Abstract
BackgroundLimb-girdle muscular dystrophy (LGMD) is a commonly diagnosed hereditary muscular disorder, characterized by the progressive weakness of the limb-girdle muscles. Although the condition has been well-characterized, clinical and genetic heterogeneity can be observed in patients with LGMD. Here, we aimed to describe the clinical manifestations and genetic variability among a cohort of patients with LGMD in South China.ResultsWe analyzed the clinical information, muscle magnetic resonance imaging (MRI) findings, and genetic results obtained from 30 patients (24 families) with clinically suspected LGMD. In 24 probands, 38 variants were found in total, of which 18 were shown to be novel. Among the 30 patients, the most common subtypes were dysferlinopathy in eight (26.67%), sarcoglycanopathies in eight [26.67%; LGMD 2C in three (10.00%), LGMD 2D in three (10.00%), and LGMD 2F in two (6.67%)], LGMD 2A in seven (23.33%), followed by LGMD 1B in three (10.00%), LGMD 2I in three (10.00%), and early onset recessive Emery-Dreifuss-like phenotype without cardiomyopathy in one (3.33%). Furthermore, we also observed novel clinical presentations for LGMD 1B, 2F, and 2I patients with hypermobility of the joints in the upper limbs, a LGMD 2F patient with delayed language development, and other manifestations. Moreover, distinct distributions of fatty infiltration in patients with LGMD 2A, dysferlinopathy, and the early onset recessive Emery-Dreifuss-like phenotype without cardiomyopathy were also observed based on muscle MRI results.ConclusionsIn this study, we expanded the clinical spectrum and genetic variability found in patients with LGMD, which provided additional insights into genotype and phenotype correlations in this disease.
Highlights
Limb-girdle muscular dystrophy (LGMD) is a commonly diagnosed hereditary muscular disorder, characterized by the progressive weakness of the limb-girdle muscles
The most frequent subtypes were dysferlinopathy [seven probands (29.17% of probands), eight patients (26.67% of patients)], sarcoglycanopathies [LGMD 2C-F; seven probands (29.17% of probands), eight patients (26.67% of patients)], LGMD 2A [four probands (16.67% of probands), seven patients (23.33% of patients)], and LGMD 1B [three probands (12.50% of probands); three patients (10.00% of patients)]
When analyzing predominant involvements of proximal or distal limbs, the results indicated that most probands were characterized by predominant weakness of the scapular and/or pelvic muscles (83.33%); three probands were characterized by predominant weakness of the distal lower limbs and one proband, with dysferlinopathy characterized by mild weakness of both proximal and distal lower limbs
Summary
Limb-girdle muscular dystrophy (LGMD) is a commonly diagnosed hereditary muscular disorder, characterized by the progressive weakness of the limb-girdle muscles. Considering the genetic and phenotypic heterogeneity of this disease, LGMD should be considered in almost all undiagnosed patients complaining of primary muscle weakness [10]. Certain clinical features of LGMD subtypes can serve as valuable diagnostic clues, such as extremely high levels of serum creatine kinase (CK) in LGMD 2B-F and LGMD 2I patients [11]. Other approaches such as muscle biopsy and muscle magnetic resonance imaging (MRI) may help establish the clinical diagnosis [12, 13]. A comprehensive understanding of the genetic variability and clinical spectrum of LGMD is essential before precise diagnosis, treatment and reproductive counselling can be offered [2]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
