Challenging Neuromuscular Disease Cases

Abstract

The diagnosis of neuromuscular disorders requires a thorough history including family history and examination, with the next steps broadened now beyond electromyography and neuropathology to include genetic testing. The challenge in diagnosis can often be putting all the information together. With advances in genetic testing, some diagnoses that adult patients may have received as children deserve a second look and may result in diagnoses better defined or alternative diagnoses made. Clearly defining or redefining a diagnosis can result in understanding of potential other systems involved, prognosis, or potential treatments. This article presents several cases and approach to diagnosis as well as potential treatment and prognostic concerns, including seipinopathy, congenital myasthenic syndrome, central core myopathy, and myotonic dystrophy type 2.

Keywords

myopathy - congenital myasthenic syndrome - myotonic dystrophy - seipinopathy

Publication History

Accepted Manuscript online:
23 November 2022

Article published online:
29 December 2022

• References

• 1 Ito D, Suzuki N. Seipinopathy: a novel endoplasmic reticulum stress-associated disease. Brain 2009; 132 (Pt 1): 8-15
• 2 Rickman OJ, Baple EL, Crosby AH. Lipid metabolic pathways converge in motor neuron degenerative diseases. Brain 2020; 143 (04) 1073-1087
• 3 Choudhary V, Schneiter R. A unique junctional interface at contact sites between the endoplasmic reticulum and lipid droplets. Front Cell Dev Biol 2021; 9: 650186
• 4 Ito D. BSCL2-Related Neurologic Disorders/Seipinopathy. GeneReviews® Internet. 2005 Accessed October 31, 2021 at: https://pubmed.ncbi.nlm.nih.gov/20301484/
• 5 Windpassinger C, Auer-Grumbach M, Irobi J. et al. Heterozygous missense mutations in BSCL2 are associated with distal hereditary motor neuropathy and Silver syndrome. Nat Genet 2004; 36 (03) 271-276
• 6 Auer-Grumbach M, Schlotter-Weigel B, Lochmüller H. et al; Austrian Peripheral Neuropathy Study Group. Phenotypes of the N88S Berardinelli-Seip congenital lipodystrophy 2 mutation. Ann Neurol 2005; 57 (03) 415-424
• 7 Irobi J, Van den Bergh P, Merlini L. et al. The phenotype of motor neuropathies associated with BSCL2 mutations is broader than Silver syndrome and distal HMN type V. Brain 2004; 127 (Pt 9): 2124-2130
• 8 Berardinelli W. An undiagnosed endocrinometabolic syndrome: report of 2 cases. J Clin Endocrinol Metab 1954; 14 (02) 193-204
• 9 Seip M. Lipodystrophy and gigantism with associated endocrine manifestations. A new diencephalic syndrome?. Acta Paediatr (Stockh) 1959; 48: 555-574
• 10 Winder TL, Tan CA, Klemm S. et al. Clinical utility of multigene analysis in over 25,000 patients with neuromuscular disorders. Neurol Genet 2020; 6 (02) e412
• 11 North K. Congenital myopathies. In: Engel AG, Franzini-Armstrong C, eds. Myology: Basic and Clinical. 3rd ed. New York, NY: McGraw-Hill; 2004: 1502-1503
• 12 Bartholomeus MG, Gabreëls FJ, ter Laak HJ, van Engelen BG. Congenital fibre type disproportion a time-locked diagnosis: a clinical and morphological follow-up study. Clin Neurol Neurosurg 2000; 102 (02) 97-101
• 13 Sobrido MJ, Fernández JM, Fontoira E. et al. Autosomal dominant congenital fibre type disproportion: a clinicopathological and imaging study of a large family. Brain 2005; 128 (Pt 7): 1716-1727
• 14 Engel AG, Ohno K, Sine SM. Congenital myasthenic syndromes. In: Engel AG, Franzini-Armstrong C, eds. Myology: Basic and Clinical. 3rd ed. New York, NY: McGraw-Hill; 2004: 1833-1835
• 15 Burke G, Cossins J, Maxwell S. et al. Rapsyn mutations in hereditary myasthenia: distinct early- and late-onset phenotypes. Neurology 2003; 61 (06) 826-828
• 16 Engel AG, Shen XM, Selcen D, Sine SM. Congenital myasthenic syndromes: pathogenesis, diagnosis, and treatment. Lancet Neurol 2015; 14 (04) 420-434
• 17 Dlamini N, Voermans NC, Lillis S. et al. Mutations in RYR1 are a common cause of exertional myalgia and rhabdomyolysis. Neuromuscul Disord 2013; 23 (07) 540-548
• 18 Klein A, Lillis S, Munteanu I. et al. Clinical and genetic findings in a large cohort of patients with ryanodine receptor 1 gene-associated myopathies. Hum Mutat 2012; 33 (06) 981-988
• 19 Wu S, Ibarra MC, Malicdan MC. et al. Central core disease is due to RYR1 mutations in more than 90% of patients. Brain 2006; 129 (Pt 6): 1470-1480
• 20 Robinson R, Carpenter D, Shaw MA, Halsall J, Hopkins P. Mutations in RYR1 in malignant hyperthermia and central core disease. Hum Mutat 2006; 27 (10) 977-989
• 21 Hopkins PM, Rüffert H, Snoeck MM. et al; European Malignant Hyperthermia Group. European Malignant Hyperthermia Group guidelines for investigation of malignant hyperthermia susceptibility. Br J Anaesth 2015; 115 (04) 531-539
• 22 Paganoni S, Amato A. Electrodiagnostic evaluation of myopathies. Phys Med Rehabil Clin N Am 2013; 24 (01) 193-207
• 23 Meola G. Myotonic dystrophy type 2: the 2020 update. Acta Myol 2020; 39 (04) 222-234
• 24 Liquori CL, Ricker K, Moseley ML. et al. Myotonic dystrophy type 2 caused by a CCTG expansion in intron 1 of ZNF9. Science 2001; 293 (5531): 864-867
• 25 Thornton CA, Griggs RC, Moxley III RT. Myotonic dystrophy with no trinucleotide repeat expansion. Ann Neurol 1994; 35 (03) 269-272
• 26 Schoser BG, Schneider-Gold C, Kress W. et al. Muscle pathology in 57 patients with myotonic dystrophy type 2. Muscle Nerve 2004; 29 (02) 275-281
• 27 Schoser B, Montagnese F, Bassez G. et al; Myotonic Dystrophy Foundation. Consensus-based care recommendations for adults with myotonic dystrophy type 2. Neurol Clin Pract 2019; 9 (04) 343-353