches. J Neuromuscul Dis 2017;4(1):1-15. PMID 28269794
06: Béhin A, Salort-Campana E, Wahbi K, et al. Myofibrillar myopathies: state of the art, present and future challenges. Rev Neurol (Paris) 2015;171(10):715-29. PMID 26342832
07: Bertini E, Ricci E, Boldrini R, et al. Involvement of respiratory muscles in cytoplasmic body myopathy: a pathological study. Brain Dev 1990;12(6):798-806. PMID 2092592
08: Bonakdar N, Luczak J, Lautscham L, et al. Biomechanical characterization of a desminopathy in primary human myoblasts. Biochem Biophys Res Commun 2012;419(4):703-7. PMID 22386993
09: Cabet E, Batonnet-Pichon S, Delort F, Gausserès B, Vicart P, Lilienbaum A. Antioxidant treatment and induction of autophagy cooperate to reduce desmin aggregation in a cellular model of desminopathy. PLoS ONE 2015;10(9):e0137009. PMID 26333167
10: Calderon A, Becker LE, Murphy EG. Subsarcolemmal vermiform deposits in skeletal muscle, associated with familial cardiomyopathy: report of two cases of a new entity. Pediatr Neurosci 1987;13:108-12. PMID 3438215
11: Cameron CH, Mirakhur M, Allen IV. Desmin myopathy with cardiomyopathy. Acta Neuropathol 1995;89:560-6. PMID 7676812
12: Cao L, Hong D, Zhu M, Li X, Wan H, Hong K. A novel heterozygous deletion-insertion mutation in the desmin gene causes complete atrioventricular block and mild myopathy. Clin Neuropathol 2013;32(1):9-15. PMID 23036309
13: Capetanaki Y, Papathanasiou S, Diokmetzidou A, Vatsellas G, Tsikitis M. Desmin related disease: a matter of cell survival failure. Curr Opin Cell Biol 2015;32:113-20. PMID 25680090
14: Carlsson L, Fischer C, Sjoberg G, Robson RM, Sejersen T, Thornell LE. Cytoskeletal derangements in hereditary myopathy with a desmin L345P mutation. Acta Neuropathol 2002;104(5):493-504. PMID 12410397
15: Caron A, Viader F, Lechevalier B, Chapon F. Cytoplasmic body myopathy: familial cases with accumulation of desmin and dystrophin. An immunohistochemical, immunoelectron microscopic biochemical study. Acta Neuropathol 1995;90:150-7. PMID 7484090
16: Carvalho AAS, Lacene E, Brochier G, et al. Genetic mutations and demographic, clinical, and morphological aspects of myofibrillar myopathy in a French cohort. Genet Test Mol Biomarkers 2018;22(6):374-83. PMID 29924655
17: Charrier EE, Montel L, Asnacios A, et al. The desmin network is a determinant of the cytoplasmic stiffness of myoblasts. Biol Cell 2018;110(4):77-90. PMID 29388701
18: Chen Z, Li R, Wang Y, et al. Features of myocardial injury detected by cardiac magnetic resonance in a patient with desmin-related restrictive cardiomyopathy. ESC Hear Fail 2021;8(6):5560-4. PMID 34612024
19: Clark JR, D'Agostino AN, Wilson J, Brooks RR, Cole GC. Autosomal dominant myofibrillar inclusion body myopathy: clinical, histologic, and ultrastructural characteristics. Neurology 1978:399.
20: Cortese A, Currò R, Ronco R, et al. Mutations in alpha-B-crystallin cause autosomal dominant axonal Charcot–Marie–Tooth disease with congenital cataracts. Eur J Neurol 2024;31(1):1-6. PMID 37772343
21: Dalakas MC, Park KY, Semino-Mora C, Lee S, Sivakumar K, Goldfarb LG. Desmin myopathy, a skeletal myopathy with cardiomyopathy caused by mutations in the desmin gene. New Eng J Med 2000;342:770-80. PMID 10717012
22: De Bleecker JL, Engel AG, Ertl BB. Myofibrillar myopathy with abnormal foci of desmin positivity. II. Immunocytochemical analysis reveals accumulation of multiple other proteins. J Neuropathol Exp Neurol 1996;55:563-77. PMID 8627347
23: de Fuenmayor-Fernández de la Hoz CP, Lupo V, Bermejo-Guerrero L, et al. Distal hereditary motor neuronopathy as a new phenotype associated with variants in BAG3. J Neurol 2024;271(2):986-94. PMID 37907725
