Hyaline Body Myopathy: Adulthood Manifestations

ABSTRACT:Background:Hyaline body myopathy (HBM) is a rare chronic nonprogressive congenital myopathy, with variable patterns of inheritance.Methods:We describe a patient with congenital HBM with progression of weakness and increasing muscle pain in adulthood. Three muscle biopsies, done at various times in her life, are reported.Results:Symptoms started during childhood; however, as an adult, following a period of stability with no progression of the disease, the patient became symptomatic with worsening proximal limb weakness, severe aching pain and hypertrophy of calves. Moderate elevations of serum creatine kinase and myopathic features were noted on electrophysiologic testing. Muscle pathology showed significant fatty infiltration of skeletal muscle and increased number of fibers with internal nuclei. Histology demonstrated the presence of subsarcolemmal, well-delineated hyaline areas, which on histochemical studies was shown to be limited to type1 fibers. The hyaline bodies were dark with pH 4.2 ATPase and with immunohistochemical studies reacted only with myosin heavy chain slow. Electron microscopy showed the hyaline bodies to be composed of nonmembrane bound, fairly even sized granular material, which merged with the adjacent myofibrils. Earlier muscle biopsies, done during childhood, also revealed presence of similar subsarcolemmal hyaline deposits.Conclusion:There appears to be a pattern of presentation with adulthood progression in HBM, which has not been described before. Further case studies are required to understand the clinical progression in HBM.

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Clinical, genetic, and pathologic characterization of FKRP Mexican founder mutation c.1387A>G

Neurology Genetics ◽

10.1212/nxg.0000000000000315 ◽

2019 ◽

Vol 5 (2) ◽

pp. e315 ◽

Cited By ~ 4

Author(s):

Angela J. Lee ◽

Karra A. Jones ◽

Russell J. Butterfield ◽

Mary O. Cox ◽

Chamindra G. Konersman ◽

...

Keyword(s):

Muscular Dystrophy ◽

Founder Mutation ◽

Congenital Muscular Dystrophy ◽

Clinical Severity ◽

Muscle Pathology ◽

Clinical Genetic ◽

End Stage ◽

Muscle Biopsies ◽

Normal Cognition

ObjectiveTo characterize the clinical phenotype, genetic origin, and muscle pathology of patients with the FKRP c.1387A>G mutation.MethodsStandardized clinical data were collected for all patients known to the authors with c.1387A>G mutations in FKRP. Muscle biopsies were reviewed and used for histopathology, immunostaining, Western blotting, and DNA extraction. Genetic analysis was performed on extracted DNA.ResultsWe report the clinical phenotypes of 6 patients homozygous for the c.1387A>G mutation in FKRP. Onset of symptoms was <2 years, and 5 of the 6 patients never learned to walk. Brain MRIs were normal. Cognition was normal to mildly impaired. Microarray analysis of 5 homozygous FKRP c.1387A>G patients revealed a 500-kb region of shared homozygosity at 19q13.32, including FKRP. All 4 muscle biopsies available for review showed end-stage dystrophic pathology, near absence of glycosylated α-dystroglycan (α-DG) by immunofluorescence, and reduced molecular weight of α-DG compared with controls and patients with homozygous FKRP c.826C>A limb-girdle muscular dystrophy.ConclusionsThe clinical features and muscle pathology in these newly reported patients homozygous for FKRP c.1387A>G confirm that this mutation causes congenital muscular dystrophy. The clinical severity might be explained by the greater reduction in α-DG glycosylation compared with that seen with the c.826C>A mutation. The shared region of homozygosity at 19q13.32 indicates that FKRP c.1387A>G is a founder mutation with an estimated age of 60 generations (∼1,200–1,500 years).

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Duchenne and Becker muscular dystrophy: a molecular and immunohistochemical approach

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x2007000100016 ◽

2007 ◽

Vol 65 (1) ◽

pp. 73-76 ◽

Cited By ~ 13

Author(s):

Aline Andrade Freund ◽

Rosana Herminia Scola ◽

Raquel Cristina Arndt ◽

Paulo José Lorenzoni ◽

Claudia Kamoy Kay ◽

...

