what is nf?

COMMON + RARE

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neurofibromatosis

Neurofibromatosis (NF) is a progressive disorder that causes tumors to grow on nerves throughout the body. It affects one in every 3,000 people and can lead to blindness, bone abnormalities, cancer, deafness, disfigurement, learning disabilities, and excruciating and disabling pain. Anyone can be born with NF, regardless of gender or race. It is under-recognized and underdiagnosed yet affects more people than cystic fibrosis, Duchenne muscular dystrophy, and Huntington’s disease combined.

A Brief History of Neurofibromatosis EARLY 1800’S First clinical description of NF2

1700’s

1800’s LATE 1700’S First clinical description of NF1

LATE 1800’S Characterization of NF1; original use of the term neurofibroma

1970’s

1987 Genetic markers for NF1 and NF2 are identified on chromosomes 17 and 22, respectively

1996 Drosophila melanogaster model of NF2 is developed

1997–2000 Strains of NF2 mutant mice are generated

1990 ’s

1980’s 1978 National Neurofibromatosis Foundation is established; now known as the Children’s Tumor Foundation

1993 Identification of the NF2 gene and description of its encoded protein, named merlin or schwannomin

1990 Identification of the NF1 gene and description of its encoded protein, named neurofibromin in 1992

1994 Strains of NF1 mutant mice are generated

2000– 1997 Drosophila melanogaster model of NF1 is developed

2003 Schwannomatosis is recognized as genetically distinct from NF2

SOURCE McClatchey AI. 2007 Annu. Rev. Pathol. Mech. Dis. 2:191-216

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THE THREE TYPES OF NF

Neurofibromatosis 1 (NF1)

NF1 occurs in one in 3,000 births and is characterized by multiple café au lait spots and neurofibromas (tumors) on or under the skin. Enlargement and deformation of bones and curvature of the spine (scoliosis) may also occur. Tumors may develop in the brain, on cranial nerves, or on the spinal cord. About 50% of people with NF1 also have learning disabilities.

Neurofibromatosis 2 (NF2)

NF2 occurs in one in 25,000 births and is characterized by multiple tumors on the cranial and spinal nerves, and by other lesions of the brain and spinal cord. Tumors that affect both of the auditory nerves are the hallmark of NF2 and hearing loss generally begins in the teens or early twenties.

Schwannomatosis

This rare form of NF has only recently been recognized and appears to affect around one in 40,000 individuals. It is less understood than NF1 and NF2, and its features may vary greatly between patients. Schwannomatosis can cause severe, chronic, and debilitating pain.

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SIGNS OF NF Only a trained physician can diagnose NF. The tentative diagnostic criteria for NF is two or more of the following symptoms, provided that no other disease accounts for the findings.

NF research also has the potential to benefit an additional 65 million people who have cancer and 35 million with learning disabilities.

pigmented bumps on the iris

tumor on the optic nerve that may interfere with vision

café au lait spots large swollen areas of the skin pea-sized bumps on the skin (neurofibromas) freckling under the arms or groin area

skeletal abnormalities such as bowing of the legs or thinning of the shin bone

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A VARIABLE DISORDER

There is no way to predict who will have a mild case of NF and who will develop serious complications. NF1

ctf.org/nf1

NF1 can result in disfiguring tumors, scoliosis, failing vision due to tumors that grow on the optic nerve, bone defects, high blood pressure, learning disabilities, and a large head size.

NF2

ctf.org/nf2

NF2 can result in hearing loss, ringing in the ears (called tinnitus), problems with balance, and tumors (called “schwannomas”).

Schwannomatosis ctf.org/schwannomatosis

People with schwannomatosis develop multiple tumors called schwannomas on cranial, spinal, and peripheral nerves, which can cause varying degrees of chronic pain.

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TREATING NF

There is no cure for NF.

Currently, therapy for patients with neurofibromatosis is a program of treatment by a team of specialists to manage symptoms or complications. At this time, surgery is frequently the only option. Patients often endure multiple surgeries throughout their lives to remove tumors. Although the majority of NF tumors are benign, a small percentage become cancerous. Chemotherapy is another treatment option in both cases.

