Genetic Evaluation of NF1 and Scoliosis Patients
Condition: Neurofibromatosis 1; Scoliosis
MeSH terms: Neurofibromatoses; Neurofibromatosis 1; Neurofibroma; Scoliosis
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Cheek swab
Intervention type(s): Other
Intervention description(s): Participants will be asked to give us a swab (a long Q-tip) of the inside of your cheek (inside your mouth) for genetic testing. This should take no more than 10 seconds. It will not hurt. The swab kit will be provided by Affiliated Genetics. It will include a self-addressed stamped envelope to mail the swab back to Affiliated Genetics. Participants existing x-rays will be reviewed as part of this study as well. We will review participant's medical record to look at what treatments have been executed during the course of participation. Once the individual agrees to participate in this project their private health information will be sent to Axial Biotech Inc., the company that will be doing the genetic testing.
Observational model: Cohort
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        Candidates will be identified by spine surgeons who are members of the Spinal Deformity
        Study Group. Participants need to be age 8 to 65 years old. These will be individuals who
        have been clinically diagnosed with NF 1 and have undergone spinal fusion for scoliosis
        (either dystrophic or non-dystrophic). The participating physicians will explain the
        research to qualifying patients or their guardians. We have added a flyer for the
        participating physicians to hand out to their patients. The patient/guardian may then take
        this flyer home and contact study personnel directly, thus removing the participating
        physician and/or his staff from the process.
      
Biospecimen description: 
      Participants will be asked to give us a swab (a long Q-tip) of the inside of your cheek
      (inside your mouth) for genetic testing. This should take no more than 10 seconds. It will
      not hurt. The swab kit will be provided by Axial Biotech Inc. It will include a
      self-addressed stamped envelope to mail the swab back to Axial Biotech Inc. Participatns
      existing x-rays will be reviewed as part of this study as well. We will review participant's
      medical record to look at what treatments have been executed during the course of
      participation. Once the individual agrees to participate in this project their private health
      information will be sent to Axial Biotech Inc., the company that will be doing the genetic
      testing.
    
Keywords: Neurofibromatosis Type One; Scoliosis