Keyword(s):

Muscular Dystrophy ◽

Muscular Atrophy ◽

Hot Spot ◽

Dystrophin Gene ◽

Becker Muscular Dystrophy ◽

Congenital Myopathy ◽

Specific Method ◽

Dystrophin Deficiency ◽

Muscle Biopsies ◽

Female Carriers

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are caused by mutations in the dystrophin gene. We studied 106 patients with a diagnosis of probable DMD/BMD by analyzing 20 exons of the dystrophin gene in their blood and, in some of the cases, by immunohistochemical assays for dystrophin in muscle biopsies. In 71.7% of the patients, deletions were found in at least one of the exons; 68% of these deletions were in the hot-spot 3' region. Deletions were found in 81.5% of the DMD cases and in all the BMD cases. The cases without deletions, which included the only woman in the study with DMD, had dystrophin deficiency. The symptomatic female carriers had no deletions but had abnormal dystrophin distribution in the sarcolemma (discontinuous immunostains). The following diagnoses were made for the remaining cases without deletions with the aid of a muscle biopsy: spinal muscular atrophy, congenital myopathy; sarcoglycan deficiency and unclassified limb-girdle muscular dystrophy. Dystrophin analysis by immunohistochemistry continues to be the most specific method for diagnosis of DMD/BMD and should be used when no exon deletions are found in the dystrophin gene in the blood.

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CGG expansion in NOTCH2NLC is associated with oculopharyngodistal myopathy with neurological manifestations

10.1101/2020.10.16.20213785 ◽

2020 ◽

Author(s):

Masashi Ogasawara ◽

Aritoshi Iida ◽

Theerawat Kumutpongpanich ◽

Ayami Ozaki ◽

Yasushi Oya ◽

...

Keyword(s):

Electron Microscopy ◽

Muscle Weakness ◽

Clinical Information ◽

Muscle Disease ◽

Muscle Pathology ◽

Limb Weakness ◽

Cgg Repeat ◽

Rimmed Vacuoles ◽

Ubiquitinated Proteins ◽

Repeat Expansions

ABSTRACTBackgroundOculopharyngodistal myopathy (OPDM) is a rare hereditary muscle disease characterized by progressive distal limb weakness, ptosis, ophthalmoplegia, bulbar muscle weakness and rimmed vacuoles on muscle biopsy. Recently, CGG repeat expansions in the noncoding regions of two genes, LRP12 and GIPC1, have been reported to be causative for OPDM. Furthermore, neuronal intranuclear inclusion disease (NIID) has been recently reported to be caused by CGG repeat expansions in NOTCH2NLC.ObjectivesTo identify and to clinicopathologically characterize OPDM patients who have CGG repeat expansions in NOTCH2NLC (OPDM_NOTCH2NLC).MethodsTwo hundred eleven patients from 201 families, who were clinically or clinicopathologically diagnosed with OPDM or oculopharyngeal muscular dystrophy, were screened for CGG expansions in NOTCH2NLC by repeat primed-PCR. Clinical information and muscle pathology slides of the identified OPDM_NOTCH2NLC patients were re-reviewed. Intra-myonuclear inclusions were further evaluated by immunohistochemistry and electron microscopy.ResultsSeven Japanese OPDM patients had CGG repeat expansions in NOTCH2NLC. All seven patients clinically had ptosis, ophthalmoplegia, dysarthria, and muscle weakness, and myopathologically had intra-myonuclear inclusions stained with anti-poly-ubiquitinated proteins, anti-SUMO1 and anti-p62 antibodies, which are diagnostic of NIID typically on skin biopsy, in addition to rimmed vacuoles. Sample for electron microscopy was available only from one patient, which showed intranuclear inclusions of 12.6 ± 1.6 nm in diameter.ConclusionsWe identified seven OPDM_NOTCH2NLC patients. Our patients had various additional central and/or peripheral nervous system involvement, albeit all being clinicopathologically compatible; thus, diagnosed as having OPDM, expanding a phenotype of the neuromyodegenerative disease caused by CGG repeat expansions in NOTCH2NLC.

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Adding quantitative muscle MRI to the FSHD clinical trial toolbox

Neurology ◽

10.1212/wnl.0000000000004647 ◽

2017 ◽

Vol 89 (20) ◽

pp. 2057-2065 ◽

Cited By ~ 30

Author(s):

Karlien Mul ◽

Sanne C.C. Vincenten ◽

Nicol C. Voermans ◽

Richard J.L.F. Lemmers ◽

Patrick J. van der Vliet ◽

...