Pictured is an x-ray showing several plexiform neurofibroma tumors along the spine and arm of a person with NF1

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LIVING WITH

NF NF affects more than two million people worldwide. This makes NF more prevalent than cystic fibrosis, Duchenne muscular dystrophy, and Huntington’s disease combined.

Clara is born in Kansas City, Missouri. Her Mom has NF1.

Clara is diagnosed with NF1 at 9 months, after her Mom sees several café au lait spots.

NF varies greatly between people who have the disorder. This story summarizes a possible set of experiences for someone who lives with NF.

Clara marries Dave, who she meets at an NF Endurance event.

Clara becomes a middle school history teacher.

Clara graduates from college with a degree in teaching.

Five years ago there were only two NF clinical trials in progress. Today, thanks to the Children’s Tumor Foundation, there is a pipeline of 25 trials ongoing, and more than 50 drugs in preclinical testing.

Clara and Dave meet with their doctor to discuss having a family.

NF can be inherited from a parent who has the disorder or may be the result of a new or spontaneous gene mutation.

Clara attends NF Walk, an event sponsored by Children’s Tumor Foundation.

Clara gets yearly checkups with her doctors who monitor her neurofibromas.

NFWALK

Clara takes extra classes in elementary and middle school for some of her learning disabilities.

Clara goes to NF Camp in Emigration Canyon, Utah.

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NF1 has a connection to developmental problems, especially learning disabilities, which are five times more common for people who have NF1.

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THE CHILDREN’S TUMOR FOUNDATION

The Children’s Tumor Foundation (CTF) is the first and largest NF organization in the world. As a non-profit 501(c)(3), the Foundation is dedicated to ending neurofibromatosis through research. Their work and support gives hope to millions of people who have the disorder, their families, and their caretakers by:

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Encouraging and supporting research and the development of treatments for neurofibromatosis types 1 and 2, schwannomatosis, and related disorders.

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Supporting people with NF, their families and caregivers by providing thorough, accurate, current and readily accessible information.

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Assisting in the development of clinical centers, best practices, and other patient support mechanisms (not including direct medical care) to create better access to quality healthcare for affected individuals.

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Expanding public awareness of NF to promote earlier and accurate diagnoses by the medical community, increasing the non-affected population’s understanding of the challenges facing persons with NF, and encouraging financial and other forms of support from public and private sources.

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CTF’S IMPACT ON NF RESEARCH “My daughter has NF1 and this is a disorder that not only affects her directly but our entire family. She is 6 years old and has already had two rounds of chemotherapy with very little effect, and they continue to find new tumors for which there are no proven treatments or cure. Please continue to help fund research so that my daughter can look to her future with hope.”

The Children’s Tumor Foundation funds several different NF research programs. In 2006 the Children’s Tumor Foundation established the Drug Discovery Initiative (DDI) Awards program to identify future candidates for clinical trials and drug development by testing them either in cell or animal models of NF. DDI Awards are intended to support initial proof of concept as to whether a drug has any potential as a candidate NF drug therapy. CTF has funded 26 DDI awards to test drugs for various NF1, NF2, and schwannomatosis tumors, bone dysplasia, and learning disabilities. Most of these awards show promise as catalysts that get new ideas off the ground. The DDI program funds the most promising ideas, even those that are challenging. Another Foundation initiative is the Neurofibromatosis Preclinical Consortium, (NFPC). This seven-year, $8 million dollar effort unites six major U.S. research centers, each focused on a different NF1 or NF2 tumor mouse model. Together these sites test promising preclinical drug candidates in multiple tumor models, to ensure that drugs are fully evaluated for potential clinical use in all NF tumor types. In order to efficiently translate biological findings into clinical benefit for NF patients, significant commitments from pharmaceutical companies, biotechs, and research and development initiatives are essential.

