Effects of Physical Training on Bone and Muscle Quality, Muscle Strength, and Motor Coordination in Children With NF1

Disorders of the Ras pathway have significant phenotypic overlap and include Noonan syndrome,
CFC syndrome, Legius syndrome, Costello syndrome and neurofibromatosis type 1 (NF1). NF1 is
one of the most common genetic disorders presenting in childhood with an incidence of 1/3000.
NF1 is associated with skeletal abnormalities such as short stature, scoliosis, and long bone
fracture with non-union. We recently reported that children with NF1 have abnormalities of
bone and muscle architecture as evidenced by decreased bone mineral density, decreased bone
strength, and low muscle mass, all of which may predispose them to fractures and scoliosis
(Stevenson et al., 2005, 2007, 2009). Our preliminary data show that children with NF1 have
poor motor coordination and muscle strength, potentially secondary to abnormal neuromotor
learning. We hypothesize that poor motor coordination and decreased muscle strength
contribute to the osteopenia in NF1. Our objective is to identify effective and non-invasive
strategies to improve motor coordination, muscle strength, and bone and muscle architecture
in children with disorders of the Ras pathway, in hopes of decreasing fractures and improving
physical activity levels. Plyometric physical training consists of quick, high-intensity,
weight-bearing movements, and is an encouraging intervention for use in these children.

Inclusion Criteria:

- Fulfill NIH clinical diagnostic criteria

Exclusion Criteria:

- Visual impairment

- Participation in a simultaneous medical intervention trial

- Orthopedic procedure within the last 6 months.

- Pregnancy

- Home location greater than 3-4 hours drive time from Shriners Hospital

- Tibial pseudarthrosis