Diagnóstico diferencial das distrofias musculares
                        cintura-membros recessivas comuns: como e por quê?

Cotta, Ana; Carvalho, Elmano; da-Cunha-Júnior, Antonio Lopes; Paim, Júlia Filardi; Navarro, Monica M.; Valicek, Jaquelin; Menezes, Miriam Melo; Nunes, Simone Vilela; Xavier Neto, Rafael; Takata, Reinaldo Issao; Vargas, Antonio Pedro

doi:10.1590/0004-282X20140110

Ana Cotta

Rede SARAH de Hospitais de Reabilitação, Departamento de Patologia, Belo Horizonte MG, Brazil

Elmano Carvalho

Rede SARAH de Hospitais de Reabilitação, Departamento de Neurofisiologia, Belo Horizonte MG, Brazil

Antonio Lopes da-Cunha-Júnior

Rede SARAH de Hospitais de Reabilitação, Departamento de Radiologia, Belo Horizonte MG, Brazil

Júlia Filardi Paim

Rede SARAH de Hospitais de Reabilitação, Departamento de Patologia, Belo Horizonte MG, Brazil

Monica M. Navarro

Rede SARAH de Hospitais de Reabilitação, Departamento de Pediatria, Belo Horizonte MG, Brazil

Jaquelin Valicek

Rede SARAH de Hospitais de Reabilitação, Departamento de Neurofisiologia, Belo Horizonte MG, Brazil

Miriam Melo Menezes

Rede SARAH de Hospitais de Reabilitação, Departamento de Neurologia, Belo Horizonte MG, Brazil

Simone Vilela Nunes

Rede SARAH de Hospitais de Reabilitação, Departamento de Neurologia, Belo Horizonte MG, Brazil

Rafael Xavier Neto

Rede SARAH de Hospitais de Reabilitação, Departamento de Neurologia, Belo Horizonte MG, Brazil

Reinaldo Issao Takata

Rede SARAH de Hospitais de Reabilitação, Departamento de Biologia Molecular, Brasília DF, Brazil

Antonio Pedro Vargas

Rede SARAH de Hospitais de Reabilitação, Departamento de Neurologia, Belo Horizonte MG, Brazil

Correspondence: Ana Cotta; Rede SARAH de Hospitais de Reabilitação; Av. Amazonas, 5953 Gameleira; 30510-000 Belo Horizonte MG, Brasil; E-mail: ana_cotta@yahoo.com.br

Conflict of interest: There is no conflict of interest to declare.

Disease	Gene	Locus	Gene product
LGMD1A	MYOT	5q31	myotilin
LGMD1B	LMNA	1q22	lamin A/C
LGMD1C	CAV3	3p25	caveolin-3
LGMD1D*	DNAJB6	7q36.2	HSP-40 homologue subfamily B, number 6
LGMD1E*	DES	2q35	desmin
LGMD1F	TNPO3	7q32	transportin 3
LGMD1G	HNRPDL	4q21	heterogeneous nuclear ribonucleoprotein D-like
LGMD1H	-	3p25.1-p23	-
LGMD2A	CAPN3	15q15.1	calpain-3
LGMD2B	DYSF	2p13	dysferlin
LGMD2C	SGCG	13q12	gamma-sarcoglycan
LGMD2D	SGCA	17q12-q21.33	alpha-sarcoglycan
LGMD2E	SGCB	4q12	beta-sarcoglycan
LGMD2F	SGCD	5q33	delta-sarcoglycan
LGMD2G	TCAP	17q12	telethonin (titin-cap)
LGMD2H	TRIM32	9q31.2	tripartite motif-containing 32
LGMD2I	FKRP	19q13.3	fukutin related protein
LGMD2J	TTN	2q31	titin
LGMD2K	POMT1	9q34	protein O-mannosyltransferase 1
LGMD2L	ANO5	11p14.3	anoctamin 5
LGMD2M	FKTN	9q31-q33	fukutin
LGMD2N	POMT2	14q24	protein O-mannosyltransferase 2
LGMD2O	POMGNT1	1p34	protein O-linked mannose beta 1,2-N-acetylglucosaminyl-transferase 1
LGMD2Q	PLEC1	8q24	plectin 1f
LGMD2R	DES	2q35	desmin
LGMD2S	TRAPPC11	4q35.1	trafficking protein particle complex 11
LGMD2T	GMPPB	3p21.31	GDP-mannose pyrophosphorylase B

