Group of muscular dystrophies with a common histological picture and the mutations of which concern proteins associated with the Z zone of muscle fibers.

Muscle biopsy shows a dystrophy with a degeneration of muscle fibers combined with a fibrosis of necrosis; the typical image is that of a myofibril disorganization that starts at the level of the Z zone and is accompanied by an accumulation of products of degradation of microfibrils and proteins the expression of which is ectopic at this level. One can also observe, there where the microfibrils have disappeared, an aggregation of degraded filamentous material, of autophagic vacuoles and piles of glycogen.

The clinical forms are variable: the disease occurs generally between 35 and 50 years of age, with, most often, a progressive distal muscle weakness but a cardiac involvement (cardiomyopathy, conduction disorders, arrhythmia). CPK level  is high.

According to the protein which is associated with the mutated Z zone, there are:

 

1)        myofibrillar myopathy type 1 (desminopathy) [MIM 601 419]: autosomal dominant transmission of a mutation of the DES gene (2q35) coding for desmin, a protein that forms an intermediate filament type III ensuring the integrity of the muscle structure and its resistance to external mechanical stresses. The majority of patients show the first signs between 10 and 60 years of age. Distal or girdle or scapuloperonial muscular weakness; muscle atrophy with dysphagia, dysarthria. Arrhythmogenic cardiomyopathy of the right ventricle (type 7) is usual. Other presentations resemble Emery-Dreifuss disease and other mutations of the same gene produce autosomal dominant or recessive girdle dystrophy.

2)        myofibrillar myopathy type 2 (αβ-crystallinopathy) [MIM 608 810]: autosomal dominant transmission of a mutation of the CRYAB gene (11q23.1);  α-crystallins are small proteins that group together in clusters that bind to abnormal or denatured proteins to prevent their aggregation in the cell. αβ-crystallin is present in the lens and the skeletal and cardiac muscles. The disease usually begins in adulthood with distal and proximal muscle weakness, symmetrical and associated with amyotrophy. Sometimes: cataract, weakness of the palatopharyngeal muscles, cardiomyopathy, respiratory failure. A particular mutation [MIM 613 869] leads to hypertonic muscular dystrophy in native Canadians (Cree Indians): presence of a rapidly progressive muscle rigidity in the limbs and trunk from the first weeks of life; this rigidity is resistant to myorelaxants; severe respiratory failure and death in the first 3 years of life.

3)        myofibrillar myopathy type 3 (myotilinopathies) [MIM 609 200]: autosomal dominant transmission of a mutation of the MYOT gene (5q31); long classified as a girdle dystrophy type LGMD1A. Onset in adulthood (60 years of age); sometimes cardiac involvement or associated peripheral neuropathy.

4)        myofibrillar myopathy type 4 [MIM 609 452]: autosomal dominant transmission of a mutation of the LDB3 gene (10q23.2)

5)        myofibrillar myopathy type 5 (filaminopathy) [MIM 609 524]: autosomal dominant transmission of a mutation of the FLNC gene (7q32.1); filamins are large proteins of the cytoskeleton. Onset in adulthood with progressive muscle weakness; cardiomyopathy, respiratory failure and peripheral neuropathy then appear. A related form that manifests itself in early childhood has recently been described following autosomal recessive transmission of a mutation of the FILIP1 (Filamin A interacting protein 1) gene (6q14.1): it presents as a combination of developmental delay, cerebral malformation, dysmorphism and myopathy.

6)        myofibrillar myopathy type 6 (BAG-3pathy): autosomal dominant transmission of a mutation of the BAG3 gene (10q26.11)  coding for a co-chaperone protein that participates in the degradation of malformed or aggregated proteins. Onset in childhood with severe and progressive muscle weakness: cardiomyopathy and respiratory failure by paralysis of the diaphragm then appear; sometimes there is an clinical picture of extreme 'rigid spine'.

7)        myofibrillar myopathy type 7 [MIM 617 114]: autosomal recessive transmission of a mutation of the KY gene (3q22.2)

8)        myofibrillar myopathy type 8 [MIM 617 258]: autosomal recessive transmission of a mutation in the PYROXD1 gene (12p12.1)

9)        myofibrillar myopathy type 9 with early respiratory failure (titinopathy, HMERF) [MIM 603 689]: mutation of the TTN gene (2q31.2) coding for titin; see titinopathies.

Anesthetic implications: 

echocardiography and ECG preoperative; assessment of respiratory function; avoid succinylcholine and tourniquets (?). No known association with malignant hyperthermia. No increased risk of PRIS with TIVA propofol infusion. Altough no cases of rhabdomyolysis induced by the halogenated agents has been reported, it is wise to avoid them..

References : 

-         Selcen D. 
Myofibrillar myopathies. 
Neuromusc Disord 2011 ; 21 : 161-71.

-        Cawkwell GD.
Pathological case of the month:progressive hypertonic muscular dystrophy.
Arch Pediatr Adolesc Med 2001; 155: 853-4.

-        Forrest KML, Al-Sarraj S, Sewry C et al.
Infantile-onset myofibrillar myopathy due to recessive CRYAB mutations.
Neuromusc Disord 2011; 21: 37-40.

-         Latham GJ, Lopez G. 
Anesthetic considerations in myofibrillar myopathy. 
Pediatr Anesth 2015; 25:231-238 

-        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: February 2024