Resolving a Multi-Generational Neuromuscular Mystery in a Family Presenting with a Variable Scapuloperoneal Syndrome in a c.464G>A, p.Arg155His VCP Mutation

Valosin containing protein (VCP) mutations have been reported to present with a high degree of variability and can be present in patients even if they may have an initial normal work up. A 55-year-old woman was labeled as “normal” and “pain medication seeking” after an unrevealing work up of clinical, laboratory, electrodiagnostic, radiographic, pathologic, and genetic testing. She continued to present with chronic neck pain, and had variable features of scapuloperoneal atrophy, which was also seen in her family. The patient and her family were found to have a known pathogenic c.464G>A, p.Arg155His (R155H) mutation in the VCP gene. Despite traditional thinking of attempting to localize neurological syndromes, VCP mutations are difficult to localize as they can present with significant clinical heterogeneity including a scapuloperoneal syndrome with variable neuropathic and myopathic features.

Scapular Winging

Scapulae play a central role in arm abduction, and their failure causes poor abduction despite preserved arm abductors (deltoids and supraspinati). A good knowledge about the anatomy of the scapulae and their muscles and nerves is necessary. Unilateral winging is usually due to nerve pathology, but frank asymmetry is typical for facioscapulohumeral muscular dystrophy (FSHD). Progressive bilateral scapular winging is seen in many myopathies, including muscular dystrophy (MD) and scapuloperoneal syndrome (SPS). Weakness of different scapular muscles leads to different scapular positions during arm movement. When the underlying disease is not treatable, surgical fixation of the scapulae on the chest wall improves arm abduction.

Distal Leg Weakness

Plantar flexion and extension weakness are usually neuromuscular in nature. Rarely, focal foot dystonia, ankle arthritis, and spasticity lead to diagnostic confusion. Painful, sequential foot drop is a common feature of vasculitis. Preserved extensor digitorum brevis (EDB) bulk in the face of foot drop is a feature of myopathy. Progressive, painless weakness of the foot flexion and extension with normal sensation and brisk deep tendon reflexes (DTRs) are typically seen in amyotrophic lateral sclerosis (ALS). In patients with chronic, bilateral foot drop, examination of the scapulae is essential to rule out scapuloperoneal syndrome and facioscapulohumeral muscular dystrophy (FSHD). In inflammatory neuropathies, distal leg weakness is the last to respond to therapy, and some residual deficit is common.

THE CLINICAL CASE OF STARK–KAESER TYPE SCAPULOPERONEAL SYNDROME

We present a rare case of Stark–Kaeser type scapuloperoneal syndrome type with mild weakness and hypotrophy in proximal limb, with rough paresis of feet, walking dysfunction and slowly-progressive course. The article briefly describes current views on the etiology and pathogenesis of this disease. The case is of interest to physicians of various specialties for the differential diagnosis of inherited neuromuscular disorders.

Distal Leg Weakness

Plantar flexion and/or extension weakness is usually neuromuscular in nature. Rarely, focal foot dystonia, ankle arthritis, and spasticity lead to diagnostic confusion. Painful sequential foot drop is a common feature of vasculitis. Preserved EDB bulk in the face of foot drop is a feature of myopathy. Progressive painless weakness of the foot flexion and extension with normal sensation and brisk deep tendon reflexes are typically seen in ALS. In patients with chronic bilateral foot drop, examination of the scapulae is essential to rule out scapuloperoneal syndrome and FSHD. In inflammatory neuropathies, distal leg weakness is the last to respond to therapy and some residual deficit is common.