Expanding the clinical and genetic spectrum of biallelic MYO18B pathogenic variants in congenital myopathy.

MYO18B is an unconventional class XVII myosin that is predominantly expressed in muscle and heart tissue. Recessive pathogenic MYO18B variants cause a rare myopathy associated with Klippel-Feil syndrome (KFS), facial dysmorphism, short stature and less frequently cardiomyopathy. Reported neuromuscular manifestations were variable, with nemaline bodies observed in one patient. We report six novel patients from four families with an early onset myopathy due to biallelic MYO18B variants. Facial, axial, proximal upper and lower limb weakness was prevalent. Three patients had congenital findings including hip dislocation, reduced fetal movements and arthrogryposis with generalized hypotonia. Marked intrafamilial variability of muscle involvement was noted in two siblings. Short stature was present in three patients, ptosis and facial dysmorphisms in two, respectively. KFS was radiologically noted in one patient. Cardiac involvement was absent. Lower limb MRI revealed selective involvement of semitendinosus and tibialis anterior muscles. The clinical myopathic findings were supported in two patients by myopathic histological features including fiber size variation, type I fiber predominance and core pathology, without any detectable nemaline bodies. Our cases highlight the variable presentation and intrafamilial variability and first report selective muscle MRI involvement in this condition, adding on the limited literature on patients with MYO18B gene myopathy.