Diana Carli1, Maurizio De Pellegrin2, Luisa Franceschi1, Federica Zinali1, Matteo Paonessa3, Simone Spolaore3, Simona Cardaropoli1, Mattia Cravino3, Lorenzo Marcucci2, Antonio Andreacchio4, Nicoletta Resta5, Giovanni Battista Ferrero6, Alessandro Mussa7. 1. Department of Public Health and Pediatric Sciences, University of Torino, Torino, Italy. 2. Pediatric Orthopedic and Traumatology Unit, San Raffaele Hospital, Milan, Italy. 3. Pediatric Orthopedic and Traumatology Unit, Department of Children Health and Cure, Regina Margherita Children Hospital, Città della Salute e della Scienza di Torino, Torino, Italy. 4. Pediatric Orthopedic Department, Buzzi Children's Hospital, Milan, Italy. 5. Medical Genetics, Department of Biomedical Sciences and Human Oncology (DIMO), University of Bari Aldo Moro, Bari, Italy. 6. Department of Public Health and Pediatric Sciences, University of Torino, Torino, Italy; Pediatric Clinical Genetics Unit, Department of Children Health and Cure, Regina Margherita Children Hospital, Città della Salute e della Scienza di Torino, Torino, Italy. 7. Department of Public Health and Pediatric Sciences, University of Torino, Torino, Italy; Pediatric Clinical Genetics Unit, Department of Children Health and Cure, Regina Margherita Children Hospital, Città della Salute e della Scienza di Torino, Torino, Italy. Electronic address: alessandro.mussa@unito.it.
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.
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.
Authors: Maurizio De Pellegrin; Lorenzo Brogioni; Guy Laskow; Graziano Barera; Roberta Pajno; Sara Osimani; Silvia Russo; Lorenzo Marcucci Journal: Children (Basel) Date: 2021-12-07