Clinical and laboratorial findings	LGMD
Clinical and laboratorial findings	2A	2C-F*	2B	2I	2G
Mean onset age (years)²⁸28 . Sáenz A, Leturcq F, Cobo AM, et al. LGMD2A: genotype-phenotype correlations based on a large mutational survey on the calpain 3 gene. Brain 2005;128:732-742.^,³²32 . Klinge L, Dekomien G, Aboumousa A, et al. Sarcoglycanopathies: can muscle immunoanalysis predict the genotype? Neuromuscul Disord 2008;18:934-941.^,³⁵35 . Rosales XQ, Gastier-Foster JM, Lewis S, et al. Novel diagnostic features of dysferlinopathies. Muscle Nerve 2010;42:14-21.^,³⁶36 . Paradas C, González-Quereda L, De Luna N, et al. A new phenotype of dysferlinopathy with congenital onset. Neuromuscul Disord 2009;19:21-25.^,⁴⁵45 . Poppe M, Cree L, Bourke J, et al. The phenotype of limb-girdle muscular dystrophy type 2I. Neurology 2003;60:1246-1251.^,⁴⁹49 . Moreira ES, Wiltshire TJ, Faulkner G, et al. Limb-girdle muscular dystrophy type 2G is caused by mutations in the gene encoding the sarcomeric protein telethonin. Nat Genet 2000;24:163-166.	13	6	19	19	12
Typical onset age range (years)²⁸28 . Sáenz A, Leturcq F, Cobo AM, et al. LGMD2A: genotype-phenotype correlations based on a large mutational survey on the calpain 3 gene. Brain 2005;128:732-742.^,⁶6 . Engel AG, Franzini-Armstrong C. Myology 3rd ed. New York: McGraw-Hill, 2004:1-1960.^,³⁵35 . Rosales XQ, Gastier-Foster JM, Lewis S, et al. Novel diagnostic features of dysferlinopathies. Muscle Nerve 2010;42:14-21.^,⁴⁵45 . Poppe M, Cree L, Bourke J, et al. The phenotype of limb-girdle muscular dystrophy type 2I. Neurology 2003;60:1246-1251.^,¹¹11 . Vainzof M, Bushby K. Chapter 11. Muscular dystrophies presenting with proximal muscle weakness. In: Karpati G, Hilton-Jones D, Bushby K, Griggs RC.(EDS) Disorders of Voluntary Muscle 8th edition. Cambridge: Cambridge University Press, 2010:230-256.	8-15	6-8	17-25	2-40	9-15
Wide onset age range (years)²⁸28 . Sáenz A, Leturcq F, Cobo AM, et al. LGMD2A: genotype-phenotype correlations based on a large mutational survey on the calpain 3 gene. Brain 2005;128:732-742.^,³²32 . Klinge L, Dekomien G, Aboumousa A, et al. Sarcoglycanopathies: can muscle immunoanalysis predict the genotype? Neuromuscul Disord 2008;18:934-941.^,³⁶36 . Paradas C, González-Quereda L, De Luna N, et al. A new phenotype of dysferlinopathy with congenital onset. Neuromuscul Disord 2009;19:21-25.^,³⁷37 . Takahashi T, Aoki M, Suzuki N, et al. Clinical features and a mutation with late onset of limb girdle muscular dystrophy 2B. J Neurol Neurosurg Psychiatry 2013;84:433-440.^,⁴⁶46 . Boito CA, Melancini P, Vianello A, et al. Clinical and molecular characterization of patients with limb-girdle muscular dystrophy type 2I. Arch Neurol 2005;62:1894-1899.^,⁵¹51 . Paim JF, Cotta A, Vargas AP, et al. Muscle phenotypic variability in limb girdle muscular dystrophy 2G. J Mol Neurosci 2013;50:339-344.	1-67	1-30	1-58	2-50	1-20
