Group of myopathies (Limb Girdle Muscular Dystrophies or LGMD) characterized involving mainly the scapular and pelvic girdles. There are two major clinical categories classified according to their mode of transmission and the deficient muscle protein, which may be a protein of the sarcolemma or the contractile apparatus (calpaine3, telethonine, titin, desmin). Cardiac involvement is possible but not always correlated with the importance of muscular pathology.

Forms with dominant transmission or LGMDD (10 % of cases )

Normal and low level of CPK

a)        LGMDD1 (formerly: LGMD1E) [MIM 603 511]: mutation of the DNAJB6 gene (7q36.3)

b)        LGMDD2 (formerly: LGMD1F) [MIM 608 423]: mutation of the TNPO3 gene (7q32) coding for transportin

c)        LGMDD3 (formerly: LGMD1G) [MIM 609 115]: mutation of the HNRNPDL gene (4q21.22)

d)        LGMDD4 [MIM 603 511]: mutation of the CAPN3 gene (15q15.1) coding for calpain

e)        LGMDD5 [MIM 158 810]: mutation of the COL6A1 gene (21q22.3) coding the α1 subunit of collagen 6, or COL6A2 (21q22.3)  coding for the α2 subunit of the collagen 6 or COL6A3 (2q37.3) coding the α3 subunit of collagen 6. Other mutations of these genes  cause  the Bethlem and Ullrich myopathies (see these terms)

f)        Myofibrillar myopathy type 3 (formerly LGMD1A) [MIM 159 000]: myotilin deficiency (MYOT gene (5q31)); the onset is marked by dysarthria in adulthood; cardiac involvement is present in 50 %; another mutation of this gene causes distal myotilininopathy (see myofibrillar myopathies)

g)        Emery-Dreifuss myopathy type 2 (formerly LGMD1B) [MIM 159 001 and 181 350]: lamin A/C deficiency (LMNA gene (1q22)): onset  between 5 and 20 years of age and may only be revealed by cardiac problems (A-V block, atrial arrhythmias, sudden death): frequent indication of an internal defibrillator

(h)        Rippling muscle disease (formerly LGMD1C [MIM 607 780 and 606 072](see this term): caveolin 3 deficiency (CAV3 gene (3p25.3)); clinical onset at any age; the disease results in cramps on exercise, waved contractions of the muscles following percussion, amyotrophy of the girdles or weakness of the distal muscles; the CPK level is moderately elevated. Other mutations in this gene produce idiopathic hyperCKemia, familial hypertrophic cardiomyopathy type 1, Tateyama distal myopathy and congenital long QT syndrome type 9.

i)        Fibrillary myopathy type 1 (formerly LGMD1D linked to DES) [MIM 601 419]: mutation of the DES gene (2q35) coding for desmin; other mutations in this gene produce an autosomal recessive limb girdle muscular dystrophy, dilated cardiomyopathy type 11, and arrhythmogenic cardiomyopathy of the right ventricle (see these terms)

j)        LGMD1H [MIM 613 530]: very rare mutation of a gene not yet identified (3p25.1-p23).

Forms with autosomal recessive transmission or LGMDR (90 % of cases) 

High CPK level.

• LGMDR1 (formerly LGMD2A) (25 %)[MIM 253,600], or Erb muscular dystrophy or calpain 3 deficiency (CAPN3 gene (15q15.1))  playing a role in muscle regeneration; it is the most common form; it begins between 8 and 15 years of age and is characterized by the presence of contractures with sometimes a Emery-Dreifuss phenotype; its progression is slow; there is sometimes a cardiomyopathy; CPK level is high; the prevalence is higher in some Amish communities, in La Réunion island, Brazil and in the Basque country
• LGMDR2 (formerly LGMD2B (20 %) [MIM 253 601] or dysferlin deficiency:  mutation of the DYSF gene (2p13.2) ;it begins around 20 years of age, results in muscle pain; there may be cardiomyopathy (rarely); CPK level is very high; other mutations in this gene can lead to Miyoshi's myopathy [MIM 613 318, 254 130](see this term)
• LGMDR3 (formerly LGMD2D) [MIM 608 099] due to a deficiency of α-sarcoglycan or sarcoglycanopathy or adhalinopathy (SGCA gene (17q12-q21.33), more common in Brazil and Europe.
• LGMDR4 (formerly LGMD2E) [MIM 600 900]: due to a deficiency of β-sarcoglycan (SCGB gene (4q12)).
• LGMDR5 (formerlyly LGMD2C) [MIM 253 700]: due to γ-sarcoglycan deficiency (SGCG gene (13q12.12)); more common in North Africa
• LGMDR6 (formerly LGMD2F) [MIM 601 287]: due to δ-sarcoglycan deficiency (CMS gene (5q33.3-q34))

