Genetic Evaluation of NF1 and Scoliosis Patients
Genetic Evaluation of NF1 and Scoliosis Patients
Neurofibromatosis (NF) is a common genetic disorder that cause tumors to grow along various
 types of nerves and, in addition, can affect the development of bones and skin. It occurs in
 1:4000 persons. NF has been classified into three distinct types: NF1, NF2 and
 Schwannomatosis. NF1 is the focus of this study.

 NF1 is an extremely variable disorder which ranges from extremely mild cases in which the
 only signs of the disorder in adulthood may be multiple café-au-lait spots and a few dermal
 neurofibromas, to more severe cases like disfigurement, scoliosis and learning disabilities.
 Scoliosis (abnormal curvature of the spine) is perhaps the most common bone deformity in NF1
 which usually appears in early childhood. There are two types: dystrophic and non-dystrophic
 scoliosis. Dystrophic scoliosis is usually associated with other bone deformities which are
 seen on x-ray and carries a poorer prognosis than non dystrophic scoliosis. There is evidence
 that genes other than the NF1 gene are responsible for the variable severity of cases. Recent
 studies have identified genetic markers for another condition called adolescent idiopathic
 scoliosis (scoliosis which presents in adolescent age group with no known cause). We believe
 that the same genetic markers may also be present in NF1 patients with scoliosis.

 Our objective is primarily to determine if the same genetic markers discovered in adolescent
 idiopathic scoliosis are also present in NF1 patients with scoliosis.
NF 1 patients with scoliosis can present as either non dystrophic or dystrophic scoliosis.
 Non dystrophic scoliosis behaves and evolves similarly to that of AIS patients. Therefore, we
 hypothesize that Neurofibromatosis type 1 patients with non-dystrophic scoliosis have a
 similar curve progression risk profile markers as patients with Adolescent Idiopathic
 Scoliosis. Dystrophic scoliosis patients will not have the same curve progression risk
 profile as AIS. The long range goal of this study is to possibly develop a genetic test in
 NF1 patients with scoliosis that is predictive of dystrophic or non-dystrophic type. The
 short term goal for the study is to see if the non-dystrophic curves have the same
 single-nucleotide polymorphisms (SNPs') as in AIS and if these SNPs are prognostic.

 One of the goals of this study is to develop and validate a grading scheme to classify
 dystrophic changes in patients with NF 1 scoliosis. Radiographic characteristics of
 dystrophic deformity described by Crawford and Durrani et. al. will distinguish dystrophic
 scoliosis from non-dystrophic scoliosis. In addition, we will be performing genetic testing
 on patients with NF 1 who have had clinical treatment for scoliosis. Although the NF1 gene
 has been identified no specific genetic markers have been identified in NF1 patients with
 scoliosis. Genetic evaluation on a known group of NF1 patients with scoliosis will allow us
 to gain insight as to which phenotypes of NF1 patients would possibly develop spine
 deformities.
Inclusion Criteria:

 -  Diagnosis of Neurofibromatosis type 1 (NIH criteria)[24]

 -  Proper preoperative radiographs of the spine

 -  Spinal fusion done for scoliosis

 -  Age 8 to 65 years old

 Exclusion Criteria:

 -  Paraspinal tumors causing scoliosis

 -  Patients who are unavailable to donate a swab sample for genetic testing will be
 excluded.

 Enrollment Criteria:

 -  In general participants of this study should be NF1 patients with scoliosis who have
 either reached skeletal maturity or required surgical treatment.