Distinct and Recognisable Muscle MRI Pattern in a Series of Adults Harbouring an Identical GMPPB Gene Mutation

Article type: Research Article

Authors: Siddiqui, Shahyan^a | Polavarapu, Kiran^{b; d} | Bardhan, Mainak^b | Preethish-Kumar, Veeramani^b | Joshi, Aditi^c | Nashi, Saraswati^b | Vengalil, Seena^b | Raju, Sanita^b | Chawla, Tanushree^b | Leena, Shingavi^b | Mathur, Aradhana^c | Nayak, Sushmita^c | Mohan, Dhaarini^b | Shamim, Uzma^c | Prasad, Chandrajit^a | Lochmüller, Hanns^d | Faruq, Mohammed^c | Nalini, Atchayaram^{b; *}

Affiliations: [a] Department of Neuroimaging and Interventional radiology, National Institute of Mental Health and Neurosciences, Bengaluru, India | [b] Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, India | [c] Genomics and Molecular Medicine, CSIR-Institute of Genomics and Integrative Biology, New Delhi, India | [d] Children’s Hospital of Eastern Ontario Research Institute; Division of Neurology, Department of Medicine, The Ottawa Hospital; Brain and Mind Research Institute, University of Ottawa, Ottawa, ON, Canada

Correspondence: [*] Correspondence to: Atchayaram Nalini, Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, India. E-mail: [email protected].

Abstract: Background and Purpose:Mutations in the GMPPB gene affect glycosylation of α-dystroglycan, leading to varied clinical phenotypes. We attempted to delineate the muscle MR imaging spectrum of GMPPB-related Congenital Myasthenic syndrome (CMS) in a single-center cohort study. Objective:To identify the distinct patterns of muscle involvement in GMPPB gene mutations. Methods:We analyzed the muscle MR images of 7 genetically proven cases of GMPPB dystroglycanopathy belonging to three families and studied the potential qualitative imaging pattern to aid in clinico -radiological diagnosis in neuromuscular practice. All individuals underwent muscle MRI (T1, T2, STIR/PD Fat sat. sequences in 1.5 T machine) of the lower limbs. Qualitative assessment and scoring were done for muscle changes using Mercuri staging for fibro-fatty replacement on T1 sequence and Borsato score for myoedema on STIR sequence. Results:All patients were of South Indian origin and presented as slowly progressive childhood to adult-onset fatigable limb-girdle muscle weakness, elevated creatine kinase level, and positive decrement response in proximal muscles. Muscle biopsy revealed features of dystrophy. All patients demonstrated identical homozygous mutation c.1000G > A in the GMPPB gene. MRI demonstrated early and severe involvement of paraspinal muscles, gluteus minimus, and relatively less severe involvement of the short head of the biceps femoris. A distinct proximo-distal gradient of affliction was identified in the glutei, vasti, tibialis anterior and peronei. Also, a postero-anterior gradient was observed in the gracilis muscle. Conclusion:Hitherto unreported, the distinctive MR imaging pattern described here, coupled with relatively slowly progressive symptoms of fatigable limb-girdle weakness, would facilitate an early diagnosis of the milder form of GMPPB- dystroglycanopathy associated with homozygous GMPPB gene mutation.

Keywords: GMPPB, congenital myasthenic syndrome, limb-girdle muscular dystrophy, magnetic resonance imaging

DOI: 10.3233/JND-200628

Journal: Journal of Neuromuscular Diseases, vol. 9, no. 1, pp. 95-109, 2022