24: Del Bigio MR, Chudley AE, Sarnat HB, et al. Infantile muscular dystrophy in Canadian aboriginals is an αB-crystallinopathy. Ann Neurol 2011;69(5):866-871. PMID 21337604
25: Delort F, Segard BD, Hakibilen C, et al. Alterations of redox dynamics and desmin post-translational modifications in skeletal muscle models of desminopathies. Exp Cell Res 2019;383(2):111539. PMID 31369751
26: Dhawan PS, Liewluck T, Knapik J, Milone M. Myofibrillar myopathy due to dominant LMNA mutations: a report of 2 cases. Muscle Nerve 2018;57(5):E124-6. PMID 29211919
27: Diermeier S, Iberl J, Vetter K, et al. Early signs of architectural and biomechanical failure in isolated myofibers and immortalized myoblasts from desmin-mutant knock-in mice. Sci Rep 2017;7(1):1391. PMID 28469177
28: Dimachkie MM, Barohn RJ. Distal myopathies. Neurol Clin 2014;32(3):817-42. PMID 25037092
29: Dimauro I, Antonioni A, Mercatelli N, Caporossi D. The role of αb-crystallin in skeletal and cardiac muscle tissues. Cell Stress Chaperones 2018;23(4):491-505. PMID 29190034
30: Donkervoort S, Kutzner CE, Hu Y, et al. Pathogenic variants in the myosin chaperone UNC-45B cause progressive myopathy with eccentric cores. Am J Hum Genet 2020;107(6):1078-95. PMID 33217308
31: Durmus H, Ayhan Ö, Çırak S, et al. Neuromuscular endplate pathology in recessive desminopathies: Lessons from man and mice. Neurology 2016;87(8):799-805. PMID 27440146
32: Edstrom L, Thornell LE, Albo J, Landin S, Samuelsson M. Myopathy with respiratory failure and typical myofibrillar lesions. J Neurol Sci 1990;96:211-28. PMID 2376753
33: Edstrom L, Thornell L, Eriksson A. A new type of hereditary distal myopathy with characteristic sarcoplasmic bodies and intermediate (skeletin) filaments. J Neurol Sci 1980;47:171-90. PMID 6251174
34: Even C, Abramovici G, Delort F, et al. Mutation in the core structure of desmin intermediate filaments affects myoblast elasticity. Biophys J 2017;113(3):627-36. PMID 28793217
35: Fardeau M, Godet-Guillian J, Tome FM, et al. A new familial muscular disorder demonstrated by the intra-sarcoplasmic accumulation of a granulo-filamentous material which is dense on electron microscopy. Rev Neurol 1978;134:411-25. PMID 570292
36: Fardeau M, Tome FM, Bakchine S, Rappaport L, Contard F, Chevallay M. Severe juvenile myopathy with ophthalmoplegia, intrasarcoplasmic inclusion bodies, and desmin accumulation. Neurology 1989;39(Suppl 1):337.
37: Feldkirchner S, Schessl J, Müller S, Schoser B, Hanisch FG. Patient-specific protein aggregates in myofibrillar myopathies: laser microdissection and differential proteomics for identification of plaque components. Proteomics 2012;12(23-24):3598-609. PMID 23044792
38: Feldkirchner S, Walter MC, Müller S, et al. Proteomic characterization of aggregate components in an intrafamilial variable FHL1-associated myopathy. Neuromuscul Disord 2013;23(5):418-26. PMID 23489660
39: Fichna JP, Maruszak A, Żekanowski C. Myofibrillar myopathy in the genomic context. J Appl Genet 2018;59(4):431-9. PMID 30203143
40: Fidzianska A, Goebel HH, Osborn M, Lenard G, Osse G, Langenbeck U. Mallory body-like inclusions in a hereditary congenital neuromuscular disease. Muscle Nerve 1983;6:195-200. PMID 6343859
41: Fidzianska A, Ryniewicz B, Barcikowska M, Goebel HH. A new familial congenital myopathy in children with desmin reacting dystrophin plaques. J Neurol Sci 1995;131:88-95. PMID 7561954
42: Garcia-Pelagio KP, Bloch RJ. Biomechanical properties of the sarcolemma and costameres of skeletal muscle lacking desmin. Front Physiol 2021;12:706806. PMID 34489727
