A comprehensive 12-year genetic and clinical analysis of unrelated patients with congenital muscular dystrophies (CMDs) in the U.K. has confirmed MDC1A as the the most common CMD subtype, and identified 160 new mutations.
The study, “Congenital muscular dystrophies in the UK population: Clinical and molecular spectrum of a large cohort diagnosed over a 12-year period,” was published in the journal Neuromuscular Disorders.
Congenital muscular dystrophies (CMDs), meaning disorders that are present and detected since birth, are a group of diverse conditions characterized by muscle weakness in the eyes, heart and central nervous system. Information relative to the incidence and prevalence of CMDs in different populations remains scarce.
In the U.K., the Highly Specialised Services (HSS) provides a comprehensive clinical and molecular service for the diagnosis of CMD.
Now, researchers performed a genetic screening for “CMD genes in all the UK patients referred to the two HSS diagnostic laboratories between 2001 and 2013, with the main aim of investigating frequency and relative prevalence of CMD subtypes in the UK population,” they wrote.
Over the 12-year period, a confirmed diagnosis was detected in 440 unrelated patients from 3,734 patient samples sent to HSS, representing 12%. Detailed clinical data was available for 418 patients out of the 440 unrelated patients with mutations.
In the end, 249 of the 418 patients (59.6%) fulfilled the diagnostic criteria for CMD. These were found to carry the typical clinical features of CMD, and so a deeper analysis was restricted to this group.
Researchers found that the most common CMD subtype was laminin-α2 related CMD, also known as MDC1A (37.4%). These results are in agreement with previous studies reporting MDC1A as the most common CMD in other European populations. The second-most common CMD found was dystroglycanopathy (26.5%), followed by Ullrich-CMD (15.7%), and SEPN1 (11.65%) and LMNA (8.8%) gene-related CMDs.
In addition, the most common dystroglycanopathy phenotype was muscle-eye-brain-like disease. Additionally, researchers identified 362 mutations related to CMD, 160 of which were novel. This is particularly important since “more than 2/3 of patients remain genetically undiagnosed,” researchers wrote.
Overall, these results “provide one of the most comprehensive reports on genetics and clinical features of CMD subtypes and should help diagnosis and counseling of families with this group of conditions,” the authors concluded.