Dr. Scott Plotkin of Massachusetts General Hospital at the Children’s Tumor Foundation’s annual NF Conference.

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MATT HAY

Hay has had two brain surgeries, a spinal surgery, and five eye surgeries in the last decade. He has had to relearn to walk twice and learn to hear again once. “But I am quick to remind people that my case of NF2 can be considered mild in comparison to what others with this disorder deal with every day,” he says. The spine surgery left Matt with reduced nerve function in his arms and shoulders and problems with balance, so his arms tire easily when swimming, and he rode a 35-pound recumbent trike in the triathlon. Moreover, his eye doesn’t squint or tear due to a loss of facial nerve function, so when running he

IRONMAN + NF HERO

In September 2011, Matt Hay completed an Ironman-distance Rev3 triathlon in Sandusky, OH. Matt finished a 2.4 mile swim, a 112 mile bike ride, and a 26.2 mile run in 15:41:02, an incredible achievement. In addition to the Rev3 triathlon, Matt has completed an Olympic distance triathlon and a half Ironman triathlon in the last few years. These are tremendous endeavors by any measure, but Hay’s accomplishments are all the more remarkable because he lives with NF. Matt was diagnosed with NF2 in 1998. Over the next several years he gradually lost his hearing. In 2004, when deafness set in, Matt had an Auditory Brainstem Implant (ABI) surgically inserted. The ABI allows him to hear voices, but they sound robotic. He says it is most helpful during the biking portion of triathlons so that he can hear the bike gears click.

NF2 can cause hearing problems and even deafness when tumors grow on the vestibular nerve.

stops to use saline drops every mile or so to prevent eye damage.  Matt and his wife Nora are active fundraisers for the Children’s Tumor Foundation through the NF Endurance Team. They have run numerous marathons and half marathons and their efforts have raised more than $25,000. The Hay family has 5-year-old twins and a two-year-old, and they are Matt’s main inspiration. “I want them to think of their dad as the guy that did the Ironman rather than the guy that can’t smile all the way or hear very well.”

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HOW YOU CAN HELP

JOIN THE FIGHT TO END NF Make a Donation

Your donation directly supports neurofibromatosis research and helps ensure that the most promising projects are thoroughly funded and explored.

NF Walk Program

The NF Walk Program is a national fundraising program of the Children’s Tumor Foundation that supports NF research, raises awareness, and provides support for individuals with NF and their families. Every Step Makes A Difference.

NF Endurance Team

NF Endurance offers the opportunity for individuals to participate in marathons, triathlons, bike races, and other high endurance sporting events to raise money for research, promote awareness, and provide a network of caring support for those living with NF and their families. NF Endurance: Infinite Possibilities.

Racing4Research

A powerful fundraising initiative built around the Rolex 24 Hours At Daytona, R4R gives volunteers an opportunity to attend the most popular auto endurance race in the country while raising funds in the fight against NF. Help Fuel The Cure.

Join your Local Chapter

The Foundation has a presence in nearly all 50 states and facilitates patient support groups, medical symposia, and fundraising events. Learn more about the chapter in your area: ctf.org/chapters “My 7 year old son was diagnosed with neurofibromatosis type 1 at the age of 2. He has had numerous tests, scans, and needles every year since then. In order to find a cure for this disease, it must be better understood, therefore more research is necessary.”

www.ctf.org

For more information on these and other Children’s Tumor Foundation programs, please visit www.ctf.org

NFWALK

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About This Book

This book is the result of a partnership between Andrew Shea and the Children’s Tumor Foundation and is part of a nationwide NF awareness campaign. Sappi Fine Paper generously funded this project with one of their Ideas That Matter grants. Sappi also donated the paper that was used to make this book. This book was designed by Andrew Shea and Christina Beard, using two typefaces: Franchise and Open Sans. Some illustrations on page 10 came from the thenounproject.com.

www.sappi.com

Children’s Tumor Foundation 95 Pine Street, 16th Floor
 New York, NY 10005-1703

www.ctf.org [email protected] 1-800-323-7938

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