Clinical features and a mutation with late onset of limb girdle muscular dystrophy 2B

Abstract

Objective and methodsDysferlin encoded by DYSF deficiency leads to two main phenotypes, limb girdle muscular dystrophy (LGMD) 2B and Miyoshi myopathy. To reveal in detail the mutational and clinical features of LGMD2B in Japan, we observed 40 Japanese patients in 36 families with LGMD2B in whom dysferlin mutations were confirmed.Results and conclusionsThree mutations (c.1566C>G, c.2997G>T and c.4497delT) were relatively more prevalent. The c.2997G>T mutation was associated with late onset, proximal dominant forms of dysferlinopathy, a high probability that muscle weakness started in an upper limb and lower serum creatine kinase (CK) levels. The clinical features of LGMD2B are as follows: (1) onset in the late teens or early adulthood, except patients homozygous for the c.2997G>T mutation; (2) lower limb weakness at onset; (3) distal change of lower limbs on muscle CT at an early stage; (4) impairment of lumbar erector spinal muscles on muscle CT at an early stage; (5) predominant involvement of proximal upper limbs; (6) preservation of function of the hands at late stage; (7) preservation of strength in neck muscles at late stage; (8) lack of facial weakness or dysphagia; (9) avoidance of scoliosis; (10) hyper-Ckaemia; (11) preservation of cardiac function; and (12) a tendency for respiratory function to decline with disease duration. It is important that the late onset phenotype is found with prevalent mutations.

Novel duplication mutation of the DYSF gene in a Pakistani family with Miyoshi Myopathy

“…These patients differed from those with dysferlinopathy by their later age of onset (usually after 30 years of age) and discreetly raised serum CK level 22. In the present study, the clinical phenotype of Miyoshi myopathy is consistent with already reported phenotypes 4,8…”

“…It clinically resembles other myopathies which involves the distal musculature, especially the muscles of lower legs 3. The mutations in the DYSF gene are a major cause of this disease 4. It differs from LGMD2B, in which the proximal part of muscles are affected although other characteristics such as age of onset, higher creatine kinase (CK) levels, progressive disease pattern, and dysmorphology of muscles have been found as well 5…”

“…DYSF mutations are dispersed throughout the gene, and more than 500 pathogenic nucleotide variants are documented in Leiden Muscular Dystrophy Database for dysferlinopathy, showing different effects on protein function 8. Among the 122 reported sequence variations in the DYSF, 10 duplications were reported in several families and sporadic cases so far causing Miyoshi myopathy phenotype 4,7-12…”

Miyoshi myopathy: diagnosis of a familial case of dysferlinopathy

“…У 20 из 25 японских пациентов с клиническим ди-агнозом ММ выявили 16 разных мутаций в гене DYSF, 10 из которых были новыми [12]. В своей работе K. Nguyen и соавт.…”

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

“…First symptoms usually begin in a narrow age range around 19 years old, with exceptional cases starting from birth to 58 years old 35,36,37 (Table 2). Different from other limb girdle muscular dystrophies, subacute presentation may occur in about 25% of the patients.…”