Neurofibromin in Skeletal Development [chapter]

Mateusz Kolanczyk, David A. Stevenson
2015 Molecular Genetics of Pediatric Orthopaedic Disorders  
Skeletal complications are frequent in neurofibromatosis type 1 (NF1). Various skeletal manifestations are observed including generalized osteopenia (low bone mass), scoliosis, long bone bowing, pseudarthrosis, bone lytic lesions, and sphenoid wing dysplasia. Historically, focal skeletal lesions in NF1 were suspected to be caused by nearby localized tumors. However, genetic experiments have brought an entirely new view of NF1 musculoskeletal pathology, illustrating the power of gene discovery
more » ... d genetic model systems. We now appreciate that neurofibromin is required for normal musculoskeletal system development. We now understand that NF1 bone dysplasia can be caused by loss of function mutations in NF1, occurring in the mesenchymal lineage, rather than through tumor influence as previously thought. This is not to say that the presence of tumors has no impact on the bone. It is likely that tumors can impact bone tissue and further exacerbate pathological processes. Here we review the current state of knowledge of neurofibromin in bone and skeletal muscle. We outline mechanisms underlining NF1 musculoskeletal dysplasias derived from both mouse disease models and observations of human NF1 pathology. We also discuss pathways regulated downstream of NF1 and their potential impact on the musculoskeleton.
doi:10.1007/978-1-4939-2169-0_2 fatcat:6sczernrsrfajdmjg6pb6s4zga