Anti-MYOT monoclonal antibody Made to order

A 52-year-old man noted distal dominant slowly progressive muscle weakness at age 36 years. On muscle CT, the red muscles of the soleus, anterior tibial and paraspinal muscles, where type 1 fiber is known to predominate, were almost totally replaced by fat tissue while quadriceps femoris, gastrocnemius and upper extremity muscles were relatively spared. Quadriceps muscle biopsy revealed multi-minicores in addition to occasional larger cores, in about 70% of the type 1 fibers. A novel heterozygous nucleotide change c.5869T > A (p. S1957T) was identified in RYR1. Although pathogenicity was not confirmed, this nucleotide change was absent in 100 control DNA. We did not find a mutation in either multi-minicore disease-associated gene, SEPN1, or major distal myopathy-related genes, including GNE, ZASP, MYOT, exons 32-36 of MYH7, and the last exon of TTN. This is probably a unique form of distal myopathy characterized by the presence of multi-minicores with preferential involvement of type 1 fibers.

Left ventricular hypertrabeculation/noncompaction is a myocardial abnormality of unknown etiology/pathogenesis, which is frequently associated with neuromuscular disorders or chromosomal defects. LVHT in association with a MYOT mutation has not been reported. The patient is a 72-year-old male with a history of strabismus in childhood, asymptomatic creatine-kinase elevation since age 42 years, slowly progressive lower limb weakness since age 60 years, slowly progressive dysarthria and dysphagia since age 62 years, and recurrent episodes of arthralgias and myalgias since age 71 years. He also had arterial hypertension, diverticulosis, hyperlipidemia, coronary heart disease, and a hiatal hernia with reflux esophagitis. Clinical exam revealed mild quadruparesis and proximal wasting of the legs. Whole exome sequencing revealed a known variant in the MYOT gene. Muscle biopsy, previously assessed as inclusion body myopathy, was compatible with the genotype after revision. Cardiologic work-up revealed a left anterior hemiblock, mild myocardial thickening, and noncompaction. This case shows that myotilinopathy may manifest as a multisystem disease, including noncompaction.