Disease progression rate³3 . Nigro V, Aurino S, Piluso G. Limb girdle muscular dystrophies: update on genetic diagnosis and therapeutic approaches. Curr Opin Neurol 2011;24:429-436.	++	+++	+	++	+
Subacute start mimicking polymyositis³3 . Nigro V, Aurino S, Piluso G. Limb girdle muscular dystrophies: update on genetic diagnosis and therapeutic approaches. Curr Opin Neurol 2011;24:429-436.^,³⁸38 . Nguyen K, Bassez G, Krahn M, et al. Phenotypic study in 40 patients with dysferlin gene mutations: high frequency of atypical phenotypes. Arch Neurol 2007;64:1176-1182.^,⁴⁵45 . Poppe M, Cree L, Bourke J, et al. The phenotype of limb-girdle muscular dystrophy type 2I. Neurology 2003;60:1246-1251.^,⁴⁶46 . Boito CA, Melancini P, Vianello A, et al. Clinical and molecular characterization of patients with limb-girdle muscular dystrophy type 2I. Arch Neurol 2005;62:1894-1899.^,⁴⁹49 . Moreira ES, Wiltshire TJ, Faulkner G, et al. Limb-girdle muscular dystrophy type 2G is caused by mutations in the gene encoding the sarcomeric protein telethonin. Nat Genet 2000;24:163-166.	-/+	-	++	-	-
Ambulation loss (age in years)²⁸28 . Sáenz A, Leturcq F, Cobo AM, et al. LGMD2A: genotype-phenotype correlations based on a large mutational survey on the calpain 3 gene. Brain 2005;128:732-742.^,¹¹11 . Vainzof M, Bushby K. Chapter 11. Muscular dystrophies presenting with proximal muscle weakness. In: Karpati G, Hilton-Jones D, Bushby K, Griggs RC.(EDS) Disorders of Voluntary Muscle 8th edition. Cambridge: Cambridge University Press, 2010:230-256.^,⁶6 . Engel AG, Franzini-Armstrong C. Myology 3rd ed. New York: McGraw-Hill, 2004:1-1960.^,³⁸38 . Nguyen K, Bassez G, Krahn M, et al. Phenotypic study in 40 patients with dysferlin gene mutations: high frequency of atypical phenotypes. Arch Neurol 2007;64:1176-1182.^,⁴⁵45 . Poppe M, Cree L, Bourke J, et al. The phenotype of limb-girdle muscular dystrophy type 2I. Neurology 2003;60:1246-1251.^,⁴⁹49 . Moreira ES, Wiltshire TJ, Faulkner G, et al. Limb-girdle muscular dystrophy type 2G is caused by mutations in the gene encoding the sarcomeric protein telethonin. Nat Genet 2000;24:163-166.	21-40	12-16	18-58	>12	>30
Cardiomyopathy³3 . Nigro V, Aurino S, Piluso G. Limb girdle muscular dystrophies: update on genetic diagnosis and therapeutic approaches. Curr Opin Neurol 2011;24:429-436.^,²⁸28 . Sáenz A, Leturcq F, Cobo AM, et al. LGMD2A: genotype-phenotype correlations based on a large mutational survey on the calpain 3 gene. Brain 2005;128:732-742.^,²⁵25 . Fanin M, Melacini P, Boito C, Pegoraro E, Angelini C. LGMD2E patients risk developing dilated cardiomyopathy. Neuromuscul Disord 2003;13:303-309.^,¹1 . Norwood FL, de Visser M, Eymard B, Lochmüller H, Bushby K and Members of EFNS Guideline Task Force. EFNS guideline on diagnosis and management of limb girdle muscular dystrophies. Eur J Neurol 2007;14:1305-1312.^,³⁸38 . Nguyen K, Bassez G, Krahn M, et al. Phenotypic study in 40 patients with dysferlin gene mutations: high frequency of atypical phenotypes. Arch Neurol 2007;64:1176-1182.