43: Geisler N, Weber K. The amino acid sequence of chicken muscle desmin provides a common structural model for intermediate filament proteins. EMBO J 1982;1(12):1649-56. PMID 6202512
44: Goebel HH. Desmin-related neuromuscular disorders. Muscle Nerve 1995;18:1306-20. PMID 7565929
45: Goebel HH, Blaschek A. Protein aggregation in congenital myopathies. Semin Pediatr Neurol 2011;18(4):272-6. PMID 22172423
46: Goebel HH, Fardeau M. Desmin in myology. Neuromusc Disord 1995;5:161-6. PMID 7767096
47: Goebel HH, Muller J, Gillen HW, Merritt AD. Autosomal dominant "spheroid body myopathy." Muscle Nerve 1978;1:14-26. PMID 571956
48: Goebel HH, Schloon H, Lenard HG. Congenital myopathy with cytoplasmic bodies. Neuropediatrics 1981;12:166-80. PMID 6267501
49: Goebel HH, Voit T, Warlo I, Jacobs K, Johannsen U, Muller CR. Immunohistologic and electron microscopic abnormalities of desmin and dystrophin in familial cardiomyopathy and myopathy. Rev Neurol 1994;150:452-9. PMID 7747013
50: Goldfarb LG, Olive M, Vicart P, Goebel HH. Intermediate filament diseases: desminopathy. Adv Exp Med Biol 2008;642:131-64. PMID 19181099
51: Goldfarb LG, Park K, Cervenakova L, et al. Missense mutations in desmin associated with familial cardiac and skeletal myopathy. Nat Genet 1998;19(4):402-3. PMID 9697706
52: Guglielmi V, Marini M, Masson ÉF, et al. Abnormal expression of RNA polymerase II-associated proteins in muscle of patients with myofibrillar myopathies. Histopathology 2015;67(6):859-65. PMID 25891782
53: Hakibilen C, Delort F, Daher MT, et al. Desmin modulates muscle cell adhesion and migration. Front Cell Dev Biol 2022;10:783724. PMID 35350386
54: Hedberg C, Melberg A, Kuhl A, Jenne D, Oldfors A. Autosomal dominant myofibrillar myopathy with arrhythmogenic right ventricular cardiomyopathy 7 is caused by a DES mutation. Eur J Hum Genet 2012;20(9):984-5. PMID 22395865
55: Helliwell TR, Green AR, Green A, Edwards RH. Hereditary distal myopathy with granulo-filamentous cytoplasmic inclusions containing desmin, dystrophin and vimentin. J Neurol Sci 1994;124:174-87. PMID 7964869
56: Herrmann H, Aebi U. Intermediate filaments: molecular structure, assembly mechanism, and integration into functionally distinct intracellular Scaffolds. Annu Rev Biochem 2004;73:749-89. PMID 15189158
57: Horowitz SH, Schmalbruch H. Autosomal dominant distal myopathy with desmin storage: a clinicopathologic and electrophysiologic study of a large kinship. Muscle Nerve 1994;17:151-60. PMID 8114783
58: Hovhannisyan Y, Li Z, Callon D, et al. Critical contribution of mitochondria in the development of cardiomyopathy linked to desmin mutation. Stem Cell Res Ther 2024;15(1):1-23. PMID 38167524
59: Jaffer F, Murphy SM, Scoto M, et al. BAG3 mutations: another cause of giant axonal neuropathy. J Peripher Nerv Syst 2012;17(2):210-16. PMID 22734908
60: Janzer RC, Lobrinus JA, Genton CY, Kuntzer T. Familial distal myopathy and cardiomyopathy with accumulation of subsarcolemmal desmin-containing inclusions in skeletal and heart muscle. Clin Neuropathol 1996;15:276.
61: Jerusalem F, Ludin H, Bischoff A, Hartmann G. Cytoplasmic body neuromyopathy presenting as respiratory failure and weight loss. J Neurol Sci 1979;41:1-9. PMID 220387
62: Joanne P, Hovhannisyan Y, Bencze M, et al. Absence of desmin results in impaired adaptive response to mechanical overloading of skeletal muscle. Front Cell Dev Biol 2021;9:662133. PMID 34336827
63: Jungbluth H. Myopathology in times of modern imaging. Neuropathol Appl Neurobiol 2017;43(1):24-43. PMID 28111795
64: Kedia N, Arhzaouy K, Pittman SK, et al. Desmin forms toxic, seeding-competent amyloid aggregates that persist in muscle fibers. Proc Natl Acad Sci U S A 2019;116(34):16835-40. PMID 31371504
