Evolution over Time of Leg Length Discrepancy in Patients with Syndromic and Isolated Lateralized Overgrowth

Abstract

Objective: To provide information on evolution over time of leg length discrepancy in patients with syndromic and isolated lateralized overgrowth.

Study design: This retrospective study investigates leg length discrepancy longitudinally in 105 patients with lateralized overgrowth either isolated (n = 37) or associated with Beckwith-Wiedemann spectrum (n = 56) or PIK3CA-related overgrowth spectrum (n = 12). Discrepancy was measured by standard methods and categorized as minor, mild, severe, and critical, based on the thresholds of 1, 2 and 5, respectively.

Results: The period of observation from diagnosis was 1.7 ± 2.6 to 9.0 ± 6.0 years. Leg length discrepancy was 11.0 ± 7.2 mm at diagnosis and 17.1 ± 14.4 mm at last visit. Both final leg length discrepancy and change over time were correlated with discrepancy at diagnosis (r² = 0.45, P < .001 and r² = 0.05, P = .019, respectively). Among minor leg length discrepancy at diagnosis, 47.5% remained minor, 40.0% become mild, and 12.5% severe. Among patients with discrepancy classified as severe at diagnosis, 84.6% remained severe and 15.4% evolved to critical. The isolated lateralized overgrowth group showed a milder evolution over time compared with Beckwith-Wiedemann spectrum and PIK3CA-related overgrowth spectrum groups. Among patients with Beckwith-Wiedemann, those with paternal chromosome 11 uniparental disomy had more severe leg length discrepancy at diagnosis and evolution over time.

Conclusions: Leg length discrepancy associated with isolated or syndromic lateralized overgrowth tends to worsen with growth and correlates with discrepancy at first observation. Among the genotypic groups, isolated lateralized overgrowth tends to have a milder evolution, whereas Beckwith-Wiedemann spectrum predisposes to a more severe outcome, especially if associated with paternal chromosome 11 uniparental disomy genotype.

Keywords: Beckwith-Wiedemann syndrome; hemihyperplasia; hemihypertrophy; lateralized overgrowth; leg length discrepancy; overgrowth.