Clinical Features in Children with Persistent Toe Walking Who Carry Heterozygous PYGM Variants: A Cross-Sectional Study.

OBJECTIVES

Persistent toe walking (TW) in children is often idiopathic but may conceal subtle neuromuscular or metabolic causes. This cross-sectional, retrospective study investigated clinical and genetic characteristics of children carrying PYGM variants to explore potential subclinical phenotypes among heterozygous carriers.

METHODS

Seventy-two (72) children meeting criteria for idiopathic TW were evaluated using a standardized clinical protocol and a validated 49-gene next-generation sequencing neuromuscular panel. Variants were classified as pathogenic, likely pathogenic, or of uncertain significance according to ACMG/AMP guidelines. Analyses were descriptive.

RESULTS

Among 1,300 screened patients, 72 were identified as PYGM variant carriers. Toe walking was bilateral in all cases, with severe dorsiflexion restriction (≤ 5°) in 80.5%. Pes cavus was observed in 93% of patients, and muscle symptoms-pain, fatigue, or cramps-occurred in approximately one-third. VUS carriers displayed comparable, slightly milder muscle symptom frequencies than P/LP carriers. 12.5% could perform heel walking. Speech difficulties were reported in 56.9% of cases.

CONCLUSIONS

While causality cannot be inferred, these findings suggest that heterozygous PYGM variants may contribute to subtle neuromuscular phenotypes. Genetic testing can be considered in persistent TW when clinical findings raise suspicion for an underlying neuromuscular/metabolic condition.