65: Kinoshita M, Satoyoshi E, Suzuki Y. Atypical myopathy with myofibrillar aggregates. Arch Neurol 1975;32:417-20. PMID 165803
66: Kley RA, Olivé M, Schröder R. New aspects of myofibrillar myopathies. Curr Opin Neurol 2016;29(5):628-34. PMID 27389816
67: Kley RA, Serdaroglu-Oflazer P, Leber Y, et al. Pathophysiology of protein aggregation and extended phenotyping in filaminopathy. Brain 2012;135(Pt 9):2642-60. PMID 22961544
68: Kölbel H, Roos A, van der Ven PFM, et al. First clinical and myopathological description of a myofibrillar myopathy with congenital onset and homozygous mutation in FLNC. Hum Mutat 2020;41(9):1600-14. PMID 32516863
69: Koopmann TT, Jamshidi Y, Naghibi-Sistani M, et al. Biallelic loss of LDB3 leads to a lethal pediatric dilated cardiomyopathy. Eur J Hum Genet 2023;31(1):97-104. PMID 36253531
70: Lacson AG, Seshia SS, Sarnat HB, et al. Autosomal recessive, fatal infantile hypertonic muscular dystrophy among Canadian natives. Can J Neurol Sci 1994;21(3):203-12. PMID 8000975
71: Latham GJ, Lopez G. Anesthetic considerations in myofibrillar myopathy. Paediatr Anaesth 2015;25(3):231-8. PMID 25216331
72: Lee HH, Wong S, Sheng B, et al. Clinical and pathological characterization of FLNC‐related myofibrillar myopathy caused by founder variant c.8129G > A in Hong Kong Chinese. Clin Genet 2020;97(5):747-57. PMID 32022900
73: Levin J, Bulst S, Thirion C, et al. Divergent molecular effects of desmin mutations on protein assembly in myofibrillar myopathy. J Neuropathol Exp Neurol 2010;69:415-24. PMID 20448486
74: Li M, Andersson-Lendahl M, Sejersen T, Arner A. Knockdown of desmin in zebrafish larvae affects interfilament spacing and mechanical properties of skeletal muscle. J Gen Physiol 2013;141(3):335-45. PMID 23440276
75: Liewluck T, Milone M. Untangling the complexity of limb-girdle muscular dystrophies. Muscle Nerve 2018;58(2):167-7. PMID 29350766
76: Lu XG, Yu U, Han CX, Mai JH, Liao JX, Hou YQ. c.3G>A mutation in the CRYAB gene that causes fatal infantile hypertonic myofibrillar myopathy in the Chinese population. J Integr Neurosci 2021;20(1):143. PMID 33834702
77: Ma K, Luo D, Tian T, et al. A novel homozygous initiation codon variant associated with infantile alpha-Bcrystallinopathy in a Chinese family. Mol Genet Genomic Med 2019;7(8):e825. PMID 31215171
78: MacDonald RD, Engel AG. The cytoplasmic body: another structural anomaly of the z disk. Acta Neuropathol (Berl) 1969;14:99-107. PMID 4242247
79: Maerkens A, Olivé M, Schreiner A, et al. New insights into the protein aggregation pathology in myotilinopathy by combined proteomic and immunolocalization analyses. Acta Neuropathol Commun 2016;4:8. PMID 26842778
80: Mair D, Biskup S, Kress W, et al. Differential diagnosis of vacuolar myopathies in the NGS era. Brain Pathol 2020;30(5):877-96. PMID 32419263
81: Mitzelfelt KA, Limphong P, Choi MJ, et al. Human 343delt HSPB5 chaperone associated with early-onset skeletal myopathy causes defects in protein solubility. J Biol Chem 2016;291(29):1439-53. PMID 27226619
82: Munoz-Marmol AM, Strasser G, Isamat M, et al. A dysfunctional desmin mutation in a patient with severe generalized myopathy. Proc Natl Acad Sci U S A 1998;95:11312–7. PMID 9736733
83: Muntoni F, Catani G, Mateddu A, et al. Familial cardiomyopathy, mental retardation and myopathy associated with desmin-type intermediate filaments. Neuromusc Disord 1994;4(3):233-41. PMID 7919971
84: Nakano S, Engel A, Waclawik AJ, Emslie-Smith AM, Busis NA. Myofibrillar myopathy with abnormal foci of desmin positivity. I. Light and electron microscopy analysis of 10 cases. J Neuropathol Exp Neurol 1996;55:549-62. PMID 8627346
