MYOPATHY, CENTRONUCLEAR, 4; CNM4
CNM4; Centronuclear myopathy type 4
MYOPATHY, CENTRONUCLEAR, 4; CNM4 Is also known as ;Congenital Myopathy With Internal Nuclei And Atypical Cores Is A Rare Genetic Skeletal Muscle Disease Characterized By Neonatal Hypotonia, Distal More Than Proximal Muscle Weakness, Progressive Exercise Intolerance With Prominent Myalgias, And Mild-To-Moderate Overall Motor Impairment With Preserved Ambulation. Face, Extraocular, Cardiac, And Respiratory Muscles Are Unaffected. Mild Cognitive Impairment Is Also Noted In Most Patients.
Related symptoms:
Autosomal dominant inheritance
Generalized hypotonia
Pica
Cognitive impairment
Myopathy
************************************************
The identification of a CCDC78 mutation in a family with congenital myopathy is an important step in terms of bridging the knowledge gap for these disorders, related to both diagnostic assessment and understanding of the disease pathogenesis. A substantial portion of congenital myopathies are genetically unresolved,6 and CCDC78 now represents an excellent new candidate gene for individuals without an identified gene mutation. In particular, CCDC78 may be considered in cases wherein muscle biopsy reveals frequent internal nuclei and/or core-like areas. Future studies are needed to address the possibility of a larger association between CCDC78 mutation and individuals who have congenital myopathies without a known genetic cause. Notably, however, our initial examination suggests that it is unlikely to be a frequent cause of classic CNM.
Am J Hum Genet. 2012 Aug 10; 91(2): 365–371.
doi: 10.1016/j.ajhg.2012.06.012
************************************************************
Synonyms of Centronuclear Myopathy
autosomal dominant centronuclear myopathy (AD-CNM)
Subdivisions of Centronuclear Myopathy
BIN1-related CNM
DNM2-related CNM
RYR1-related CNM
X-linked myotubular myopathy (XLMTM)
In fact, most patients who
have demonstrated clinical MH and who have an RYR1 variant
have no overt clinical phenotype.19–21 Some may even
demonstrate enhanced muscle mass and above average athletic
skills.22 A subset of these phenotypically normal patients
may develop rhabdomyolysis in response to certain conditions
such as heat, exercise, administration of statin medications,
or viral illness.23–32 It is estimated that MH–related
RYR1 pathogenic variants may account for between 20 and
30% of cases of heat- or exercise-induced rhabdomyolysis.4
Some of these patients may demonstrate an elevated baseline
serum creatine kinase level,6
and some may exhibit bleeding
tendencies. 33 Patients without a phenotypic or genotypic
diagnosis that have demonstrated exaggerated or frequent
muscle breakdown under normal or atypical conditions
should be assumed to have an underlying RYR1 pathogenic
variant that confers MH susceptibility, should not receive
anesthetic triggering agents, and should undergo diagnostic
neuromuscular and genetic evaluation
*****************************************************
Mutations in the CCDC78 gene have (August 2012) been reported in one family with a unique form of congenital myopathy with central nuclei. It is important to note that mutations in these genes have been reported in a limited number of patients. Some individuals with a diagnosis of CNM (based upon muscle biopsy results) do not have an identifiable mutation in any of the genes known to be associated with CNM. This may be due to specific mutations that are undetectable by current testing methods, but also suggests that additional, as-yet-unidentified genes may also cause CNM. More research is necessary to fully understand the complex genetics factors associated with CNM.
Comments