Asymmetrical scapular winging, bilateral facial muscle involvement and distal myopathy with normal CPK; unusual features in anti JO-I positive polymyositis

AbstractUsing deep phenotyping and high-throughput sequencing, we have identified a novel type of distal myopathy caused by mutations in the Small muscle protein X-linked (SMPX) gene. Four different missense mutations were identified in ten patients from nine families in five different countries, suggesting that this disease could be prevalent in other populations as well. Haplotype analysis of patients with similar ancestry revealed two different founder mutations in Southern Europe and France, indicating that the prevalence in these populations may be higher. In our study all patients presented with highly similar clinical features: adult-onset, usually distal more than proximal limb muscle weakness, slowly progressing over decades with preserved walking. Lower limb muscle imaging showed a characteristic pattern of muscle involvement and fatty degeneration. Histopathological and electron microscopic analysis of patient muscle biopsies revealed myopathic findings with rimmed vacuoles and the presence of sarcoplasmic inclusions, some with amyloid-like characteristics. In silico predictions and subsequent cell culture studies showed that the missense mutations increase aggregation propensity of the SMPX protein. In cell culture studies, overexpressed SMPX localized to stress granules and slowed down their clearance.

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Concentric muscle involvement in POLG -related distal myopathy

Neuromuscular Disorders ◽

10.1016/j.nmd.2017.03.001 ◽

2017 ◽

Vol 27 (5) ◽

pp. 500-501 ◽

Cited By ~ 1

Author(s):

Giorgio Tasca ◽

Mauro Monforte ◽

Claudia Nesti ◽

Filippo Maria Santorelli ◽

Gabriella Silvestri ◽

...

Keyword(s):

Distal Myopathy ◽

Muscle Involvement

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Rare Genetic Variant of Distal Myopathy with Posterior Leg and Anterior Hand Involvement: Case Report

The Open Neurology Journal ◽

10.2174/1874205x02014010093 ◽

2020 ◽

Vol 14 (1) ◽

pp. 93-94

Author(s):

Daifallah Almalki ◽

Abdulrahman Ali

Keyword(s):

Rare Variant ◽

Age At Onset ◽

Binding Domain ◽

Actin Binding ◽

Distal Myopathy ◽

Muscle Involvement ◽

Progressive Muscle Weakness ◽

Actin Binding Domain ◽

Hand Involvement ◽

Distal Myopathies

Distal myopathies are a heterogeneous group of genetic muscle disorders characterized by weakness of distal muscle groups of the upper and lower extremities. The various types of distal myopathies can be clinically differentiated based on age at onset, pattern of muscle involvement, disease severity, and the mode of inheritance. We described a case of slowly progressive muscle weakness that involved one of the patients’ hand and posterior leg muscles. Her genetic study showed a rare variant that likely contributed to distal myopathy with posterior leg and anterior hand involvement (distal actin-binding domain [ABD]-filaminopathy). The disease is due to mutations on the actin-binding domain of the FLNC gene that encodes filamin C. This variant has been described only in one Italian family. This rare variant will expand our knowledge about the rare phenotype of distal myopathy with posterior leg and anterior hand involvement.

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Out-of-Frame Mutations in ACTN2 Last Exon Cause a Dominant Distal Myopathy With Facial Weakness

Neurology Genetics ◽

10.1212/nxg.0000000000000619 ◽

2021 ◽

Vol 7 (5) ◽

pp. e619

Author(s):

Marco Savarese ◽

Anna Vihola ◽

Manu E. Jokela ◽

Sanna Pauliina Huovinen ◽

Simonetta Gerevini ◽

...

Keyword(s):

High Throughput Sequencing ◽

Molecular Genetic ◽

Genetic Diagnosis ◽

Shoulder Girdle ◽

Distal Myopathy ◽

Facial Weakness ◽

Muscle Mri ◽

Muscle Involvement ◽

Molecular Genetic Diagnosis ◽

Shoulder Girdle Muscles

Background and ObjectivesTo clinically, genetically, and histopathologically characterize patients presenting with an unusual combination of distal myopathy and facial weakness, without involvement of upper limb or shoulder girdle muscles.MethodsTwo families with a novel form of actininopathy were identified. Patients had been followed up over 10 years. Their molecular genetic diagnosis was not clear after extensive investigations, including analysis of candidate genes and FSHD1-related D4Z4 repeats.ResultsPatients shared a similar clinical phenotype and a common pattern of muscle involvement. They presented with a very slowly progressive myopathy involving anterior lower leg and facial muscles. Muscle MRI finding showed complete fat replacement of anterolateral compartment muscles of the lower legs with variable involvement of soleus and gastrocnemius but sparing thigh muscles. Muscle biopsy showed internalized nuclei, myofibrillar disorganization, and rimmed vacuoles. High-throughput sequencing identified in each proband a heterozygous single nucleotide deletion (c.2558del and c.2567del) in the last exon of the ACTN2 gene. The deletions are predicted to lead to a novel but unstructured slightly extended C-terminal amino acid sequence.DiscussionOur findings indicate an unusual form of actininopathy with specific molecular and clinical features. Actininopathy should be considered in the differential diagnosis of distal myopathy combined with facial weakness.

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Brachio-cervical inflammatory myopathy associated with systemic sclerosis. Case series and review of literature

Reumatismo ◽

10.4081/reumatismo.2021.1397 ◽

2021 ◽

Vol 73 (2) ◽

pp. 122-130

Author(s):

C.S.R. Araujo ◽

R. Miossi ◽

F.H.C. De Souza ◽

M.D. Costa ◽

A.M.S. Da Silva ◽

...

Keyword(s):

Systemic Sclerosis ◽

Inflammatory Myopathy ◽

Elevated Serum ◽

Case Series ◽

Response To Treatment ◽

Published Data ◽

Muscle Involvement ◽

Mhc I ◽

Scapular Winging ◽

Tertiary Center

This study was aimed at describing a case series of brachio-cervical inflammatory myopathy (BCIM) associated with systemic sclerosis (SSc), due to its rarity and limited coverage in published data. Another aim was to provide a literature review. We reported four cases of BCIM-SSc from our tertiary center. In addition, we researched the literature and found six articles featuring 17 patients who fit this phenotype. We pooled all cases and reported their features. Most patients were female and had limited SSc, and the median time of BCIM presentation was three years after SSc diagnosis. Asymmetric muscle involvement, scapular winging, dropped head, axial weakness, camptocormia, dysphagia, and dermatomyositis stigmas were common features. All patients had esophageal involvement. Most had positive antinuclear antibody results, a scleroderma pattern in their capillaroscopy images, elevated serum creatine phosphokinase, myopathic electrophysiology, and muscle involvement in magnetic resonance imaging. Muscle histopathological findings varied widely, but in general all showed the presence of lymphoid infiltrates, muscle atrophy, increased MHC-I expression, MAC deposits, vasculopathy, and muscle fiber necrosis. The response to immunosuppressive therapy was highly irregular. BCIM-SSc is a rare disorder that shares many similar phenotypes among the described cases, but has a highly heterogeneous response to treatment. At present, more data on the physiopathology, clinical features, and treatment is still needed.

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