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.
Subject(s)
Chromosomes, Human, X/genetics , Klinefelter Syndrome/diagnosis , Musculoskeletal Abnormalities/diagnosis , Rare Diseases/diagnosis , Adolescent , Child , Child, Preschool , Chromosomes, Human, Y , Flatfoot/complications , Flatfoot/diagnosis , Flatfoot/genetics , Flatfoot/physiopathology , Hamstring Tendons/diagnostic imaging , Hamstring Tendons/physiopathology , Humans , Infant , Klinefelter Syndrome/complications , Klinefelter Syndrome/genetics , Klinefelter Syndrome/physiopathology , Kyphosis/complications , Kyphosis/diagnosis , Kyphosis/genetics , Kyphosis/physiopathology , Male , Musculoskeletal Abnormalities/complications , Musculoskeletal Abnormalities/genetics , Musculoskeletal Abnormalities/physiopathology , Radius/abnormalities , Radius/physiopathology , Rare Diseases/complications , Rare Diseases/genetics , Rare Diseases/physiopathology , Scoliosis/complications , Scoliosis/diagnosis , Scoliosis/genetics , Scoliosis/physiopathology , Synostosis/complications , Synostosis/diagnosis , Synostosis/genetics , Synostosis/physiopathology , Torticollis/complications , Torticollis/diagnosis , Torticollis/genetics , Torticollis/physiopathology , Ulna/abnormalities , Ulna/physiopathologyABSTRACT
49, XXXXY is a rare aneuploidy and variant of Klinefelter syndrome, occurring in 1 per 80,000-100,000 live births. We present a cohort of 40 affected males, focusing on musculoskeletal problems. Subjects were participants in an annual 49er family support group meeting. Children were examined in a multidisciplinary clinic by a pediatric neurologist and geneticist, a pediatric orthopedist, a neurodevelopmentalist, and two physical therapists. The patient data were collected from this clinic from 2004 to 2012. All patients were required to have karyotypes that confirmed the presence of XXXXY. There was a high prevalence of musculoskeletal disorders, particularly hypotonia (34 patients [85%]), radioulnar synostosis (30 [75%]), pes planus (26 [65%]), asymmetric hip rotation (27 [67.5%]), and clinodactyly (24 [60%]). Other, less common lower-extremity disorders, included, 5 patients (12.5%) with unilateral club foot, 5 boys (12.5%) with pes cavus, 10 patients (25%) genu valgum and 2 children with genu varus (5%). To our knowledge, this is the first large cohort of boys with 49, XXXXY that focuses on musculoskeletal disorders. There was an increased incidence of hypotonia, clubfoot, avascular necrosis of the femoral head, radioulnar synostosis, and pes planus compared to the normative population. Boys with 49, XXXXY would benefit from multidisciplinary evaluations, particularly from pediatric orthopedists, physical therapists, neurologists, and geneticists for appropriate medical care.
