Orthopaedic conditions in Ras/MAPK related disorders.

Abstract

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.

• Authors: Kent A Reinker, David A Stevenson, Ann Tsung
• Journal: Journal of pediatric orthopedics (J Pediatr Orthop) Vol. 31 Issue 5 Pg. 599-605 ( 2011) ISSN: 1539-2570 [Electronic] United States
• PMID: 21654472 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Protein Tyrosine Phosphatase, Non-Receptor Type 11

Topics

• Abnormalities, Multiple (genetics)
• Adolescent
• Arnold-Chiari Malformation (complications, genetics)
• Child
• Child, Preschool
• Ectodermal Dysplasia (complications, genetics)
• Facies
• Failure to Thrive (complications, genetics)
• Female
• Genes, ras (genetics)
• Heart Defects, Congenital (complications, genetics)
• Humans
• Incidence
• Infant
• LEOPARD Syndrome (complications, genetics)
• MAP Kinase Signaling System (genetics)
• Male
• Musculoskeletal Diseases (epidemiology, etiology, genetics)
• Mutation
• Noonan Syndrome (complications, genetics)
• Protein Tyrosine Phosphatase, Non-Receptor Type 11 (genetics)
• Risk Factors
• United States (epidemiology)