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Congenital myopathies | Histological features | Clinical features | Genes Mutated | Inheritance |
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MYOPATHIES WITH “RODS” (NEMALINE MYOPATHIES) | Presence of nemaline bodies or rods (protein aggregates) | Diaphragm weakness, distal weakness in lower extremities, congenital arthrogryposis, severe facial and bulbar weakness, severe hypotonia, and hyporeactivity, progressive respiratory failure | TPM3 (1q21.3) NEB (2q22.3) ACTA 1 (1q42.13) TPM2 (9p13.3) TNNT1 (19q13.42) KBTBD 13 (15q22.31) CFL2 (14q13.1) | AD or AR AR AD or sporadic, AR AD AR(Amish private mutation) AD AR |
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MYOPATHIES WITH CENTRALIZED NUCLEI | | | | |
Myotubular myopathies (XLMTM) | Muscle fibers similar to myotubes (normally observed at 8-15 weeks’ gestation) | Severe prenatal or neonatal myopathy, reduced fetal movements, polyhydramnios, swallowing difficulties, severe generalized hypotonia and weakness from birth, progressive ophthalmoparesis, severe respiratory insufficiency requiring ventilator support | MTM1 (Xq28) | Recessive X-linked |
Centronuclear myopathies | High incidence of centrally and/or internally placed nuclei in rows in muscle fibers | Progressive ophthalmoparesis, early respiratory failure, progressive craniofacial deformities | DNM2 (19q13.1) MYF6 (12q21.31) CCDC78 (16p13.3) BIN1 (2q14.3) | AD AD AD AR |
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MYOPATHIES WITH FIBER TYPE DISPROPORTION | Type 1 fibers are consistently and significantly smaller (hypotrophic) than type 2 fibers. Disproporzione del calibro delle fibre: fibre del tipo 1 (fibre lente) sono più piccole (almeno del 40%) rispetto alle fibre del tipo 2 (fibre veloci) | Low tone without other distinguishing characteristics | ACTA1 (1q42.1) Locus 2 (Xq13.1-q22.1) SEPN1 (1p36.11) TPM3 (1q21.2) TPM2 (9p13) MYL2 (12q24.11) | AD AR AR AD AD AR |
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MYOPATHIES WITH “CORES” | Cores: well-delimited, rounded areas devoid of oxidative staining, located in the cytoplasm of the muscle fibers. | | | |
Central core myopathy | Single and central cores in muscle fibers | Decreased fetal movement during pregnancy, muscle pain/cramps, global hypotonia, weakness of the facial muscles, severe skeletal malformations, possible malignant hyperthermia | RYR1 (19q13.1) SEPN1 (1p36.11) TTN (2q31.2) MYH7 (14q12) | AR AR or sporadic AR AD |
Multiminicore myopathy | Multiple, short areas of sarcomere disorganization containing reduced numbers of mitochondria in skeletal muscle fibers | Neonatal hypotonia, global muscle weakness, delayed motor development | RYR1 (19q13.1) SEPN1 (1p36.11) TTN (2q31.2) MYH7 (14q12) | AR AR or sporadic AR AD |
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