Assessing diagnosis and managing respiratory and cardiac complications of sarcoglycanopathy

ABSTRACT

Introduction: Sarcoglycanopathies (SG) are caused by a mutation in SGCA, SGCB, SGCG, or SGCD genes and present a wide spectrum of muscle involvement and wasting. The clinical phenotypes due to a mutation in the sarcoglycan genes include severe childhood-onset forms, proximal myopathies, pseudometabolic myopathies, myopathies with respiratory complication, and hyperCKemia syndromes. Dilated cardiomyopathy is more frequent and severe in LGMD2E/R4 and LGMD2F/R6.

Areas covered: In this paper, the authors review clinical, epidemiological evidence-based studies for better understanding the clinical signs, natural history and provide an update on current diagnostic and therapeutic options linked to the management of respiratory insufficiency present in 26% of the cases and cardiac complications present in 22% of the cases, as well as physiotherapy/rehabilitation and drug treatment. We also briefly over-view new treatments specific to genetic mutations and clinical trials on gene therapy. The papers covering the diagnosis and clinical respiratory care and cardiac complications of sarcoglycanopathies were reviewed in PubMed since the year 1997 and we chose to analyze those that covered series of patients, animal studies were only annotated when relevant to pathophysiology or advances in treatment.

Expert opinion: Accurate molecular diagnosis of sarcoglycanopathy patients is crucial in order to offer precise genetic counseling and clinical care, both to offer effective management and to prevent cardiac insufficiency. It is important both for an early treatment of dilated cardiomyopathy and to prevent severe respiratory complications in specific subgroups of patients.

KEYWORDS:

• Sarcoglycan
• limb-girdle muscular dystrophy
• cardiac complication
• respiratory involvement
• physiotherapy rehabilitation
• new genetic therapies
• treatments

Article highlights

• An accurate diagnosis and precise cardiorespiratory assessment have relevant importance at the psychological level for the patient and family but is not done in uniform way in different countries.

• The diagnostic process needs an integrated approach that starts clinically and followed by monitoring individual cases. NGS might allow a more rapid diagnosis.

• Accurate molecular diagnosis of sarcoglycanopathy patients is crucial to offer precise genetic counseling and clinical care for these patients, as the frequency of severe cardiorespiratory complications in specific subgroups of patients shows this is essential for effective management.

• Muscle imaging, although still rarely done in sarcoglycanopathy cases, might be a useful tool to evaluate disease progression and efficacy of clinical trials.

This box summarizes the key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was supported by the AFM-Telethon 22392 grant and Biobank BBMRNR, part of the BBMRI-ERIC network.