A Mild But Typical Presentation of Bethlem Myopathy With a Novel In-Frame Deletion in COL6A1

In the era of low-threshold exome sequencing, deep phenotyping is losing popularity.We report on a family, in which the description of symptoms was crucial for diagnosis finding.A sister and brother sought medical attention for Achilles tendon contractures due to suspected "spasticity" (Figure).Initial commercial exome sequencing analyses were reported as "negative."However, precise phenotyping revealed additional, pathognomonic elbow and long finger flexor contractures and mild proximal muscle weakness.There were abnormal truncal pendulum movements when walking (Video 1).Subjectively, the mother was healthy but had the same phenotype.After the identification of myopathic findings on MRI, electromyography and elevated creatine kinase, the exome data were reanalyzed.This revealed a novel heterozygous in-frame deletion at the COL6A1 locus in all patients, but not in the unaffected father.This variant had not been published in the gnomAD database of the general population.We diagnosed a mild, but typical presentation of Bethlem myopathy. 1,