Keyword(s):

Clinical Trial ◽

Clinical Outcome ◽

Outcome Measures ◽

Fatty Infiltration ◽

Correlation Coefficients ◽

Muscle Pathology ◽

Muscle Mri ◽

Leg Muscles ◽

Fat Fraction ◽

Leg Muscle

Objective:To add quantitative muscle MRI to the clinical trial toolbox for facioscapulohumeral muscular dystrophy (FSHD) by correlating it to clinical outcome measures in a large cohort of genetically and clinically well-characterized patients with FSHD comprising the entire clinical spectrum.Methods:Quantitative MRI scans of leg muscles of 140 patients with FSHD1 and FSHD2 were assessed for fatty infiltration and TIRM hyperintensities and were correlated to multiple clinical outcome measures.Results:The mean fat fraction of the total leg musculature correlated highly with the motor function measure, FSHD clinical score, Ricci score, and 6-minute walking test (correlation coefficients −0.845, 0.835, 0.791, −0.701, respectively). Fat fraction per muscle group correlated well with corresponding muscle strength (correlation coefficients up to −0.82). The hamstring muscles, adductor muscles, rectus femoris, and gastrocnemius medialis were affected most frequently, also in early stage disease and in patients without leg muscle weakness. Muscle involvement was asymmetric in 20% of all muscle pairs and fatty infiltration within muscles showed a decrease from distal to proximal of 3.9%. TIRM hyperintense areas, suggesting inflammation, were found in 3.5% of all muscles, with and without fatty infiltration.Conclusions:We show a strong correlation between quantitative muscle MRI and clinical outcome measures. Muscle MRI is able to detect muscle pathology before clinical involvement of the leg muscles. This indicates that quantitative leg muscle MRI is a promising biomarker that captures disease severity and motor functioning and can thus be included in the FSHD trial toolbox.

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Chronic Benign Congenital Myopathy: Fingerprint Body Type

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s031716710001965x ◽

1974 ◽

Vol 1 (2) ◽

pp. 106-113 ◽

Cited By ~ 8

Author(s):

A.S. Gordon ◽

N.B. Rewcastle ◽

J.G. Humphrey ◽

B.M. Stewart

Keyword(s):

Fatty Infiltration ◽

Congenital Myopathy ◽

Normal Serum ◽

Type I ◽

Body Type ◽

Electron Microscopic ◽

Muscle Enzyme ◽

Muscle Disorders ◽

Good Differentiation ◽

Fingerprint Bodies

SUMMARYThe term “benign congenital myopathy” describes a group of muscle disorders characterized by proximal or diffuse muscle weakness, a relatively non-progressive course, normal serum muscle enzyme assays and the presence of a distinctive morphological feature. We report here a 55 year old woman, with fingerprint body myopathy who exhibits all of the above features. She has been affected from birth, able to walk since the age of 12, and has not deteriorated in the past thirty years. Muscle biopsy reveals fatty infiltration, numerous small fibers undergoing structural change, good differentiation into type I and II fibers, and excessive intracellular lipid and lipochrome. Only on electron microscopic study is the distinctive feature of numerous subsarcolemmal round to ovoid fingerprint bodies observed. Many fibers also contain large collections of tubular aggregates, filamentous bodies, and autophagic vacuoles.The fingerprint bodies are similar to the ones described by A. Engel in a 5 year old girl. Thus, a rare opportunity is provided to study an individual who has had this disease for over fifty years.

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Neutral lipid storage disease with myopathy in China: a large multicentric cohort study

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-019-1209-z ◽

2019 ◽

Vol 14 (1) ◽

Cited By ~ 2

Author(s):

Wei Zhang ◽

Bing Wen ◽

Jun Lu ◽

Yawen Zhao ◽

Daojun Hong ◽

...