85: Nakashima N, Tamura Z, Okamoto S, Goto H. Inclusion bodies in human neuromuscular disorder. Arch Neurol 1970;22:270-8. PMID 5411681
86: Nicolau S, Howe BM, Naddaf E. Novel desmin mutation causing myofibrillar myopathy in a Hmong family. Front Neurol 2020a;10:1375. PMID 31998224
87: Nicolau S, Liewluck T, Elliott JL, Engel AG, Milone M. A novel heterozygous mutation in the C-terminal region of HSPB8 leads to limb-girdle rimmed vacuolar myopathy. Neuromuscul Disord 2020b;30(3):236-40. PMID 32165108
88: Niu Z, Pontifex CS, Berini S, et al. Myopathy with SQSTM1 and TIA1 variants: Clinical and pathological features. Front Neurol 2018;9:147. PMID 29599744
89: O’Grady GL, Best HA, Sztal TE, et al. Variants in the oxidoreductase PYROXD1 cause early-onset myopathy with internalized nuclei and myofibrillar disorganization. Am J Hum Genet 2016;99(5):1086-105. PMID 27745833
90: Ohlsson M, Hedberg C, Bradvik B, et al. Hereditary myopathy with early respiratory failure associated with a mutation in A-band titin. Brain 2012;135(Pt 6):1682-94. PMID 22577218
91: Onore ME, Savarese M, Picillo E, Passamano L, Nigro V, Politano L. Bi-allelic DES gene variants causing autosomal recessive myofibrillar myopathies affecting both skeletal muscles and cardiac function. Int J Mol Sci 2022;23(24):15906. PMID 36555543
92: Osborn M, Goebel HH. The cytoplasmic bodies in a congenital myopathy can be stained with antibodies to desmin, the muscle-specific intermediate filament protein. Acta Neuropathol (Berl) 1983;62:149-52. PMID 6318501
93: Panicucci C, Traverso M, Baratto S, et al. Novel TRIM32 mutation in sarcotubular myopathy. Acta Myol 2019;38(1):8-12. PMID 31309175
94: Paulin D, Hovhannisyan Y, Kasakyan S, Agbulut O, Li Z, Xue Z. Synemin-related skeletal and cardiac myopathies: an overview of pathogenic variants. Am J Physiol Cell Physiol 2020;318(4):C709-18. PMID 32023076
95: Paulin D, Huet A, Khanamyrian L, Xue Z. Desminopathies in muscle disease. J Pathol 2004;204(4):418-27. PMID 15495235
96: Pellissier JF, Pouget J, Charpin C, Figarella D. Myopathy associated with desmin type intermediate filaments. An immunoelectron microscopic study. J Neurol Sci 1989;89:49-61. PMID 2926442
97: Pfeffer G, Povitz M, Gibson GJ, Chinnery PF. Diagnosis of muscle diseases presenting with early respiratory failure. J Neurol 2015;262(5):1101-14. PMID 25377282
98: Pfeffer G, Sambuughin N, Olivé M, et al. A new disease allele for the p.C30071R mutation in titin causing hereditary myopathy with early respiratory failure. Neuromuscul Disord 2014;24(3):241-4. PMID 24444549
99: Polavarapu K, O’Neil D, Thompson R, et al. Partial loss of desmin expression due to a leaky splice site variant in the human DES gene is associated with neuromuscular transmission defects. Neuromuscul Disord 2024;39:10-8. PMID 3869730
100: Porte A, Stoeckel M, Sacrez A, Batzenschlager A. Unusual familial cardiomyopathy with storage of intermediate filaments in the cardiac muscular cells. Virchows Arch A Pathol Anat Histol 1980;386:43-58. PMID 7405006
101: Potulska-Chromik A, Jędrzejowska M, Gos M, et al. Pathogenic mutations and putative phenotype-affecting variants in polish myofibrillar myopathy patients. J Clin Med 2021;10(5):914. PMID 33652732
102: Previtali SC, Scarlato M, Vezzulli P, et al. Expanding the central nervous system disease spectrum associated with FLNC mutation. Muscle Nerve 2019;5:33-7. PMID 30734317
103: Price MG. Molecular analysis of intermediate filament cytoskeleton-putative load-bearing structure. Am J Physiol 1984;246:H566-72. PMID 6539082
104: Quax W, Meera Khan P, Quax-Jeuken Y, Bloemendal H. The human desmin and vimentin genes are located on different chromosomes. Gene 1985;38:189-96. PMID 4065572
