Unique Clinical, Radiological and Histopathological Characteristics of a Southeast Asian Cohort of Patients with Limb-Girdle Muscular Dystrophy 2G/LGMD-R7-Telethonin-Related

Article type: Research Article

Authors: Chen, Zhiyong^{a; *} | Saini, Monica^a | Koh, Jasmine S.^a | Prasad, Kalpana^a | Koh, Swee Hoon^b | Tay, Karine S.S.^b | Lee, Ming^c | Tan, Yi Jayne^a | Ng, Adeline S.L.^{a; d} | Tay, Stacey Kiat Hong^{e; f} | Tan, Kong Bing^g | Tandon, Ankit^h | Tan, Jeane M.M.^a | Chai, Josiah Y.H.^{a; b}

Affiliations: [a] Department of Neurology, National Neuroscience Institute, Singapore | [b] Neuromuscular Laboratory, National Neuroscience Institute, Singapore | [c] Department of Pathology, Singapore General Hospital, Singapore | [d] Duke NUS Graduate Medical School, Singapore | [e] Department of Paediatrics, Khoo Teck Puat-National University Children’s Medical Institute, National University Health System, Singapore | [f] Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore | [g] Department of Pathology, National University Hospital, Singapore | [h] Department of Diagnostic Radiology, Tan Tock Seng Hospital, Singapore

Correspondence: [*] Correspondence to: Z. Chen, Department of Neurology, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore. Tel.: +65 63577171; Fax: +65 63577137; E-mail: [email protected].

Abstract: Aim:We describe a cohort of five patients with limb-girdle muscular dystrophy (LGMD) 2G/LGMD-R7 in a South-east Asian cohort. Background:LGMD2G/LGMD-R7-telethonin-related is caused by mutations in the TCAP gene that encodes for telethonin. Methods:We identified consecutive patients with LGMD2G/LGMD-R7-telethonin-related, diagnosed at the National Neuroscience Institute (NNI) and National University Hospital (NUH) between January 2000 and June 2021. Results:At onset, three patients presented with proximal lower limb weakness, one patient presented with Achilles tendon contractures, and one patient presented with delayed gross motor milestones. At last follow up, three patients had a limb girdle pattern of muscle weakness and two had a facioscapular humeral pattern of weakness. Whole body muscle MRI performed for one patient with a facioscapular-humeral pattern of weakness showed a pattern of muscle atrophy similar to facioscapular-humeral dystrophy. One patient had histological features consistent with myofibrillar myopathy; electron microscopy confirmed the disruption of myofibrillar architecture. One patients also had reduced staining to telethonin antibody on immunohistochemistry. Conclusion:We report the unique clinical and histological features of a Southeast Asian cohort of five patients with LGMD2G/LGMD-R7-telethonin-related muscular dystrophy and further expand its clinical and histopathological spectrum.

Keywords: Telethonin deficiency, LGMD2G, TCAP, muscular dystrophy

DOI: 10.3233/JND-221517

Journal: Journal of Neuromuscular Diseases, vol. 10, no. 1, pp. 91-106, 2023