Congenital myopathies – Clinical features and frequency of individual subtypes diagnosed over a 5-year period in the United Kingdom

Congenital myopathies

“…The onset of clinical signs was observed predominantly within the first year of life: approximately half of the patients presented in the neonatal period with severe feeding and respiratory complications, as described. [1][2][3][13][14][15]19 Neonatal presentation was more frequently preceded by pregnancy complications, including polyhydramnios and preterm deliveries, compared with a previous study in which only a few neonates were included. 30 Although lethal outcome for a few specific conditions has been reported, 15,17,19,26,27 the relative mortality rate of different CM subgroups has not been investigated.…”

“…Most patients had a genetic diagnosis, with core myopathies and RYR1 mutations, respectively, the most common histopathologic and genetic diagnoses, as reported. 11,13,25 Bearing in mind that the defining features of the CMs (such as FTD, nemaline rods, cores, and central nuclei) are not specific and may occur in other clinical situations, 26 including CNS developmental malformations 27 and recently recognized multisystem disorders with primary autophagy defects, 28,29 we took great care that only patients with clinicopathologic features of a CM without evidence of other underlying conditions were included in this study. The onset of clinical signs was observed predominantly within the first year of life: approximately half of the patients presented in the neonatal period with severe feeding and respiratory complications, as described.…”

“…In particular, failure to thrive and insidious respiratory insufficiency beyond the first year were observed in a substantial proportion, as reported in smaller series. 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.…”

“…5,33 We demonstrated that early-onset scoliosis is common, but usually mild and needing surgery only in 13.6% of all CMs. Half of all patients with scoliosis were ambulant at the time of surgery, suggesting that the development of scoliosis is more determined by early and disproportionate axial weakness 1,3,13 rather than ambulatory state. Scoliosis surgery was overall well tolerated, with preoperative motor abilities and respiratory performance maintained.…”

“…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. Furthermore, genotypephenotype correlations in a subgroup of 99 genetically characterized cases are illustrated.…”