105: Renard D, Castelnovo G, Fernandez C, et al. Camptocormia as presenting sign in myofibrillar myopathy. Neuromuscul Disord 2012;22(11):987-9. PMID 22749474
106: Ruparelia AA, McKaige EA, Williams C, et al. Metformin rescues muscle function in BAG3 myofibrillar myopathy models. Autophagy 2020;00(00):1-17. PMID 33030392
107: Ruparelia AA, Oorschot V, Vaz R, Ramm G, Bryson-Richardson RJ. Zebrafish models of BAG3 myofibrillar myopathy suggest a toxic gain of function leading to BAG3 insufficiency. Acta Neuropathol 2014;128(6):821-33. PMID 25273835
108: Ruparelia AA, Zhao M, Currie PD, Bryson-Richardson RJ. Characterization and investigation of zebrafish models of filamin-related myofibrillar myopathy. Hum Mol Genet 2012;21(18):4073-83. PMID 22706277
109: Sabatelli M, Bertini E, Ricci E, et al. Peripheral neuropathology with giant axons and cardiomyopathy associated with desmin type intermediate filaments in skeletal muscle. J Neurol Sci 1992;109(1):1-10. PMID 1517757
110: Sanbe A, Osinska H, Saffitz JE, et al. Desmin-related cardiomyopathy in transgenic mice: a cardiac amyloidosis. Proc Natl Acad Sci U S A 2004;101(27):10132-6. PMID 15220483
111: Sandell S, Huovinen S, Palmio J, et al. Diagnostically important muscle pathology in DNAJB6 mutated LGMD1D. Acta Neuropathol Commun 2016;4:9. PMID 26847086
112: Sarnat HB. Vimentin and desmin in maturing skeletal muscle and developmental myopathies. Neurology 1992;42:1616-24. PMID 1641160
113: Sarnat HB. Does increased desmin in myofibres constitute a storage disease. Neuromuscul Disord 1993;3:3-4. PMID 8329887
114: Schessl J, Bach E, Rost S, et al. Novel recessive myotilin mutation causes severe myofibrillar myopathy. Neurogenetics 2014;15(3):151-6. PMID 24928145
115: Schessl J, Zou Y, McGrath MJ, et al. Proteomic identification of FHL1 as the protein mutated in human reducing body myopathy. J Clin Invest 2008;118(3):904-12. PMID 18274675
116: Schroder JM, Sommer C, Schmidt B. Desmin and actin associated with cytoplasmic bodies in skeletal muscle fibers: immunocytochemical and fine structural studies, with a note on unusual 18-20-nm filaments. Acta Neuropathol 1990;80:406-14. PMID 2173329
117: Selcen D. Myofibrillar myopathies. Curr Opin Neurol 2008;21(5):585-9. PMID 18769253
118: Selcen D. Myofibrillar myopathies. Neuromuscul Disord 2011;21(3):161-71. PMID 21256014
119: Selcen D. Severe congenital actin related myopathy with myofibrillar myopathy features. Neuromuscul Disord 2015;25(6):488-92. PMID 25913210
120: Selcen D, Engel AG. Myofibrillar myopathy caused by novel dominant negative alpha B-crystallin mutations. Ann Neurol 2003;54:804-10. PMID 14681890
121: Selcen D, Engel AG. Mutations in myotilin cause myofibrillar myopathy. Neurology 2004;62:1363-71. PMID 15111675
122: Selcen D, Engel AG. Mutations in ZASP define a novel form of muscular dystrophy in humans. Ann Neurol 2005;57:269-76. PMID 15668942
123: Selcen D, Engel AG. Myofibrillar myopathy. GeneReviews 2006.
124: Selcen D, Engel AG. Myofibrillar myopathies. Handb Clin Neurol 2011;101:143-54. PMID 21496631
125: Selcen D, Muntoni F, Burton BK, et al. Mutation in BAG3 causes severe dominant childhood muscular dystrophy. Ann Neurol 2009;65:83-9. PMID 19085932
126: Sharma S, Conover GM, Elliott JL, Der Perng M, Herrmann H, Quinlan RA. ΑB-crystallin is a sensor for assembly intermediates and for the subunit topology of desmin intermediate filaments. Cell Stress Chaperones 2017;22(4):613-26. PMID 28470624
127: Shelly S, Talha N, Pereira NL, Engel AG, Johnson JN, Selcen D. Expanding spectrum of desmin-related myopathy, long-term follow-up, and cardiac transplantation. Neurology 2021;97(11):e1150-8. PMID 34315782
