Making sense of the clinical spectrum of limb girdle muscular dystrophies

Abstract

The expansion of the spectrum of limb girdle muscular dystrophies (LGMDs) in recent years means that neurologists need to be familiar with the clinical clues that can help with their diagnosis. The LGMDs comprise a group of genetic myopathies that manifest as chronic progressive weakness of hip and shoulder girdles. Their inheritance is either autosomal dominant (LGMD1) or autosomal recessive (LGMD2). Their prevalence varies in different regions of the world; certain ethnic groups have documented founder mutations and this knowledge can facilitate the diagnosis. The clinical approach to LGMDs uses the age at onset, genetic transmission and clinical patterns of muscular weakness. Helpful clinical features that help to differentiate the various subtypes include: predominant upper girdle weakness, disproportionate respiratory muscle involvement, distal weakness, hip adductor weakness, 'biceps lump' and 'diamond on quadriceps' sign, calf hypertrophy, contractures and cardiac involvement. Almost half of patients with LGMD have such clinical clues. Investigations such as serum creatine kinase, electrophysiology, muscle biopsy and genetic studies can complement the clinical examination. In this review, we discuss diagnostic clinical pointers and comment on the differential diagnosis and relevant investigations, using illustrative case studies.

Circulating Biomarkers in Muscular Dystrophies: Disease and Therapy Monitoring

“…LGMDs usually cause weakness and wasting of the proximal muscles, including the muscles of the arms and legs. 62 Regarding the development of biomarkers, work was performed on specific types of LGMDs, including LGMD2A, LGMD2B, LGMD2C, and LGMD2D. Due to the high heterogeneity and the increase in the characterization of new diseases in the family of LGMDs, a consortium was recently assigned to suggest an improved classification system for this large heterogeneous group of diseases.…”

Limb Girdle Muskuler Distrofi Tip 2a: Vaka Sunumu

“…The recessive forms also can be divided at molecular level as sarcoglycanopathies and non-sarcoglycanopathies based on the affected mutation in a gene encoding sarcoglycan component of the dystrophin associated complex or not. LGMD 2A is in the group of nonsarcoglycanopathy and known as calpainopathy (2). There is the defect of gene encoding the protein named as calpain and has autosomal recessive inheritance pattern in LGMD 2A.…”

Muscle biopsy: what and why and when?

“…There are many clues to help to distinguish between an acquired myopathy and genetic disorder, see further reading. 3 5–7…”

“…Generally, in a patient with a likely genetic cause for limb-girdle weakness, especially with pseudohypertrophy and raised serum creatine kinase, we request a dried blood spot test for α-glucosidase, and genetic testing for dystrophinopathy and LGMD2I, before a muscle biopsy. 5 6 8 The clinical rules distinguishing genetic and acquired myopathies are robust but fallible, one reason to favour biopsy at this point.…”