Congenital myopathies in the adult neuromuscular clinic

Abstract

ObjectiveTo investigate the spectrum of undiagnosed congenital myopathies (CMs) in adults presenting to our neuromuscular clinic and to identify the pitfalls responsible for diagnostic delays.MethodsWe conducted a retrospective review of patients diagnosed with CM in adulthood in our neuromuscular clinic between 2008 and 2018. Patients with an established diagnosis of CM before age 18 years were excluded.ResultsWe identified 26 patients with adult-onset CM and 18 patients with pediatric-onset CM who were only diagnosed in adulthood. Among patients with adult onset, the median age at onset was 47 years, and the causative genes were RYR1 (11 families), MYH7 (3 families) and ACTA1 (2 families), and SELENON, MYH2, DNM2, and CACNA1S (1 family each). Of 33 patients who underwent muscle biopsy, only 18 demonstrated histologic abnormalities characteristic of CM. Before their diagnosis of CM, 23 patients had received other diagnoses, most commonly non-neurologic disorders. The main causes of diagnostic delays were mildness of the symptoms delaying neurologic evaluation and attribution of the symptoms to coexisting comorbidities, particularly among pediatric-onset patients.ConclusionsCMs in adulthood represent a diagnostic challenge, as they may lack the clinical and myopathologic features classically associated with CM. Our findings underscore the need for a revision of the terminology and current classification of these disorders.

Filamentous tangles with nemaline rods in MYH2 myopathy: a novel phenotype

“…2-Hz repetitive stimulation of the facial, spinal accessory and peroneal nerves showed no decrement. (Limited information on this patient were reported prior to the pathological characterization of the myopathy [ 17 ]).…”

Myopathies with finger flexor weakness: Not only inclusion‐body myositis

“…Subsequent studies have expanded both the clinical and histological spectrum of ACTA1 ‐myopathy 49–51 . Although ACTA1 ‐myopathy is classified as a congenital myopathy, some patients present in late childhood or adulthood 52 . Most display predominantly proximal weakness, but families have been described with scapuloperoneal, finger extensor, or finger flexor weakness 53,54 .…”

“…sIBM frequently features a combination of short‐ and long‐duration motor unit potentials, as well as fibrillation potentials, positive sharp waves, and myotonic discharges 113 . However, mixed motor unit potentials may also be observed in many other chronic myopathies, 52 and can be particularly frequent in ACTA1 ‐myopathy, leading to misdiagnosis of a neurogenic process 51,53 . Myotonic discharges are nearly universal in DM1, but clinical and even electrical myotonia can be subtle or lacking in DM2 114,115 .…”

Muscle biopsy: what and why and when?

“…24 26 Some myopathies that cause non-traumatic exertional rhabdomyolysis are not included in such a panel, for example, muscle dystrophies (case 2), ryanodine receptor myopathies and mitochondrial disorders. 27–29 Clinicians should seek relevant clinical clues when reviewing patients following their crisis. The indications for biopsy in these circumstances will then be similar to those when suspecting a dystrophy or a mitochondrial disorder (outlined above).…”