^,⁴⁵45 . Poppe M, Cree L, Bourke J, et al. The phenotype of limb-girdle muscular dystrophy type 2I. Neurology 2003;60:1246-1251.^,⁴⁶46 . Boito CA, Melancini P, Vianello A, et al. Clinical and molecular characterization of patients with limb-girdle muscular dystrophy type 2I. Arch Neurol 2005;62:1894-1899.^,¹¹11 . Vainzof M, Bushby K. Chapter 11. Muscular dystrophies presenting with proximal muscle weakness. In: Karpati G, Hilton-Jones D, Bushby K, Griggs RC.(EDS) Disorders of Voluntary Muscle 8th edition. Cambridge: Cambridge University Press, 2010:230-256.	-	+++	-	+	+
Early respiratory abnormality²⁸28 . Sáenz A, Leturcq F, Cobo AM, et al. LGMD2A: genotype-phenotype correlations based on a large mutational survey on the calpain 3 gene. Brain 2005;128:732-742.^,³²32 . Klinge L, Dekomien G, Aboumousa A, et al. Sarcoglycanopathies: can muscle immunoanalysis predict the genotype? Neuromuscul Disord 2008;18:934-941.^,¹1 . Norwood FL, de Visser M, Eymard B, Lochmüller H, Bushby K and Members of EFNS Guideline Task Force. EFNS guideline on diagnosis and management of limb girdle muscular dystrophies. Eur J Neurol 2007;14:1305-1312.^,³⁸38 . Nguyen K, Bassez G, Krahn M, et al. Phenotypic study in 40 patients with dysferlin gene mutations: high frequency of atypical phenotypes. Arch Neurol 2007;64:1176-1182.^,⁴⁵45 . Poppe M, Cree L, Bourke J, et al. The phenotype of limb-girdle muscular dystrophy type 2I. Neurology 2003;60:1246-1251.^,⁴⁶46 . Boito CA, Melancini P, Vianello A, et al. Clinical and molecular characterization of patients with limb-girdle muscular dystrophy type 2I. Arch Neurol 2005;62:1894-1899.^,¹¹11 . Vainzof M, Bushby K. Chapter 11. Muscular dystrophies presenting with proximal muscle weakness. In: Karpati G, Hilton-Jones D, Bushby K, Griggs RC.(EDS) Disorders of Voluntary Muscle 8th edition. Cambridge: Cambridge University Press, 2010:230-256.	-	-	-	+	-
Upper and lower limbs interval (years)²⁸28 . Sáenz A, Leturcq F, Cobo AM, et al. LGMD2A: genotype-phenotype correlations based on a large mutational survey on the calpain 3 gene. Brain 2005;128:732-742.^,⁶6 . Engel AG, Franzini-Armstrong C. Myology 3rd ed. New York: McGraw-Hill, 2004:1-1960.^,³⁸38 . Nguyen K, Bassez G, Krahn M, et al. Phenotypic study in 40 patients with dysferlin gene mutations: high frequency of atypical phenotypes. Arch Neurol 2007;64:1176-1182.^,⁴⁵45 . Poppe M, Cree L, Bourke J, et al. The phenotype of limb-girdle muscular dystrophy type 2I. Neurology 2003;60:1246-1251.^,¹¹11 . Vainzof M, Bushby K. Chapter 11. Muscular dystrophies presenting with proximal muscle weakness. In: Karpati G, Hilton-Jones D, Bushby K, Griggs RC.(EDS) Disorders of Voluntary Muscle 8th edition. Cambridge: Cambridge University Press, 2010:230-256.	<2**	**	>6**	**	**
