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

doi:10.1590/0004-282X20170151

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

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

Júlia Filardi Paim

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

Elmano Carvalho

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

Antonio Lopes da-Cunha-Júnior

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

Monica M. Navarro

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

Jaquelin Valicek

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

Miriam Melo Menezes

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

Simone Vilela Nunes

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

Rafael Xavier-Neto

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

Sidney Baptista Junior

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

Luciano Romero Lima

Rede SARAH de Hospitais de Reabilitação, Departamento de Informática, Belo Horizonte MG, Brasil

Reinaldo Issao Takata

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

Antonio Pedro Vargas

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

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

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

Inclusion criteria – 16 diagnostic categories
1) Steinert myotonic dystrophy
2) dystrophinopathy: Duchenne, Becker, intermediate phenotype, and female carriers
3) facioscapulohumeral muscular dystrophy
4) limb girdle muscular dystrophy
5) spinal muscular atrophy
6) congential muscular dystrophy (except collagen VI disorders)
7) Bethlem myopathy/ Ullrich congenital muscular dystrophy (type VI collagenopathy)
8) congenital myopathies (subtypes “central core” congenital myopathy, nemaline congenital myopathy, centronuclear/myotubular congenital myopathy, congenital fiber type disproportion, cap disease congenital myopathy)
9) congenital myasthenic syndrome
10) myofibrillar myopathy
11) glycogen-storage disease type V (McArdle disease)
12) glycogen-storage disease type II (Pompe disease)
13) dermatomyositis
14) sporadic inclusion body myositis
15) other inflammatory myopathies (polymyositis, nonspecific myositis, and immune mediated necrotizing myopathy)
16) mitochondrial myopathy
Exclusion criteria
1) myopathic abnormalities without other specification
2) neurogenic muscular abnormalities
3) rare genetic syndromes and other neuromuscular disorders not included in the 16 inclusion criteria diagnostic categories
4) duplicated diagnosis of patients submitted to both muscle biopsy and confirmatory molecular investigation

Neuromuscular disorders	Number of patients		Subtypes
Neuromuscular disorders	n	%	n	% within category
Steinert myotonic dystrophy	138	8.61
Mitochondriopathy	330	20.59
Dystrophinopathy - total of male patients	344	21.46
Duchenne type dystrophinopathy			287	83.43^a a: percentage from the total male dystrophinopathy patients;
Becker type dystrophinopathy			45	13.08^a a: percentage from the total male dystrophinopathy patients;
Intermediate phenotype dystrophinopathy			12	3.49^a a: percentage from the total male dystrophinopathy patients;
Asymptomatic female dystrophinopathy carriers	104	6.49
Symptomatic female dystrophinopathy carriers	12	0.75
Facioscapulohumeral muscular dystrophy	99	6.17
Limb girdle muscular dystrophy - total	157	9.79
Laminopathy (LGMD1B)			3	1.91^b b: percentage of limb girdle muscular dystrophy;
Caveolinopathy (LGMD1C)			3	1.91^b b: percentage of limb girdle muscular dystrophy;
Calpainopathy (LGMD2A)			24	15.29^b b: percentage of limb girdle muscular dystrophy;
Dysferlinopathy (LGMD2B)			29	18.47^b b: percentage of limb girdle muscular dystrophy;
Sarcoglycanopathy (LGMD2C, 2D, 2E, 2F)			26	16.56^b b: percentage of limb girdle muscular dystrophy;
Fukutin-related proteinopathy (LGMD2I)			8	5.10^b b: percentage of limb girdle muscular dystrophy;
Telethoninopathy (LGMD2G)			3	1.91^b b: percentage of limb girdle muscular dystrophy;
Undetermined			61	38.85^b b: percentage of limb girdle muscular dystrophy;
Spinal muscular atrophy	158	9.86
Congenital muscular dystrophy - total	79	4.93
Merosin negative			16	20.25^c c: percentage of congenital muscular dystrophy;
Type VI collagenopathy (Bethlem/ Ullrich)	13	0.81
Congenital myopathies – 5 subtypes	58	3.62
Central core/ multiminicore			26	44.83^d d: percentage of the five most common congenital myopathy subtypes;
Nemaline			16	2759^d d: percentage of the five most common congenital myopathy subtypes;
Centronuclear/myotubular			11	18.97^d d: percentage of the five most common congenital myopathy subtypes;
Cap disease			4	6.89^d d: percentage of the five most common congenital myopathy subtypes;
Congenital fiber type disproportion			1	1.72^d d: percentage of the five most common congenital myopathy subtypes;
Congenital myasthenic syndrome	7	0.44
Myofibrillar myopathy	11	0.68
Glycogenosis type V (McArdle disease)	5	0.31
Glycogenosis type II (Pompe disease)	4	0.25
Inflammatory myopathies - total	84	5.24
Dermatomyositis			34	40.47^e e: percentage of inflammatory myopathy.
Sporadic inclusion body myositis			15	17.86^e e: percentage of inflammatory myopathy.
Polymyositis/nonspecific myositis/ immune-mediated necrotizing myopathy			35	41.67^e e: percentage of inflammatory myopathy.
Total	1603	100