128: Shin JW, Kim KH, Lee Y, Choi DE LJ. Personalized allele-specific CRISPR-Cas9 strategies for myofibrillar myopathy 6. medRxiv 2024;2024. PMID 38352343
129: Silva AMS, Rodrigo P, Moreno CAM, et al. The location of disease-causing DES variants determines the severity of phenotype and the morphology of sarcoplasmic aggregates. J Neuropathol Exp Neurol 2022;81(9):746-57. PMID 35898174
130: Stoeckel ME, Osborn M, Porte A, Sacrez A, Batzenschlager A, Weber K. An unusual familial cardiomyopathy characterized by aberrant accumulations of desmin-type intermediate filaments. Virchows Arch A 1981:393:53-60. PMID 6889780
131: Strach K, Sommer T, Grohe C, et al. Clinical, genetic, and cardiac magnetic resonance imaging findings in primary desminopathies. Neuromuscul Disord 2008;18(6):475-82. PMID 18504128
132: Tajsharghi H, Darin N, Tulinius M, Oldfors A. Early onset myopathy with a novel mutation in the Selenoprotein N gene (SEPN1). Neuromuscul Disord 2005;15(4):299-302. PMID 15792869
133: Tasca G, Odgerel Z, Monforte M, et al. Novel FLNC mutation in a patient with myofibrillar myopathy in combination with late-onset cerebellar ataxia. Muscle Nerve 2012;46(2):275-82. PMID 22806379
134: Vajsar J, Becker LE, Freedom RM, Murphy EG. Familial desminopathy: myopathy with accumulation of desmin-type intermediate filaments. J Neurol Neurosurg Psychiatry 1993;56:644-8. PMID 8509778
135: van Spaendonck-Zwarts K, van Hessem L, Jongbloed JD, et al. Desmin-related myopathy. Clin Genet 2011;80(4):354-66. PMID 20718792
136: Vicart P, Caron A, Guicheney P, et al. A missense mutation in the alpha B-crystallin chaperone gene causes a desmin-related myopathy. Nat Genet 1998;20(1):92-5. PMID 9731540
137: Vicart P, Dupret JM, Hazan J, et al. Human desmin gene: cDNA sequence, regional localization and exclusion of the locus in a familial desmin-related myopathy. Hum Genet 1996;98(4):422-9. PMID 8792816
138: Viegas-Pequignot E, Li LZ, Dutrillaux B, Apiou F, Paulin D. Assignment of human desmin gene to band 2q35 by nonradioactive in situ hybridization. Hum Genet 1989;83(1):33-6. PMID 2670738
139: Vorgerd M, van der Ven PF, Bruchertseifer V, et al. A mutation in the dimerization domain of filamin c causes a novel type of autosomal dominant myofibrillar myopathy. Am J Hum Genet 2005;77:297-304. PMID 15929027
140: Wahbi K, Béhin A, Charron P, et al. High cardiovascular morbidity and mortality in myofibrillar myopathies due to DES gene mutations: a 10-year longitudinal study. Neuromuscul Disord 2012;22(3):211-8. PMID 22153487
141: Weihl CC, Iyadurai S, Baloh RH, et al. Autophagic vacuolar pathology in desminopathies. Neuromuscul Disord 2015;25(3):199-206. PMID 25557463
142: Weihl CC, Töpf A, Bengoechea R, et al. Loss of function variants in DNAJB4 cause a myopathy with early respiratory failure. Acta Neuropathol 2023;145(1):127-43. PMID 36264506
143: Winter L, Goldmann WH. Biomechanical characterization of myofibrillar myopathies. Cell Biol Int 2015;39(4):361-3. PMID 25264173
144: Winter L, Wittig I, Peeva V, et al. Mutant desmin substantially perturbs mitochondrial morphology, function and maintenance in skeletal muscle tissue. Acta Neuropathol 2016;132(3):453-73. PMID 27393313
145: Wolburg H, Schlote W, Langohr HD, Peiffer J, Reiher KH, Heckl RW. Slowly progressive congenital myopathy with cytoplasmic bodies: report of two cases and a review of the literature. Clin Neuropathol 1982;1:55-66. PMID 6301720
146: Zheng Q, Su H, Ranek MJ, Wang X. Autophagy and p62 in cardiac proteinopathy. Circ Res 2011;109(3):296-308. PMID 21659648