Increased calf¹1 . Norwood FL, de Visser M, Eymard B, Lochmüller H, Bushby K and Members of EFNS Guideline Task Force. EFNS guideline on diagnosis and management of limb girdle muscular dystrophies. Eur J Neurol 2007;14:1305-1312.^,³3 . Nigro V, Aurino S, Piluso G. Limb girdle muscular dystrophies: update on genetic diagnosis and therapeutic approaches. Curr Opin Neurol 2011;24:429-436.^,²⁸28 . Sáenz A, Leturcq F, Cobo AM, et al. LGMD2A: genotype-phenotype correlations based on a large mutational survey on the calpain 3 gene. Brain 2005;128:732-742.^,¹¹11 . Vainzof M, Bushby K. Chapter 11. Muscular dystrophies presenting with proximal muscle weakness. In: Karpati G, Hilton-Jones D, Bushby K, Griggs RC.(EDS) Disorders of Voluntary Muscle 8th edition. Cambridge: Cambridge University Press, 2010:230-256.^,³²32 . Klinge L, Dekomien G, Aboumousa A, et al. Sarcoglycanopathies: can muscle immunoanalysis predict the genotype? Neuromuscul Disord 2008;18:934-941.^,³⁵35 . Rosales XQ, Gastier-Foster JM, Lewis S, et al. Novel diagnostic features of dysferlinopathies. Muscle Nerve 2010;42:14-21.^,⁴⁵45 . Poppe M, Cree L, Bourke J, et al. The phenotype of limb-girdle muscular dystrophy type 2I. Neurology 2003;60:1246-1251.^,⁴⁶46 . Boito CA, Melancini P, Vianello A, et al. Clinical and molecular characterization of patients with limb-girdle muscular dystrophy type 2I. Arch Neurol 2005;62:1894-1899.	-/+	++	-/+	++	++
Winged scapula³3 . Nigro V, Aurino S, Piluso G. Limb girdle muscular dystrophies: update on genetic diagnosis and therapeutic approaches. Curr Opin Neurol 2011;24:429-436.^,²⁸28 . Sáenz A, Leturcq F, Cobo AM, et al. LGMD2A: genotype-phenotype correlations based on a large mutational survey on the calpain 3 gene. Brain 2005;128:732-742.^,¹¹11 . Vainzof M, Bushby K. Chapter 11. Muscular dystrophies presenting with proximal muscle weakness. In: Karpati G, Hilton-Jones D, Bushby K, Griggs RC.(EDS) Disorders of Voluntary Muscle 8th edition. Cambridge: Cambridge University Press, 2010:230-256.^,³²32 . Klinge L, Dekomien G, Aboumousa A, et al. Sarcoglycanopathies: can muscle immunoanalysis predict the genotype? Neuromuscul Disord 2008;18:934-941.^,³⁸38 . Nguyen K, Bassez G, Krahn M, et al. Phenotypic study in 40 patients with dysferlin gene mutations: high frequency of atypical phenotypes. Arch Neurol 2007;64:1176-1182.^,⁴⁵45 . Poppe M, Cree L, Bourke J, et al. The phenotype of limb-girdle muscular dystrophy type 2I. Neurology 2003;60:1246-1251.^,⁴⁶46 . Boito CA, Melancini P, Vianello A, et al. Clinical and molecular characterization of patients with limb-girdle muscular dystrophy type 2I. Arch Neurol 2005;62:1894-1899.	++	++	-	-/+	+
“Dystrophinopathy-like” phenotype³3 . Nigro V, Aurino S, Piluso G. Limb girdle muscular dystrophies: update on genetic diagnosis and therapeutic approaches. Curr Opin Neurol 2011;24:429-436.^,¹¹11 . Vainzof M, Bushby K. Chapter 11. Muscular dystrophies presenting with proximal muscle weakness. In: Karpati G, Hilton-Jones D, Bushby K, Griggs RC.(EDS) Disorders of Voluntary Muscle 8th edition. Cambridge: Cambridge University Press, 2010:230-256.