“Introduction. The VonWillebrand Factor-A domain containing-1-protein gene (VWA1) encodes an extracellular matrix protein expressed in both muscle and peripheral nerve, where it interacts with collagen-VI and perlecan. Recently, biallelic loss of function variants of VWA1 have been associated with a novel form of slow-progressing neuromyopathy characterized by child- to adult-onset and primarily affecting lower limbs.
Case Presentation. A 16-year-old female presented with HyperCKemia(3-4X UNV), recurrent falls, and myalgias. She had an unremarkable family history; she was born with equino-cavus foot deformity and began toe-walking at 12 months of age due to bilateral Achilles tendon retractions. Myalgias and falls presented at age 6, with scoliosis developing in adolescence. Neuromuscular examination confirmed pes cavus, ankle retractions, mild scoliosis-lumbar hyperlordosis, and mid-distal thigh hypotrophy, with overall preserved strength and sensitivity. EMG did not evidence specific diagnostic patterns and cardiac- pulmonary assessments displayed normal. At 16, quadriceps muscle biopsy indicated a dystrophic pattern with beta-sarcoglycan deficiency, without identified variants of SGCB gene in muscle tissue. Sequential muscle MRIs revealed a progressive diffuse involvement of the quadriceps over time with a sandwich-like pattern, while sparing the sartorius, gracilis, and leg muscles. The condition only mildly progressed; at 29 years, a NGS panel identified a homozygous pathogenic variant c.62_71dup(p.Gly25ArgfsTer74) in the VWA1 gene, leading to a recently described form of neuromyopathy.
Conclusions. Long-standing unsolved cases should undergo reanalysis over time as genetics advance, and new interesting pathogenetic features can emerge. In our case, the VWA1 mutation presented strong clinical and MRI analogies with other extracellular matrix protein defects.”