The clinical presentation of the LGMDR3 to 6 forms, also called sarcoglycanopathies, is variable, often close to Duchenne's disease with an onset between 6 and 8 years of age, hypertrophy of the calves and tongue, rapid progression with cardiac involvement (30 %) (ventricular dilatation, cardiomyopathy), but the evolution may be slower; cases of rhabdomyolysis (myoglobinuria = emission of red brown urine) after exercise or a febrile episode have been described; the disease is as common in girls as in boys; CPK level is high;

• LGMDR7 (formerly LGMD2G) [MIM 601 954]: telethonin deficiency (TCAP gene (17q12)), only described in Brazil; it begins between 2 and 15 years of age; it results in hypertrophy of the calves and cardiac involvement in 50 % of cases; the CPK level is high;
• LGMDR8 (formerly LGMD2H) [MIM 254 110]: TRIM32 protein deficiency(9q31.1); it begins between 8 and 25 years of age; its progression is slow; it is only described in Hutterites in Canada; CPK level is high; other mutations in this gene can cause sarcotubular myopathy
• LGDMR9 (formerly LGMD2I) [MIM 607 155]: deficiency of fukutin-related protein (FKRP gene (19q13.32)); observed mainly in Northern Europe, it begins between 10 and 20 years of age; it results in contractures, ventricular conduction disorders and dilated cardiomyopathy in 50 % of cases; in case of onset in early childhood, there is hypertrophy of the tongue; CPK level is high; other mutations in this gene can cause congenital dystrophy with laminin-α2 deficiency
• LGMDR10 (formerly LGMD2J) [MIM 608 807]: titin deficiency (TTN gene (2q31. 2)); only described in Finland, it begins between 10 and 30 years of age; its progression is slow, without cardiac involvement; CPK level is high; see also titinopathies
• LGMDR11 (formerly LGMD2K) [MIM 609,308]: POMT1 deficiency (9q34. 13); it begins in childhood; its progression is slow with contractures;  other mutations of this gene can cause severe Walker-Warburg congenital dystrophy
• LGDMR12 (formerly LGMD2L) [MIM 611 307]: anoctamin 5 deficiency (ANO5 gene (11p14.3)); it begins at a variable age; the involvement is sometimes asymmetric; the CPK level is high; other mutations of this gene can lead to Miyoshi's myopathy
• LGMDR13 (formerly LGMD2M) [MIM 611 588]: fukutin deficiency(9q31.2): it begins in early childhood (hypotonia worsening in case of viral pathology); its progression is slow with possible cardiorespiratory involvement: cerebral MRI is normal; CPK level is high; other mutations of this gene can cause severe Fukuyama-type congenital dystrophy;
• LGMDR14 (formerly LGMD2N) [MIM 613 158]: POMT2 deficiency (POMT2 gene (14q24.3)); clinical involvement of varying severity; CPK level is high.
• LGMDR15 (formerly LGMD2O) [MIM 613 157]: protein-O-linked mannose-acetylglucosamininyltransferase 1 deficiency (POMGNT1 gene (1 p34. 1)).
• LGMDR16 (formerly LGMD2P) [MIM 613 818]: deficiency in  a glycoprotein1 associated with dystrophin following a mutation of the DAG1 gene (3p21.31)
• LGMDR17 (formerly LGMD2Q) [MIM 613 723]: deficiency of plectin 1, a protein associated with the sarcolemma at the Z-discs, following a mutation of the PLEC1 gene (8q24). Other mutations of this gene can lead to epidermolysis bullosa associated with muscular dystrophy, a myasthenic syndrome or ophthalmoplegia
• LGMDR18 (formerly LGMD2S) [MIM 615 356]: TRAPPC11 gene mutation (4q35.1)
• LGMDR19 (formerly LGMD2T) [MIM 615 352]: mutation of the GMPPB gene (3p21.31) coding for GDP-mannose pyrophosphorylase B
• LGMDR20 (formerly LGMD2U) [MIM 616,052]: mutation of the ISPD gene (7p21.2-p21.1)
• LGMDR21 (formerly LGMD2Z) [MIM 617 232]: mutation of the POGLUT1 gene (3q13.33)
• LGMDR22 (formerly: Bethlem myopathy type 1) [MIM 254 090]: mutation of the COL6A1 gene (21q22.3) coding for the α1 subunit of collagen 6, or COL6A2 (21q22.3) coding for the α2 subunit of collagen 6 or COL6A3 (2q37.3) coding the α3 subunit of collagen 6. Other mutations of these genes produce LGMDD5, Bethlem and Ullrich myopathies (see these terms)
• LGMDR23 [MIM 618 138]: mutation of the LAMA2 gene (6q22.33) coding for α2-laminin of merosine; other mutations in this gene produce a congenital muscular dystrophy
• LGMDR24 [MIM 618 135]: mutation of the POMGNT2 gene (3p22.1)
• LGMDR25 (formerly LGMD2X [MIM 616 812]: mutation of the POPDC1 or BVES gene (6q21) causing mainly cardiac rhythm disorders and a very discreet muscle involvement
• LGMDR26 [MIM 605 824]: mutation of the POPDC3 gene (6q21): onset in  adulthood with proximal weakness in the lower limbs; hypertrophy of the calves; CPK level is high
• Myofibrillar myopathy type 1 (formerly LGMD2R) [MIM 601 419 and 615 325]: mutation of the DES gene (2q35) coding for desmin
• Pompe disease (formerly LGMD2V) [MIM 232 300]: mutation of the GAA gene (17q25.3) coding for alpha glucosidase acid; see juvenile and late forms of Pompe disease (glycogenosis)
• Muscular dystrophy associated with PINCH2 (formerly LGMD2W) [MIM 616 827]: mutation of the LIMS2 or PINCH2 gene (2q14.3)
• Muscular dystrophy associated with TOR1AIP1 (formerlyly LGMD2Y) [MIM 617 072]: mutation of the TOR1AIP1 gene (1q25.2)  coding for a protein linked to laminin
• Muscular dystrophy with glycosylation disorder type Io [MIM 612 937]: mutation of the DPM3 gene (1q22).
• Scapuloperoneal muscular dystrophy with drooping head: mutation of the VCP gene (9p13.3)
• Girdle dystrophy with ophthalmoplegia: mutation of the PLEC gene (8q24.3) coding for plectin
• PYROXD1-associated girdle dystrophy: mutation of the PYROXD1 gene (12p12.1)
• KBTBD13-associated witgirdle dystrophy: mutation of the KBTBD13 gene (15q22.31)

