Common recessive limb girdle muscular dystrophies differential diagnosis: why and how?

Abstract

Limb girdle muscular dystrophies are heterogeneous autosomal hereditary neuromuscular disorders. They produce dystrophic changes on muscle biopsy and they are associated with mutations in several genes involved in muscular structure and function. Detailed clinical, laboratorial, imaging, diagnostic flowchart, photographs, tables, and illustrated diagrams are presented for the differential diagnosis of common autosomal recessive limb girdle muscular dystrophy subtypes diagnosed nowadays at one reference center in Brazil. Preoperative image studies guide muscle biopsy site selection. Muscle involvement image pattern differs depending on the limb girdle muscular dystrophy subtype. Muscle involvement is conspicuous at the posterior thigh in calpainopathy and fukutin-related proteinopathy; anterior thigh in sarcoglycanopathy; whole thigh in dysferlinopathy, and telethoninopathy. The precise differential diagnosis of limb girdle muscular dystrophies is important for genetic counseling, prognostic orientation, cardiac and respiratory management. Besides that, it may probably, in the future, provide specific genetic therapies for each subtype.Keywords: muscular dystrophies, ultrasonography, biopsy, magnetic resonance imaging, neuromuscular diseases. RESUMOAs distrofias musculares progressivas cintura-membros são desordens neuromusculares hereditárias autossômicas heterogêneas. Elas produzem alterações distróficas à biópsia muscular e estão associadas a mutações em diversos genes envolvidos na estrutura e função muscular. Fluxograma diagnóstico, fotos, tabelas e diagramas ilustrados dos aspectos clínicos, laboratoriais e de imagem são apresentados para o diagnóstico diferencial de distrofias musculares cintura-membros autossômicas recessivas comuns, diagnosticadas atualmente em um centro de referência no Brasil. Exames de imagem pré-operatórios direcionam o local da biópsia muscular. O padrão de envolvimento muscular difere de acordo com o subtipo de distrofia muscular cintura-membros. A substituição fibroadiposa do tecido muscular é mais acentuada no compartimento posterior da coxa na calpainopatia e proteinopatia relacionada à fukutina; anterior da coxa na sarcoglicanopatia; difusa na coxa na disferlinopatia e teletoninopatia. O diagnóstico diferencial preciso das distrofias musculares cintura-membros é importante para o aconselhamento genético, orientação prognóstica, tratamento cardíaco e respiratório. Além disso poderá, no futuro, provavelmente, propiciar terapias gênicas específicas para cada subtipo.Palavras-chave: distrofias musculares, ultrassonografia, biópsia, imagem por ressonância magnética, doenças neuromusculares.

Advanced MRI Patterns of Muscle Disease in Inherited and Acquired Myopathies: What the Radiologist Should Know

“…General or focal increase in muscle volume may be found in some inherited myopathies. Focal hypertrophy is described in infantile Pompe's disease (metabolic myopathy), sarcoglycanopathies (limb-girdle muscular dystrophy [LGMD] types 2C-F), and dystroglycanopathies (congenital muscular dystrophies), 1,35 among others (►Fig. 2h).…”

“…MRI is useful to distinguish these conditions from late-onset acid maltase deficiency (late-onset Pompe's disease), occasionally presenting as a phenocopy of recessive LGMD but showing unusually severe and early adductor involvement. 33,35,54,66 Facioscapulohumeral Dystrophy FSHD is the third most common muscular dystrophy, after DMD and MD, and the most prevalent muscular dystrophy (7:100,000). 68,69 In most patients (95%), it is inherited as an autosomal dominant trait, caused by a contracted D4Z4 microsatellite array on the subtelomeric region of chromosome 4q, associated with DUX4 gene encoding.…”

Pathology of Adult and Paediatric Mitochondrial Myopathies

“…Similar changes may be seen in skeletal muscle in the context of ageing, and in a range of genetic and acquired disorders. These include infantile Pompe disease and adult-onset acid maltase deficiency 15 , occasionally in muscular dystrophies such as LGMD2A 134 and FSHD 135 rarely primary lipid storage myopathies 113 . Muscle biopsies of patients with inclusion body myositis (IBM) may show increased numbers of RRF and COX-negative fibres 136 .…”

Diagnosis of limb-girdle muscular dystrophies in the molecular biology era: do clinical findings still matter?

“…Each type of dystrophy affects a specific muscle group, and the type of genetic testing requested depends on the muscle group affected. Knowledge of the affected muscles also helps to choose the muscle to be biopsied when molecular biology tests are inconclusive 9 . However, genetic testing and muscle biopsies are still very expensive and not widely available in Brazil or other countries.…”