Contributors

All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.

Author

Jean K Mah MD

Dr. Mah of the University of Calgary has no relevant financial relationships to disclose.
See Profile

Editor

Harvey B Sarnat MD FRCPC MS

Dr. Sarnat of the University of Calgary has no relevant financial relationships to disclose.
See Profile

Former Authors

Victoria Anne Fabian MD
Goknur Haliloglu MD
Haluk Topaloglu MD

Patient Profile

Age range of presentation: 0 month to 64 years
Sex preponderance: male=female
Heredity: heredity may be a factor
Population groups selectively affected: none selectively affected
Occupation groups selectively affected: none selectively affected

ICD & OMIM codes

ICD-10: Other myopathies: G72.8
ICD-11: Other specified congenital myopathy with structural abnormalities: 8C72.0Y
OMIM: Desmin body myofibrillar myopathy: #601419

This is an article preview.
Start a Free Account
to access the full version.

Nearly 3,000 illustrations, including video clips of neurologic disorders.
Every article is reviewed by our esteemed Editorial Board for accuracy and currency.
Full spectrum of neurology in 1,200 comprehensive articles.
Listen to MedLink on the go with Audio versions of each article.

Questions or Comment?

MedLink®, LLC

3525 Del Mar Heights Rd, Ste 304
San Diego, CA 92130-2122

Toll Free (U.S. + Canada): 800-452-2400

US Number: +1-619-640-4660

Support: service@medlink.com

Editor: editor@medlink.com

ISSN: 2831-9125

Desmin body myofibrillar myopathy

Associated Disorders

Desmin storage myopathy
Desminopathy
Intermediate filament myopathy
Mallory body myopathy
Myopathy with granulofilamentous inclusions
- Spheroid body myopathy

Differential Diagnosis

distal myopathies
myotonic dystrophy
distal muscular dystrophy
scapuloperoneal syndrome
Welander disease
- myotonic dystrophy
- facioscapulohumeral dystrophy
- inclusion-body myositis
- congenital myopathy
- scapuloperoneal syndrome
- peripheral neuropathy

Also Relevant

Distal myopathies
Facioscapulohumeral muscular dystrophy
Reducing body myopathy

Clinical Categories

Web References

Guidelines

AAN: Neuromuscular guidelines

Desmin body myofibrillar myopathy …

Desmin body myofibrillar myopathy

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Diagnostic workup

Management

Special considerations

Anesthesia

Media

References

Contributors

Author

Editor

Former Authors

Patient Profile

ICD & OMIM codes

This is an article preview.
Start a Free Account
to access the full version.

Questions or Comment?

Also in This Category

Vein of Galen malformations

Distal myopathies

Epileptic lesions due to malformation of cortical development

Amyotrophic lateral sclerosis

Agenesis of the corpus callosum

Epidermal nevus syndromes: neurologic phenotypes

ALS-like disorders of the Western Pacific

Norrie disease

Desmin body myofibrillar myopathy

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Diagnostic workup

Management

Special considerations

Anesthesia

Media

References

Contributors

Author

Editor

Former Authors

Patient Profile

ICD & OMIM codes

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

Vein of Galen malformations

Distal myopathies

Epileptic lesions due to malformation of cortical development

Amyotrophic lateral sclerosis

Agenesis of the corpus callosum

Epidermal nevus syndromes: neurologic phenotypes

ALS-like disorders of the Western Pacific

Norrie disease

This is an article preview.
Start a Free Account
to access the full version.