P.15 Symptomatic DMD carrier as a differential diagnosis in patients presenting asymmetrical limb weakness

Abstract

Duchenne/Becker muscular dystrophy (DMD) is one of the most common myopathies, characterized by an X-linked recessive disease. Asymmetrical limb weakness is rarely present in patients with muscle diseases such as ANO5-related myopathy, facioscapulohumeral muscular dystrophy, and sporadic inclusion body myositis. We report two cases of symptomatic DMD carriers presenting with asymmetrical limb weakness. A 50-year-old woman visited the department of neurology presenting with slowly progressive weakness of the limbs since childhood. A neurological examination revealed a weakness of the right arm and both legs, which were graded 4 as MRC system. Muscle MRI showed asymmetric fatty infiltration of the limbs, markedly affected by right biceps brachii, latissimus dorsi, and gastrocnemius. Immunohistochemistry (IHC) of the C-terminal region of the dystrophin gene presented several scattered stain-negative fibers. Genetic analysis revealed c.6703delG (p.Ser2235Ilefs*12, NM_004006.2) mimicking single exon 46 deletion in MLPA. A 29-year-old female presented with an elevated level of serum creatine kinase without subjective weakness. Neurologic examination showed the subtle motor weakness of the right arm, graded 4+. Muscle MRI revealed high T1 signal change on the right biceps femoris, which was not affected clinically, in addition to right biceps brachii and latissimus dorsi. IHC showed dystrophic changes and a mosaic pattern of dystrophin expression. The diagnosis was confirmed by MLPA, revealing heterozygous deletion of exon 44 in the DMD gene. Asymmetrical limb weakness can be a remark for the diagnosis of symptomatic DMD carrier. Furthermore, muscle MRI is more sensitive in detecting pathologic changes than routine neurologic examination. And single-base point mutation can mimick the exon deletion in MLPA, which needs sequencing analysis in a case of single exon deletion in DMD. Therefore, a multidisciplinary approach is mandatory for final diagnosis and a better understanding of symptomatic DMD carriers.