Anesthetic implications: 

ECG and echocardiography preoperative; by analogy with the dystrophinopathies, it is prudent to avoid the halogenated agents especially if CPK level is high (risk of rhabdomyolysis).

References : 

-        Gurnaney H, Brown A, Litman RS. 
Malignant hyperthermia and muscular dystrophies. 
Anesth Analg 2009; 19:1043-8.

-         Moro C, Dangelser G, Veyckemans F. 
Prise en charge anesthésique d’un enfant atteint de delta-sarcoglycanopathie. 
Ann Fr Anesth Réanim 2007 ;26:359-62.

-        Hermans MCE, Pinto YM, Merkies ISJ, de Die-Smulders CEM, Crijns JHGM, Faber CG.
hereditary muscular dystrophies and the heart. 
Neuromuscul Disord 2010; 20: 479-92. (link to PDF)

-        Straub V, Bushby K. 
The childhood limb-girdle muscular dystrophies.
Sem Pediatr Neurol 2006; 13: 104-14.

-        Mercuri E, Muntoni F. 
Muscular dystrophies. 
Lancet 2013 ; 381 :845-60.

-        Chuang MC, Duggan LV, van Heest RD, MacLeod W. 
Laparoscopic cholecystectomy under spinal anesthesia in a patient with limb-girdle muscular dystrophy. 
Can J Anesth 2013 ; 60 : 1276-7.

-        Ceravolo F, Messina S, Roolico C, Strisciuglio P, Concolino D. 
Myoglobinuria as first clinical sign of a primary alpha-sarcoglycanopathy. 
Eur J Pediatr 2014; 173: 239-42.

-        Allen T, Maguire S.
Anaesthetic management of a woman with autosomal recessive limb-girdle muscular dystrophy for emergency caesarean section.
Int J Obstetr Anesth 2007; 16: 370-4.

-        Kabade SD, Bhosale R, Karthik S.
Case of limb-girdle muscular dystrophy for total thyroidectomy: anaesthetic management.
Indian J Anaesth 2016; 60:358-60.

-        Cao XQ, Joypaul K, Cao F, Gui LL, Hu JT, Mei W.
Anesthetic management of a patient with limb-girdle muscular dystrophy 2B : care-compliant case report and literature review.
BMC Anesthesiology 2019 ; 19 : 155

-        Benarroch L, Bonne G, Rivier F, Hamroun D.
The 2020 version of the gene table of neuromuscular disorders.
Neuromusc Dis 2019 ; 29 : 980-1018 ou  http://www.musclegenetable.fr.

Updated: June 2021