Toe walking in children with variants in myopathy-associated genes: A retrospective descriptive cohort study.

BACKGROUND

Tip-toe walking may occur in children carrying variants associated with, neuromuscular disorders, but characteristics of children carrying variants in selected, muscle-related genes remain insufficiently characterized. We characterized children, with tip-toe walking carrying variants in CAV3, CLCN1, COL6A2, or COL6A3.

METHODS

This retrospective study included children assessed at a referral center, between November 2022 and June 2026. Clinical and genetic data were reviewed from, a 49-gene next-generation sequencing panel. Demographic, developmental, toewalking, caregiver-reported, and clinical characteristics were summarized descriptively.

RESULTS

The cohort comprised 288 children carrying variants in CAV3, CLCN1, COL6A2, or COL6A3. Demographic characteristics, age at independent walking, age, at onset of tip-toe walking, tip-toe walking proportion, and clinical course were, comparable across cohorts. Independent walking occurred at 12-13 months, while tiptoe, walking began during the second year of life and accounted for approximately 80%, of daily walking. Family history of tip-toe walking was reported in one-third to one-half, of participants. Pain, cramps, fatigue, and speech difficulties were reported across all, cohorts. Restricted ankle mobility was consistently documented, while pes cavus, littlefinger, shortening/curvature, and chest wall abnormalities were frequent. VUS, predominated in CAV3, COL6A2, and COL6A3.

CONCLUSIONS

Children carrying variants in these four genes showed similar tip-toe, walking characteristics. Additional findings occurred in a minority. Findings should be, interpreted within the limitations of the retrospective, single-center design, unequal, cohort sizes, reliance on caregiver-reported and observational data, limited, segregation analysis, and predominance of VUS in three cohorts. Results do not.