^,³²32 . Klinge L, Dekomien G, Aboumousa A, et al. Sarcoglycanopathies: can muscle immunoanalysis predict the genotype? Neuromuscul Disord 2008;18:934-941.^,³⁸38 . Nguyen K, Bassez G, Krahn M, et al. Phenotypic study in 40 patients with dysferlin gene mutations: high frequency of atypical phenotypes. Arch Neurol 2007;64:1176-1182.^,⁴⁵45 . Poppe M, Cree L, Bourke J, et al. The phenotype of limb-girdle muscular dystrophy type 2I. Neurology 2003;60:1246-1251.^,⁴⁶46 . Boito CA, Melancini P, Vianello A, et al. Clinical and molecular characterization of patients with limb-girdle muscular dystrophy type 2I. Arch Neurol 2005;62:1894-1899.	-/+	++	-	++	-
Serum creatine kinase (CPK) times increase¹1 . Norwood FL, de Visser M, Eymard B, Lochmüller H, Bushby K and Members of EFNS Guideline Task Force. EFNS guideline on diagnosis and management of limb girdle muscular dystrophies. Eur J Neurol 2007;14:1305-1312.^,⁵¹51 . Paim JF, Cotta A, Vargas AP, et al. Muscle phenotypic variability in limb girdle muscular dystrophy 2G. J Mol Neurosci 2013;50:339-344.^,⁶²62 . Nigro V, Savarese M. Genetic basis of limb-girdle muscular dystrophies: the 2014 update. Acta Myol 2014;33:1-12.	3-20x	5-40x	10-70x	10-20x	1-30x
Distal myopathy phenotype¹1 . Norwood FL, de Visser M, Eymard B, Lochmüller H, Bushby K and Members of EFNS Guideline Task Force. EFNS guideline on diagnosis and management of limb girdle muscular dystrophies. Eur J Neurol 2007;14:1305-1312.^,³⁵35 . Rosales XQ, Gastier-Foster JM, Lewis S, et al. Novel diagnostic features of dysferlinopathies. Muscle Nerve 2010;42:14-21.^,³⁸38 . Nguyen K, Bassez G, Krahn M, et al. Phenotypic study in 40 patients with dysferlin gene mutations: high frequency of atypical phenotypes. Arch Neurol 2007;64:1176-1182.^,¹¹11 . Vainzof M, Bushby K. Chapter 11. Muscular dystrophies presenting with proximal muscle weakness. In: Karpati G, Hilton-Jones D, Bushby K, Griggs RC.(EDS) Disorders of Voluntary Muscle 8th edition. Cambridge: Cambridge University Press, 2010:230-256.	-	-	-/+	-	-/+
Contractures¹1 . Norwood FL, de Visser M, Eymard B, Lochmüller H, Bushby K and Members of EFNS Guideline Task Force. EFNS guideline on diagnosis and management of limb girdle muscular dystrophies. Eur J Neurol 2007;14:1305-1312.^,⁴⁵45 . Poppe M, Cree L, Bourke J, et al. The phenotype of limb-girdle muscular dystrophy type 2I. Neurology 2003;60:1246-1251.^,¹¹11 . Vainzof M, Bushby K. Chapter 11. Muscular dystrophies presenting with proximal muscle weakness. In: Karpati G, Hilton-Jones D, Bushby K, Griggs RC.(EDS) Disorders of Voluntary Muscle 8th edition. Cambridge: Cambridge University Press, 2010:230-256.	+	+	-	-	-

[1] Correspondence: Ana Cotta; Rede SARAH de Hospitais de Reabilitação; Av. Amazonas, 5953 Gameleira; 30510-000 Belo Horizonte MG, Brasil; E-mail: ana_cotta@yahoo.com.br

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Diagnóstico diferencial das distrofias musculares cintura-membros recessivas comuns: como e por quê?