Keyword(s):

Neutral Lipid ◽

Storage Disease ◽

Fatty Infiltration ◽

Disease Onset ◽

Lipid Storage ◽

Muscle Pathology ◽

Lipid Storage Disease ◽

Rimmed Vacuoles ◽

Skeletal Myopathy ◽

Neutral Lipid Storage Disease

Abstract Background Neutral lipid storage disease with myopathy (NLSDM) is a rare clinical heterogeneous disorder caused by mutations in the patatin-like phospholipase domain-containing 2 (PNPLA2) gene. NLSDM usually presents skeletal myopathy, cardiomyopathy and the multiple organs dysfunction. Around 50 cases of NLSDM have been described worldwide, whereas the comprehensive understanding of this disease are still limited. We therefore recruit NLSDM patients from 10 centers across China, summarize the clinical, muscle imaging, pathological and genetic features, and analyze the genotype-phenotype relationship. Results A total of 45 NLSDM patients (18 men and 27 women) were recruited from 40 unrelated families. Thirteen patients were born from consanguineous parents. The phenotypes were classified as asymptomatic hyperCKemia (2/45), pure skeletal myopathy (18/45), pure cardiomyopathy (4/45), and the combination of skeletal myopathy and cardiomyopathy (21/45). Right upper limb weakness was the early and prominent feature in 61.5% of patients. On muscle MRI, the long head of the biceps femoris, semimembranosus and adductor magnus on thighs, the soleus and medial head of the gastrocnemius on lower legs showed the most severe fatty infiltration. Thirty-three families were carrying homozygous mutations, while seven families were carrying compound heterozygous mutations. A total of 23 mutations were identified including 11 (47.8%) point mutations, eight (34.8%) deletions and four (17.4%) insertions. c.757 + 1G > T, c.245G > A and c.187 + 1G > A were the three most frequent mutations. Among four groups of phenotypes, significant differences were shown in disease onset (< 20 years versus ≥20 years old, p = 0.003) and muscle pathology (with rimmed vacuoles versus without rimmed vacuoles, p = 0.001). PNPLA2 mutational type or functional defects did not show great impact on phenotypes. Conclusion We outline the clinical and genetic spectrum in a large cohort of NLSDM patients. Selective muscle fatty infiltration on posterior compartment of legs are characteristic of NLSDM. Chinese patients present with distinctive and relative hotspot PNPLA2 mutations. The disease onset age and pathological appearance of rimmed vacuoles are proved to be related with the clinical manifestations. The phenotypes are not strongly influenced by genetic defects, suggesting the multiple environmental risk factors in the development of NLSDM.

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Muscle pathology in juvenile dermatomyositis

Sao Paulo Medical Journal ◽

10.1590/s1516-31801997000500009 ◽

1997 ◽

Vol 115 (5) ◽

pp. 1555-1559 ◽

Cited By ~ 9

Author(s):

Edenilson Eduardo Calore ◽

Maria José Cavaliere ◽

Nilda Maria Perez

Keyword(s):

Muscle Biopsy ◽

Public Health Service ◽

Vastus Lateralis ◽

Inflammatory Myopathy ◽

Muscle Pathology ◽

Clinical Activity ◽

Variable Intensity ◽

Muscle Necrosis ◽

One Year ◽

Muscle Biopsies

OBJECTIVE: To study muscle biopsies, using histochemistry, on ten children with infantile dermatomyositis. DESIGN: Series of ten patients (of whom eight patients had received treatment and two had not) were submitted to muscle biopsy in order to diagnose possible inflammatory myopathy or to detect recurrences. PLACE OF DEVELOPMENT OF THE STUDY: Public Health Service of São Paulo State. PARTICIPANTS: children with clinical features of inflammatory myopathy. INTERVENTION: biopsies were performed on the vastus lateralis using local anesthetic. Histochemistry was performed according to standardized methods. RESULTS: Architectural changes of the muscle fibers, necrosis of variable intensity and accentuated evidence of regeneration were observed in patients who had not received treatment (2 cases) and in one case where muscular weakness persisted in spite of corticosteroid therapy. Necrosis and regeneration were minimal or absent in cases treated for one year or more (4 cases). In 3 cases with clinical and laboratorial recurrences, muscle necrosis and architectural changes were detected. CONCLUSIONS: It was concluded that muscle biopsy could aid in diagnosing infantile dermatomyositis as well as in detecting recurrences even in cases without clinical activity of the disease.

