Spots Global Cancer Trial Database for Study of Disease Severity in Adults With Neurofibromatosis Type 1 (NF1)

Study Description

Brief Summary: This study may identify genes that predict the seriousness of neurofibromatosis type 1 (NF1). Finding these genes may explain why some people with NF1 have more medical problems than others. The study will also examine medical problems in NF1 that are rarely seen and are not well understood. Male and female patients with NF1 who have gone through puberty may be eligible for this study, as well as patients of any age who have unique or under-recognized disease features. Affected and unaffected family members, including parents, siblings, and more distant relatives, may also be enrolled. Candidates are screened with a discussion of medical history or review of medical records, or both. Participants undergo the following procedures: Patients with NF1 * Physical examination and family history * Photographs of the iris of each eye * Photographs of the back, abdomen and thigh to count skin tumors * Photographs of the face and body (with underwear on) to help track growth and appearance * Magnetic resonance imaging (MRI) of the spine (This test uses a magnetic field and radio waves to look for tumors and curvature of the spine. The patient lies still in the scanner, a narrow cylindrical device, wearing earplugs to muffle loud knocking sounds that occur during the scan. A contrast material called gadolinium is injected into a vein through a catheter to enhance the images.) * Blood draw for genetic studies * Possibly a skin biopsy (with the use of numbing medicine, removal of a small sample of skin tissue) to grow cells in the laboratory Patients with NF1 who have unique or under-recognized disease features * Physical examination and family history * Blood draw for genetic studies * Possibly a skin biopsy * Possibly additional tests, such as blood work, x-rays, photographs, MRIs, ultrasounds, or other tests Unaffected family members * Blood draw for genetic studies * Brief skin and eye examinations * Possibly a skin biopsy for cell culture Families are asked to give permission for researchers to recontact them for follow-up information, additional blood samples, or follow-up visit.

Detailed Description: We hypothesize that normal germline variation in gene expression accounts, in part, for variation in the clinical severity and phenotype of the monogenic disorder neurofibromatosis type 1 (NF1). The phenotype of NF1 is constituted by a variety of quantifiable features; we term these features sub-phenotypes . Our main focus is on sub-phenotypes with published evidence of variation in expression from an inherited component. These include our primary sub-phenotype of spinal neurofibroma burden (quantified by MRI of spinal neurofibromas) and the secondary sub-phenotypes of dermal neurofibroma burden, head circumference, number of Lisch nodules, scoliosis, history of plexiform neurofibromas, and height. Other sub-phenotypes, as collected by a routine history and physical, will also be evaluated. According to our hypothesis, the severity of a sub-phenotype will correlate with heritable differences in the germline expression of certain genes. As an example, consider a spectrum of individuals affected with the primary sub-phenotype of spinal neurofibroma burden. For most genes, there will be no relationship of expression level to the number of spinal neurofibromas. However, some genes will have a direct (or inverse, or other) correlation of their level of expression and the number of neurofibromas. Such genes would be considered as candidate modifier genes. The secondary sub-phenotypes will also be analyzed in a similar way. To limit false positives, candidate genes will then be tested for association (using the transmission/disequilibrium test, TDT) with the appropriate sub-phenotype. Recruitment will be focused on identifying individuals with a range of severity of the primary sub-phenotype, spinal neurofibroma burden. We will primarily recruit post-pubertal individuals who meet the 1988 NIH criteria for neurofibromatosis type 1 (NIH Consensus Development Conference 1988). We will exclude those with recognized segmental or mosaic NF1. The rate of cutaneous neurofibroma growth and number is known to vary widely; these tumors typically appear in adolescence. For this reason we will ascertain patients after puberty. We expect most individuals to be 18 years or older, but will also accept post-pubertal pediatric patients (and use a hand film to demonstrate bone age). Parents (whether affected or not) are critical when using family-based tests of association (like the TDT) and tests of linkage and will also be recruited. Tests of association with the TDT require trios (mother, father, proband). Multiple trios can be derived from a single family, if there are multiple affected individuals within the family. We set a recruitment goal of 100 trios and a ceiling of 1500 individuals (500 affected individuals, plus 1000 parents or additional sibs in about 400 families). In the interest of improving care for people living with NF1, this protocol also seeks to characterize, at the PI s discretion, individuals with unique or under-recognized features of NF1 as well as individuals with NF1-like phenotypes, including those patients with a known or suspected RAS pathway disorder.

Keywords

Eligibility

Minimum Age: 2 Years

Eligible Ages: CHILD, ADULT, OLDER_ADULT

Sex: ALL

Healthy Volunteers: No

Locations

Contact Details

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