Musculoskeletal abnormalities in a large international cohort of boys with 49,XXXXY

Abstract

49,XXXXY is the rarest X and Y chromosomal variation, with an incidence of 1 in 80,000-100,000 live male births and has been associated with numerous musculoskeletal abnormalities. Data was collected from an international cohort of boys with 49,XXXXY over 10 years. Children were evaluated by a multidisciplinary team consisting of a pediatric orthopedist, a neurogeneticist, a neurodevelopmentalist, and two physical therapists. Increased rates of torticollis (32.4%), hamstring tightness (42%), radioulnar synostosis (67.6%), pes planus (65.2%), and other foot abnormalities (86.9%) were observed. Several anomalies increased with age, specifically hamstring tightness, kyphosis, and scoliosis. The elucidation of the orthopedic profile of this population is necessary in order to provide healthcare providers with current medical information. This research further supports the necessity for the comprehensive multidisciplinary treatment of boys with 49,XXXXY.

Introduction: Comprehensive investigation into an international cohort of boys with 49,XXXXY

“…In addition, this study shows that preschool boys with 49,XXXXY who received early hormonal treatment (EHT) exhibit significantly more intact motor capabilities than those who did not receive testosterone replacement. Tosi et al (2020) described a large cohort of boys with 49, XXXXY and identify numerous musculoskeletal anomalies, including increased rates of torticollis (32.4%), hamstring tightness (42%), radioulnar synostosis (67%) and pes planus (65.2%), some of which are abnormalities also commonly noted in the 47,XXY population Simpson et al, 2003;Tartaglia, Ayari, Howell, D'Epagnier, & Zeitler, 2011). These findings also demonstrate that older 49,XXXXY boys have more hip and knee anomalies than the younger boys.…”

“…Tosi et al (2020) described a large cohort of boys with 49, XXXXY and identify numerous musculoskeletal anomalies, including increased rates of torticollis (32.4%), hamstring tightness (42%), radioulnar synostosis (67%) and pes planus (65.2%), some of which are abnormalities also commonly noted in the 47,XXY population (Samango‐Sprouse et al, 2019; Simpson et al, 2003; Tartaglia, Ayari, Howell, D'Epagnier, & Zeitler, 2011). These findings also demonstrate that older 49,XXXXY boys have more hip and knee anomalies than the younger boys.…”

“…Each article addresses one particular area of interest in relation to the 49,XXXXY phenotype; specifically, neuromotor and neurologic function, musculoskeletal, endocrinological function, speech and language, neurocognition and behavior. Two of the articles, Tosi et al, 2020 and Lasutschinkow et al, 2020, which address the musculoskeletal and behavioral phenotypes of 49,XXXXY respectively, were published ahead of this section and can be found in the online version of this special section. These articles provide evidence of the similar effect of testosterone replacement on the 49,XXXXY population as compared to the 47,XXY population.…”

49,XXXXYsyndrome: A study of neurological function in this uncommon X and Y chromosomal disorder

“…The ULC subtest requires a child to dribble, catch, and throw a tennis ball in multiple tasks. Some of the variation of scores seen in this subtest may be due to the presence of radioulnar synostosis (RUS), which is a documented part of the 49,XXXXY phenotype (Burgemeister et al, 2019;Curfs et al, 1990;Martini et al, 1993;Rehder, Fraccaro, Cuoco, Gimelli, & Porro, 1986;Sprouse et al, 2013;Tosi et al, 2020).…”

“…The ULC subtest requires a child to dribble, catch, and throw a tennis ball in multiple tasks. Some of the variation of scores seen in this subtest may be due to the presence of radioulnar synostosis (RUS), which is a documented part of the 49,XXXXY phenotype (Burgemeister et al, 2019; Curfs et al, 1990; Martini et al, 1993; Rehder, Fraccaro, Cuoco, Gimelli, & Porro, 1986; Sprouse et al, 2013; Tosi et al, 2020). RUS and the associated restrictions in supination and pronation of the elbow may impact activities of daily living (ADL) and tasks that require refined and controlled movements for throwing and catching a ball.…”