Background: The RAS/MAPK disorders [Noonan syndrome, cardiofaciocutaneous (CFC) syndrome, Costello syndrome, and Leopard syndrome] are heterogenous conditions with phenotypic overlap. Their orthopaedic manifestations are not well defined, and their phenotypic similarity makes differentiating them difficult.
Methods: We prospectively evaluated 60 individuals: 26 with Noonan syndrome, 32 with CFC syndrome, and 2 with Costello syndrome. Each individual underwent a structured orthopaedic history and physical evaluation by an orthopaedic surgeon, and a syndromic evaluation by a geneticist.
Results: All groups had a high prevalence of scoliosis (8/26 Noonan syndrome, 8/32 CFC syndrome, and 1/2 Costello). Those with Noonan syndrome or CFC syndrome had a high instance of serious cervical spine disorders, including cervical stenosis, Arnold-Chiari malformation, and syringomyelia in the Noonan syndrome individuals and hydrocephalus, cervical stenosis, torticollis, and Arnold-Chiari in the CFC syndrome individuals. Noonan syndrome manifestations included chronic pain (n=21), pes planus (n=11), pes cavus (n=5), hip contractures (n=5), hand dysfunction (n=3), and hip dysplasia (n=2). Manifestations of CFC syndrome included pes planovalgus (n=20), knee flexion contractures (n=7), hip dysplasia (n=5), elbow flexion contractures (n=4), pedal calluses (n=4), toe crowding (n=4), and hip contractures (n=4). Individuals with Costello syndrome had shorter stature than the other groups and were prone to have hand contractures.
Conclusions: Orthopaedic manifestations are frequent and diverse in Ras/MAPK disorders and can be used in phenotypic differentiation between these disorders.
Level of Evidence: II.
*Department of Orthopaedics, University of Texas Health Sciences Center, San Antonio, TX
†Division of Medical Genetics, Department of Pediatrics, University of Utah, Salt Lake City, UT
Reinker received support for lodgings from CFC International. Stevenson received grant support from a Doris Duke Charitable Foundation Clinical Scientist Development Award. No other support was obtained.
Reprints: Kent A. Reinker, MD, 13637 Bluff Circle Street, San Antonio, TX 78216. e-mail: firstname.lastname@example.org.