Toe Walking: A Descriptive Comparison of Clinical Characteristics Across Sensorimotor and Sensory Neuropathy-Associated Genes

Background Persistent toe walking has been associated with variants in numerous neuropathy-associated genes, although clinical findings among children carrying variants in genes associated with sensorimotor and sensory neuropathies remain insufficiently characterized. This study descriptively characterized and compared clinical findings across these two gene categories. Methods This retrospective descriptive study included 1,054 children with persistent toe walking in whom 1,121 variants were identified across 30 neuropathy-associated genes using a targeted next-generation sequencing panel. Genes were categorized as sensorimotor (27 genes) or sensory (3 genes) according to their predominant neuropathy phenotype. Demographic characteristics, toe-walking history, reported symptoms, developmental features, and neurological and musculoskeletal findings were analyzed descriptively across gene cohorts. Results Variants of uncertain significance predominated in both neuropathy categories. POLG and TRPV4 contained comparatively higher proportions of likely pathogenic and pathogenic variants. Clinical findings showed substantial overlap across the two categories. Mean age at assessment, age at independent walking, toe-walking onset, daily toe-walking proportion, clinical course, and family history showed similar ranges. Muscle pain, cramps, speech difficulties, and balance impairment were observed across sensory gene cohorts, while their frequencies varied more widely across sensorimotor gene cohorts. Conversely, the highest reported frequencies for heel walking, back abnormalities, visual disturbances, fatigue, and pigeon chest occurred in individual sensorimotor gene cohorts. Pes cavus and shortening of the little finger were observed across both categories. Conclusions Descriptive findings showed clinical overlap across children carrying variants in sensorimotor and sensory neuropathy-associated genes.