Consensus Statement on Standard of Care for Congenital Myopathies

Abstract

Recent progress in scientific research has facilitated accurate genetic and neuropathological diagnosis of congenital myopathies. However, given their relatively low incidence, congenital myopathies remain unfamiliar to the majority of care providers, and the levels of patient care are extremely variable. This consensus statement aims to provide care guidelines for congenital myopathies. The International Standard of Care Committee for Congenital Myopathies worked through frequent e-mail correspondences,

Congenital myopathies

“…5,[13][14][15]19 It is often thought that children with CMs who achieve independent ambulation usually do not lose this ability later. 4 However, intermittent wheelchair use was needed in 22% of our ambulant patients, whereas 9% became completely wheelchairdependent within a few years, supporting observations of deterioration in muscle strength after the achievement of ambulation. 32 All patients who lost ambulation were late walkers; this may suggest that ambulatory loss reflects the additional effects of increased height/weight on already substantially compromised muscle power, rather than a progressive loss of muscle strength.…”

“…The need for comprehensive data regarding functional abilities, cardiorespiratory involvement, orthopedic complications, and survival, as a basis for anticipatory patient management and planning of future therapeutic trials, has been recently highlighted. 4 The natural history of specific subgroups has been described in only a few cohorts, not all of which had been fully genetically characterized. 5,[13][14][15][16][17][18][19] Herein, we report the clinical course of 125 patients with CM, reviewed at a single neuromuscular center.…”

Insights into the effects of disease‐causing mutations in human actins

“…One focus of these studies has been the set of mutations in human a-skeletal muscle actin that cause nemaline myopathy (NM). For the most part, this is a congenital disease generally caused by mutations in proteins that constitute the contractile apparatus or those whose function is to control contraction [North et al, 1997;Sanoudou and Beggs, 2001;Sparrow et al, 2003;Clarkson et al, 2004;Nowak et al, 2007;Wang et al, 2012]. Affected individuals display muscle weakness and poor muscle tone along with respiratory problems, and severity of symptoms can range over a wide spectrum.…”

“…Histologically, muscle cells from affected patients display rods or threads of aggregated protein. About 20% of NM cases arise from these actin mutations which are spread over the entire actin surface [North et al, 1997;Sanoudou and Beggs, 2001;Wang et al, 2012].…”

“…Histologically, muscle cells from affected patients display rods or threads of aggregated protein. About 20% of NM cases arise from these actin mutations which are spread over the entire actin surface [North et al, 1997;Sanoudou and Beggs, 2001;Wang et al, 2012].One set of studies designed to assess the effects of these mutations on actin function involved cloning a series of ten of these mutations in the Drosophila Act88F gene. These occurred at four different residues, A138 and R372 near the barbed end of the actin monomer and G268 and R256 in subdomain 4 near the strand-strand interface.…”