A study of the phenotypic variability and disease progression in Laing myopathy through the evaluation of muscle imaging

Abstract

Background Laing myopathy is characterized by broad clinical and pathological variability. They are limited in number and protocol of study. We aimed to delineate muscle imaging profiles and validate imaging analysis as an outcome measure. Methods This was a cross‐sectional and longitudinal cohort study. Data from clinical, functional and semi‐quantitative muscle imaging (60 magnetic resonance imaging [MRI] and six computed tomography scans) were studied. Hierarchical analysis, graphic heatmap representation and correlation between imaging and clinical data using Bayesian statistics were carried out. Results The study cohort comprised 42 patients from 13 families harbouring five MYH7 mutations. The cohort had a wide range of ages, age at onset, disease duration, and myopathy extension and Gardner‐Medwin and Walton (GMW) functional scores. Intramuscular fat was evident in all but two asymptomatic/pauci‐symptomatic patients. Anterior leg compartment muscles were the only affected muscles in 12% of the patients. Widespread extension to the thigh, hip, paravertebral and calf muscles and, less frequently, the scapulohumeral muscles was commonly observed, depicting distinct patterns and rates of progression. Foot muscles were involved in 40% of patients, evolving in parallel to other regions with absence of a disto‐proximal gradient. Whole cumulative imaging score, ranging from 0 to 2.9 out of 4, was associated with disease duration and with myopathy extension and GMW scales. Follow‐up MRI studies in 24 patients showed significant score progression at a variable rate. Conclusions We confirmed that the anterior leg compartment is systematically affected in Laing myopathy and may represent the only manifestation of this disorder. However, widespread muscle involvement in preferential but variable and not distance‐dependent patterns was frequently observed. Imaging score analysis is useful to categorize patients and to follow disease progression over time.

Muscle magnetic resonance imaging involvement patterns in nemaline myopathies

“…46 However, Laing myopathy patients may also demonstrate an inverted or true collagen VI sign which is absent in NEB-NM and was not seen in any of our patients. 46 We also noted a similarity in the pattern of muscle involvement between RYR1-related congenital myopathy and the TPM3-NM group presented here. In particular, we demonstrated relative sparing of the rectus femoris, comparative lesser involvement of the adductor longus compared to the adductor magnus, involvement of the sartorius, comparative sparing of the gracilis and notable involvement of the soleus in the lower leg; findings that are similar to those observed in RYR1 congenital myopathy (Fig.…”

“…3 and 4) and those commonly associated with other congenital myopathies and muscular dystrophies 7,45 . One exception is the isolated distal lower limb involvement, predominantly of the anterior compartment, seen in around 12% of patients with Laing distal myopathy due to pathogenic MYH7 gene variants, which may mimic the imaging findings seen in NEB ‐NM 46 . However, Laing myopathy patients may also demonstrate an inverted or true collagen VI sign which is absent in NEB ‐NM and was not seen in any of our patients 46 .…”

“…One exception is the isolated distal lower limb involvement, predominantly of the anterior compartment, seen in around 12% of patients with Laing distal myopathy due to pathogenic MYH7 gene variants, which may mimic the imaging findings seen in NEB ‐NM 46 . However, Laing myopathy patients may also demonstrate an inverted or true collagen VI sign which is absent in NEB ‐NM and was not seen in any of our patients 46 . We also noted a similarity in the pattern of muscle involvement between RYR1 ‐related congenital myopathy and the TPM3 ‐NM group presented here.…”

Charcot–Marie–Tooth disease due to MORC2 mutations in Spain

“…Muscle magnetic resonance imaging (MRI) was performed in the upper and lower limbs if possible. The protocol employed was the same as described previously, and muscle fatty substitution was graded from 0 to 4 according to the modified Mercuri score as follows: 0, no fat signal in muscle; 1, traces of increased signal intensity on the T1‐weighted MRI sequences; 2, increased T1‐weighted signal intensity with beginning confluence in less than 50% of the muscle; 3, increased T1‐weighted signal intensity with beginning confluence in more than 50% of the muscle; 4, entire muscle replaced by increased density of connective tissue and fat [20,21]. Heat maps of muscle fatty infiltration were developed.…”