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Hand Muscle Pathology after Long-Term Vibration Exposure

Journal of Hand Surgery (European Volume) ◽

10.1016/j.jhsb.2004.05.004 ◽

2004 ◽

Vol 29 (5) ◽

pp. 431-437 ◽

Cited By ~ 19

Author(s):

LARS E. NECKING ◽

GÖRAN LUNDBORG ◽

RONNIE LUNDSTRÖM ◽

LARS-ERIC THORNELL ◽

JAN FRIDÉN

Keyword(s):

Morphological Changes ◽

Motor Nerve ◽

Muscle Pathology ◽

Muscle Fibres ◽

Vibration Exposure ◽

Vibration Syndrome ◽

Abductor Pollicis Brevis ◽

Hand Muscle ◽

Muscle Biopsies

The morphology of the abductor pollicis brevis muscle was studied in 20 patients suffering from hand–arm vibration syndrome. The main morphological changes observed were centrally located myonuclei and fibre type grouping (found in all 20 muscle biopsies), angulated muscle fibres (found in 19 biopsies), ring fibres and regenerating fibres (found in 18 biopsies) and fibrosis (found in 17 biopsies). The observed abnormalities are believed to reflect damage to both the muscle fibres and the motor nerve. The changes were related to different vibration exposure parameters. The number of fibres demonstrating centrally located nuclei correlated significantly with the cumulative vibration exposure, while the number of angulated fibres correlated significantly with the total vibration exposure time. This indicates that the vibrating tools may cause direct damage to muscle fibres as well as nerves.

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G.P.5.01 Inflammatory or ‘congenital myopathy’ type findings in muscle biopsies of patients with LMNA mutations

Neuromuscular Disorders ◽

10.1016/j.nmd.2007.06.124 ◽

2007 ◽

Vol 17 (9-10) ◽

pp. 797 ◽

Cited By ~ 2

Author(s):

F. Lubieniecki ◽

S. Monges ◽

A. Dubrovsky ◽

A. Stewart-Harris ◽

V. Ruggieri ◽

...

Keyword(s):

Congenital Myopathy ◽

Muscle Biopsies

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Expanding the Phenotypic Spectrum of ECEL1-Associated Distal Arthrogryposis

Children ◽

10.3390/children8100909 ◽

2021 ◽

Vol 8 (10) ◽

pp. 909

Author(s):

Akshata Huddar ◽

Kiran Polavarapu ◽

Veeramani Preethish-Kumar ◽

Mainak Bardhan ◽

Gopikrishnan Unnikrishnan ◽

...

Keyword(s):

Motor Development ◽

Fatty Infiltration ◽

Birth Asphyxia ◽

Lower Limbs ◽

Mild Intellectual Disability ◽

Abductor Pollicis Brevis ◽

Limb Weakness ◽

Muscle Mri ◽

Distal Arthrogryposis ◽

Exon 2

Distal arthrogryposis type 5D (DA5D), a rare autosomal recessive disorder, is caused by mutations in ECEL1. We describe two consanguineous families (three patients) with novel ECEL1 gene mutations detected by next-generation sequencing (NGS). A 12-year-old boy (patient 1) presented with birth asphyxia, motor developmental delay, multiple joint contractures, pes planus, kyphoscoliosis, undescended testis, hypophonic speech with a nasal twang, asymmetric ptosis, facial weakness, absent abductor pollicis brevis, bifacial, and distal lower limb weakness. Muscle MRI revealed asymmetric fatty infiltration of tensor fascia lata, hamstring, lateral compartment of the leg, and gastrocnemius. In addition, 17-year-old monozygotic twins (patients 2 and 3) presented with motor development delay, white hairlock, hypertelorism, tented upper lip, bulbous nose, tongue furrowing, small low set ears, multiple contractures, pes cavus, prominent hyperextensibility at the knee, hypotonia of lower limbs, wasting and weakness of all limbs (distal > proximal), areflexia, and high steppage gait. One had perinatal insult, seizures, mild intellectual disability, unconjugated eye movements, and primary optic atrophy. In the twins, MRI revealed extensive fatty infiltration of the gluteus maximus, quadriceps, hamstrings, and anterior and posterior compartment of the leg. Electrophysiology showed prominent motor axonopathy. NGS revealed rare homozygous missense variants c.602T > C (p.Met201Thr) in patient 1 and c.83C > T (p.Ala28Val) in patients 2 and 3, both localized in exon 2 of ECEL1 gene. Our three cases expand the clinical, imaging, and molecular spectrum of the ECEL1-mutation-related DA5D.

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