Preferred Label : Congenital myopathy 2a, typical, autosomal dominant;
Symbol : CMYO2A;
CISMeF acronym : NEM3;
Type : Phenotype, molecular basis known;
Alternative titles and symbols : Myopathy, actin, congenital, with cores; Myopathy, actin, congenital, with excess of thin myofilaments; NEM3; Nemaline myopathy 3, with intranuclear rods; Nemaline myopathy 3;
Description : Nemaline myopathy is a form of congenital myopathy characterized by abnormal thread-
or rod-like structures in muscle fibers on histologic examination ('nema' is Greek
for 'thread'). The clinical phenotype is highly variable, with differing age at onset
and severity. Muscle weakness typically involves proximal muscles, with involvement
of the facial, bulbar, and respiratory muscles (Ilkovski et al., 2001). Attempts at
classification of nemaline myopathies into clinical subtypes have been complicated
by the overlap of clinical features and a continuous phenotypic spectrum of disease
(North et al., 1997; Wallgren-Pettersson et al., 1999; Ryan et al., 2001; Sanoudou
and Beggs, 2001). In general, 2 clinical groups can be readily distinguished: 'typical'
and 'severe.' Typical nemaline myopathy is the most common form, presenting as infantile
hypotonia and muscle weakness. It is slowly progressive or nonprogressive, and most
adults achieve ambulation. The severe form of the disorder is characterized by absence
of spontaneous movement or respiration at birth, arthrogryposis, and death in the
first months of life. Much less commonly, late-childhood or even adult-onset can occur.
However, adult-onset nemaline myopathy is usually not familial and may represent a
different disease (Wallgren-Pettersson et al., 1999; Sanoudou and Beggs, 2001). Myopathy
caused by mutations in the ACTA1 gene can show a range of clinical and pathologic
phenotypes. Some patients have classic rods, whereas others may also show intranuclear
rods, clumped filaments, cores, or fiber-type disproportion (see 255310), all of which
are nonspecific pathologic findings and not pathognomonic of a specific congenital
myopathy. The spectrum of clinical phenotypes caused by mutations in ACTA1 may result
from different mutations, modifying factors affecting the severity of the disorder,
variability in clinical care, or a combination of these factors (Nowak et al., 1999;
Kaindl et al., 2004). - Genetic Heterogeneity of Nemaline Myopathy See also NEM1 (609284),
caused by mutation in the tropomyosin-3 gene (TPM3; 191030) on chromosome 1q22; NEM2
(256030), caused by mutation in the nebulin gene (NEB; 161650) on chromosome 2q22;
NEM4 (609285), caused by mutation in the beta-tropomyosin gene (TPM2; 190990) on chromosome
9p13; NEM5 (605355), also known as Amish nemaline myopathy, caused by mutation in
the troponin T1 gene (TNNT1; 191041) on chromosome 19q13; NEM6 (609723), caused by
mutation in the KBTBD13 gene (613727) on chromosome 15q22.31, NEM7 (610687), caused
by mutation in the cofilin-2 gene (CFL2; 601443) on chromosome 14q12; and NEM8 (615348),
caused by mutation in the KLHL40 gene (615340), on chromosome 3p22. Six of the genes
encode components of skeletal muscle sarcomeric thin filaments (Sanoudou and Beggs,
2001). Mutations in the NEB gene are the most common cause of nemaline myopathy (Lehtokari
et al., 2006).;
Inheritance : Autosomal dominant; Autosomal recessive;
Molecular basis : Caused by mutation in the alpha-actin-1 gene (ACTA1, 102610.0001);
Laboratory abnormalities : Normal or mildly increased serum creatine kinase;
Prefixed ID : #161800;
Origin ID : 161800;
UMLS CUI : C3711389;
Automatic exact mappings (from CISMeF team)
- Broader ORDO disease(s)
- Currated CISMeF NLP mapping
- DO Cross reference
- Genes related to phenotype
- HPO term(s)
- ORDO concept(s)
- Semantic type(s)
- UMLS correspondences (same concept)
