Abstract This article reports two cases of childhood-onset nemaline myopathy diagnosed by muscle pathology and genetic diagnosis. The two patients had onset in early childhood, with muscle weakness as the first manifestation, as well as long disease duration and slow progression. Gomori staining and hematoxylin-eosin staining showed redstained rods in the sarcoplasmic cytoplasm and sarcolemma under a light microscope. Electron microscopy showed that the dense nemaline rods were located under the muscle fiber sarcolemma and parallel to the long axis of the muscle fibers, and some muscle fiber myofilaments were dissolved and necrotic. Gene testing found that one of the two patients had heterozygous mutation (c.1013A > C) in the ACTA1 gene, and the other had compound heterozygous mutation (c.18676C > T and c.9812C > A) in the NEB gene. The two mutations were more common in nemaline myopathy. Nemaline myopathy is a recessive or dominant inheritance myopathy, in which the nemaline rod in the cytoplasm of myocytes is a characteristic muscle pathological change. Pathological and genetic diagnosis is the gold standard for diagnosis of nemaline myopathy.
HUANG Kun,LUO Yi-En,LI Qiu-Xiang et al. Clinical, pathological and genetic studies of two cases of childhood-onset nemaline myopathy[J]. CJCP, 2018, 20(10): 804-808.
HUANG Kun,LUO Yi-En,LI Qiu-Xiang et al. Clinical, pathological and genetic studies of two cases of childhood-onset nemaline myopathy[J]. CJCP, 2018, 20(10): 804-808.
Shy GM, Engel WK, Somers JE, et al. Nemaline myopathy. A new congenital myopathy[J]. Brain, 1963, 86(4):793-810.
[2]
Schnitzler LJ, Schreckenbach T, Nadaj-Pakleza A, et al. Sporadic late-onset nemaline myopathy:clinico-pathological characteristics and review of 76 cases[J]. Orphanet J Rare Dis, 2017, 12(1):86.
[3]
Wallgren-Pettersson C, Laing NG. Report of the 70th ENMC International Workshop:nemaline myopathy, 11-13 June 1999, Naarden, The Netherlands[J]. Neuromuscul Disord, 2000, 10(4-5):299-306.
[4]
Monforte M, Primiano G, Silvestri G, et al. Sporadic late-onset nemaline myopathy:clinical, pathology and imaging findings in a single center cohort[J]. J Neurol, 2018, 265(3):542-551.
[5]
Lee JM, Lim JG, Shin JH, et al. Clinical and genetic diversity of nemaline myopathy from a single neuromuscular center in Korea[J]. J Neurol Sci, 2017, 383:61-68.
[6]
Joureau B, de Winter JM, Conijn S, et al. Dysfunctional sarcomere contractility contributes to muscle weakness in ACTA1-related nemaline myopathy (NEM3)[J]. Ann Neurol, 2018, 83(2):269-282.
[7]
Malfatti E, Schaeffer U, Chapon F, et al. Combined cap disease and nemaline myopathy in the same patient caused by an autosomal dominant mutation in the TPM3 gene[J]. Neuromuscul Disord, 2013, 23(12):992-997.
[8]
Mroczek M, Kabzinska D, Chrzanowska KH, et al. A novel TPM2 gene splice-site mutation causes severe congenital myopathy with arthrogryposis and dysmorphic features[J]. J Appl Genet, 2017, 58(2):199-203.
[9]
Jungbluth H, Voermans NC. Congenital myopathies:not only a paediatric topic[J]. Curr Opin Neurol, 2016, 29(5):642-650.
[10]
Park YE, Shin JH, Kang B, et al. NEB-related core-rod myopathy with distinct clinical and pathological features[J]. Muscle Nerve, 2016, 53(3):479-484.
[11]
Laing NG, Dye DE, Wallgren-Pettersson C, et al. Mutations and polymorphisms of the skeletal muscle alpha-actin gene (ACTA1)[J]. Hum Mutat, 2009, 30(9):1267-1277.
[12]
Lehtokari VL, Pelin K, Donner K, et al. Identification of a founder mutation in TPM3 in nemaline myopathy patients of Turkish origin[J]. Eur J Hum Genet, 2008, 16(9):1055-1061.
[13]
Monnier N, Lunardi J, Marty I, et al. Absence of betatropomyosin is a new cause of Escobar syndrome associated with nemaline myopathy[J]. Neuromuscul Disord, 2009, 19(2):118-123.
[14]
Amarasinghe C, Hossain MM, Jin JP. Functional basis of three new recessive mutations of slow skeletal muscle troponin T found in non-Amish TNNT1 nemaline myopathies[J]. Biochemistry, 2016, 55(32):4560-4567.
[15]
Ockeloen CW, Gilhuis HJ, Pfundt R, et al. Congenital myopathy caused by a novel missense mutation in the CFL2 gene[J]. Neuromuscul Disord, 2012, 22(7):632-639.
[16]
Seferian AM, Malfatti E, Bosson C, et al. Mild clinical presentation in KLHL40-related nemaline myopathy (NEM 8)[J]. Neuromuscul Disord, 2016, 26(10):712-716.
[17]
Gupta VA, Ravenscroft G, Shaheen R, et al. Identification of KLHL41 mutations implicates BTB-Kelch-mediated ubiquitination as an alternate pathway to myofibrillar disruption in nemaline myopathy[J]. Am J Hum Genet, 2013, 93(6):1108-1117.
[18]
Yuen M, Sandaradura SA, Dowling JJ, et al. Leiomodin-3 dysfunction results in thin filament disorganization and nemaline myopathy[J]. J Clin Invest, 2015, 125(1):456-457.
[19]
Lornage X, Malfatti E, Cheraud C, et al. Recessive MYPN mutations cause cap myopathy with occasional nemaline rods[J]. Ann Neurol, 2017, 81(3):467-473.
[20]
Malfatti E, Bohm J, Lacene E, et al. A premature stop codon in MYO18B is associated with severe nemaline myopathy with cardiomyopathy[J]. J Neuromuscul Dis, 2015, 2(3):219-227.
[21]
Jungbluth H, Treves S, Zorzato F, et al. Congenital myopathies:disorders of excitation-contraction coupling and muscle contraction[J]. Nat Rev Neurol, 2018, 14(3):151-167.
[22]
Agrawal PB, Strickland CD, Midgett C, et al. Heterogeneity of nemaline myopathy cases with skeletal muscle alpha-actin gene mutations[J]. Ann Neurol, 2004, 56(1):86-96.
[23]
Findlay AR, Goyal NA, Mozaffar T. An overview of polymyositis and dermatomyositis[J]. Muscle Nerve, 2015, 51(5):638-656.
[24]
Turner C, Hilton-Jones D. Myotonic dystrophy:diagnosis, management and new therapies[J]. Curr Opin Neurol, 2014, 27(5):599-606.
[25]
Shah DU, Darras BT, Markowitz JA, et al. The spectrum of myotonic and myopathic disorders in a pediatric electromyography laboratory over 12 years[J]. Pediatr Neurol, 2012, 47(2):97-100.
[26]
Scarpelli M, Todeschini A, Volonghi I, et al. Mitochondrial diseases:advances and issues[J]. Appl Clin Genet, 2017, 10:21-26.
[27]
Voermans NC, Benveniste O, Minnema MC, et al. Sporadic late-onset nemaline myopathy with MGUS:long-term followup after melphalan and SCT[J]. Neurology, 2014, 83(23):2133-2139.