Subtype of limb girdle muscular dystrophy	Present study		Brazil		UK		Italy		Italy		Mexico		Australia
	Present study		Zatz et al., 2003⁵5. Zatz M, de Paula F, Starling A, Vainzof M. The 10 autosomal recessive limb-girdle muscular dystrophies. Neuromuscul Disord. 2003;13(7-8):532-44. https://doi.org/10.1016/S0960-8966(03)00100-7 https://doi.org/10.1016/S0960-8966(03)00...		Norwood et al., 2009¹⁴14. Norwood FL, Harling C, Chinnery PF, Eagle M, Bushby K, Straub V. Prevalence of genetic muscle disease in Northern England: in-depth analysis of a muscle clinic population. Brain. 2009;132(1 1):3175-86. https://doi.org/10.1093/brain/awp236 https://doi.org/10.1093/brain/awp236...		Fanin et al., 2009¹⁰10. Fanin M, Nascimbeni AC, Aurino S, Tasca E, Pegoraro E, Nigro V et al. Frequency of LGMD gene mutations in Italian patients with distinct clinical phenotypes. Neurology. 2009;72(16):1432-5. https://doi.org/10.1212/WNL.0b013e3181a1885e https://doi.org/10.1212/WNL.0b013e3181a1...		Guglieri et al., 2008¹¹11. Guglieri M, Magri F, D’Angelo MG, Prelle A, Morandi L, Rodolico C et al. Clinical, molecular, and protein correlations in a large sample of genetically diagnosed Italian limb girdle muscular dystrophy patients. Hum Mutat. 2008;29(2):258-66. https://doi.org/10.1002/humu.20642 https://doi.org/10.1002/humu.20642...		Gómez-Díaz etal, 2012¹²12. Gómez-Díaz B, Rosas-Vargas H, Roque-Ramírez B, Meza-Espinoza P Ruano-Calderón LA, Fernández-Valverde F et al. Immunodetection analysis of muscular dystrophies in Mexico. Muscle Nerve 2012;45(3):338-345. https://doi.org/10.1002/mus.22314 https://doi.org/10.1002/mus.22314...		Lo et al., 2008¹³13. Lo HP, Cooper ST, Evesson FJ, Seto JT, Chiotis M, Tay V et al. Limb-girdle muscular dystrophy: diagnostic evaluation, frequency and clues to pathogenesis. Neuromuscul Disord. 2008;18(1):34-44. https://doi.org/10.1016/j.nmd.2007.08.009 https://doi.org/10.1016/j.nmd.2007.08.00...
	n = 157 patients		n = 120 families		n = 43 patients		n = 346 patients		n = 155 families		n = 97 patients^b b: initial number of 290 biopsies (dystrophin and merosin deficiencies were excluded);		n = 76 patients
	n	%	n	%	n	%	n	%	n	%	n	%	n	%
LGMD1B laminopathy	3	2	NR	NR	6	14	5	2	NR	NR	NR	NR	1	1
LGMD1C caveolinopathy	3	2	NR	NR	NR	NR	5	2	2	1	3	3	2	3
LGMD2A calpainopathy	24	15	38^a a: absolute number of patients calculated based on the published percentages;	32	15	35	87	25	44	28	24	25	6	8
LGMD2B dysferlinopathy	29	18	27^a a: absolute number of patients calculated based on the published percentages;	22	2	5	39	11	29	19	39	40	4	5
LGMD2C-2D-2E-2F sarcoglycanopathy	26	17	38^a a: absolute number of patients calculated based on the published percentages;	32	8	18	52	15	28	18	30	31	2	2
LGMD2I fukutin-related proteinopathy	8	5	13^a a: absolute number of patients calculated based on the published percentages;	11	12	28	15	4	10	7	NR	NR	2	3
LGMD2G telethoninopathy	3	2	4^a a: absolute number of patients calculated based on the published percentages;	3	NR	NR	NR	NR	NR	NR	NR	NR	NR	NR
Indeterminate	61	39	NR	NR	NR	NR	141	40	42	27	NR	NR	59	78^c c: 78 indeterminate, of whom 58 have normal dysferlin expression and 20 have defective dysferlin. The frequencies of sarcoglycanopathy were calculated with the total of patients of each subtype: Fanin 200910, LGMD2C-2F = 1 1+30+10+1 = 52 (15%); Guglieri 200811, LGMD2C-2F = 32 = 4.5+8.4+4.5+0.7=18.1%. LGMD1B = laminopathy (limb girdle muscular dystrophy type 1B - LMNA gene mutation), LGMD1C = caveolinopathy (limb girdle muscular dystrophy type 1C - CAV3 gene mutation); LGMD2A = calpainopathy (limb girdle muscular dystrophy type 2A, CAPN3 gene mutation), LGMD2B = dysferlinopathy (limb girdle muscular dystrophy type 2B, DYSF gene mutation), LGMD2C-2D-2E-2F = sarcoglycanopathy (limb girdle muscular dystrophy types 2C-2D-2E-2F, LGMD2C gamma-sarcoglycan (SGCG) gene mutation, LGMD2D alpha-sarcoglycan (SGCA) gene mutation, LGMD2E beta-sarcoglycan (SGCB) gene mutation, and LGMD2F delta-sarcoglycan (SGCD) gene mutation; LGMD2I = fukutin-related proteinopathy (limb girdle muscular dystrophy type 2I, FKRP gene mutation) LGMD2G = telethoninopathy (limb girdle muscular dystrophy type 2G,TCAP gene mutation).
Other dystrophies	NR	NR	NR	NR	NR	NR	2	1	NR	NR	1	1	NR	NR

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

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Frequência relativa de diagnósticos neuromusculares comuns em um serviço de referência

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