Genetic Evaluation of NF1 and Scoliosis Patients

Genetic Evaluation for the Scoliosis Gene(s) in Patients With Neurofibromatosis 1 and Scoliosis

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.

Study Overview

• Status: Completed
• Conditions: Scoliosis; Neurofibromatosis 1
• Intervention / Treatment: Other: Cheek swab

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.

• Study Type: Observational
• Enrollment (Actual): 59

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55454
      • University of Minnesota

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 65 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Dystrophic Scolisis and NF1; Patients with NF1 diagnosed with dystrophic scoliosis that have been clinically treated will be asked for a cheek swab for genetic testing	Other: Cheek swab; 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.
Non-dystrophic scoliosis and NF1; NF1 patients with non-dystrophic scoliosis that have been treated clinically. will be asked for a cheek swab for genetic testing	Other: Cheek swab; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SCOLISCORE	The SCOLISCORE Test is the first and only genetic test proven to give physicians and parents insight into the possible progression of patient with Adolescent Idiopathic Scoliosis (AIS), thereby reducing the uncertainty of AIS progression.	1 month after sample submission

Collaborators and Investigators

• Sponsor: University of Minnesota
• Collaborators: Mayo Clinic; Columbia University; University of Utah; Texas Scottish Rite Hospital for Children; Norton Leatherman Spine Center; Children Hospital Cincinnati OH
• Investigators: Principal Investigator: David W Polly, MD, University of Minnesota, Orthopaedic Surgery

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (ACTUAL): August 1, 2015
• Study Completion (ACTUAL): August 1, 2015

Study Registration Dates

• First Submitted: November 13, 2012
• First Submitted That Met QC Criteria: January 22, 2013
• First Posted (ESTIMATE): January 25, 2013

Study Record Updates

• Last Update Posted (ACTUAL): November 1, 2019
• Last Update Submitted That Met QC Criteria: October 30, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Scoliosis; Neurofibromatosis Type One
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Genetic Diseases, Inborn; Musculoskeletal Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Neoplasms, Nerve Tissue; Peripheral Nervous System Diseases; Nervous System Neoplasms; Spinal Diseases; Bone Diseases; Heredodegenerative Disorders, Nervous System; Neoplastic Syndromes, Hereditary; Spinal Curvatures; Nerve Sheath Neoplasms; Neurocutaneous Syndromes; Peripheral Nervous System Neoplasms; Scoliosis; Neurofibromatoses; Neurofibromatosis 1; Neurofibroma
• Other Study ID Numbers: 0804M30543

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO