Nelson 648.2: Congenital Muscle Fiber-Type Disproportion (CMFTD)

Gene	Inheritance	Protein	Clinical Notes	Associated Disorders
TPM3	AD / AR	Tropomyosin-3	Most common genetic cause of isolated CMFTD	Nemaline myopathy, cap disease
TPM2	AD	Tropomyosin-2 (beta)	CMFTD phenotype	Nemaline myopathy, cap disease
ACTA1	AD / AR	Skeletal muscle α-actin	Minority of CMFTD; severe nemaline also	Nemaline myopathy, zebra body myopathy
RYR1	AR / AD	Ryanodine receptor	CMFTD without cores on biopsy	Central core, multiminicore, MH
MYH7	AD	Myosin heavy chain 7	CMFTD with cardiomyopathy	Myosin storage myopathy
LMNA	AD / AR	Lamin A/C	Familial CMFTD with cardiac risk	Emery-Dreifuss, LGMD1B

🔬 Diagnostic Criteria (Muscle Biopsy)

Congenital muscle fiber-type disproportion (CMFTD) is a syndrome, not a single disease. Requires:

Type I fibers are uniformly small (mean diameter at least 12% smaller than type II fibers)
Type I fibers are more numerous than type II fibers (predominance)
Type II fibers are normal or hypertrophic
Absence of other primary myopathic features (necrosis, regeneration, fibrosis, rods, cores, central nuclei)

Associations: Also seen in myotonic dystrophy, nemaline myopathy, Krabbe disease, cerebellar hypoplasia, fetal alcohol syndrome.

Data from Nelson 648.2; Manzur AY. Congenital muscle fiber-type disproportion.

🧬 648.2 · Congenital Muscle Fiber-Type Disproportion (CMFTD)