Limb girdle muscular dystrophies: clinical-genetical diagnostic update and prospects for therapy

ABSTRACT

Introduction: Limb Girdle Muscular Dystrophies (LGMD) are a clinically heterogeneous group of disorders presenting with a spectrum of disease severity ranging from severe childhood onset muscular dystrophy to adult-onset dystrophy. LGMDs include both dominant and recessive forms.

Areas covered: The clinical phenotypes and diagnostic features of LGMD and specific features for each disease have been presented. An updated list of molecularly defined LGMD is provided. The instrumental, muscle imaging, and laboratory exams commonly used to assess final diagnosis are described, as well as recent genetic techniques and new diagnostic procedures, i.e. next generation sequencing, whole exome sequencing, RNA sequencing as compared to other techniques (e.g. protein analysis). The clinical management of patients and their main clinical respiratory and cardiac complications is covered. We also focus on current available future drugs or gene therapy and management by rehabilitation.

Expert opinion: Many LGMD cases, who in the past remained for long time without a molecular diagnosis, nowadays can be investigated by next generation sequencing. Gene mutation analysis is always required to obtain a molecular diagnosis, and is fundamental to select patients for future pharmacological trials and gene therapies.

KEYWORDS:

• Limb girdle muscular dystrophy
• LGMD
• diagnosis
• treatment

Article highlights

• An additional 20% of LGMD cases can be diagnosed by next generation sequencing

• Better genetic diagnosis allows genetic counselling

• Clinical phenotyping and clinical studies are producing data to build pivotal aspects of clinical outcome for possible trials that should include disorders with common pathogeneses

• Standardized phenotypes such as ‘Phenotips’ could identify patients with undiagnosed LGMD phenotypes.

• For treatment, a personalized rehabilitation program has to be established in LGMD patients to reduce joint contractures and improve respiratory insufficiency.

This box summarizes 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.

Additional information

Funding

This paper was funded by TELETHON GUP 13012, GGP14066, EUROBIOBANK, BBMRNR.