Resources For Patients

Resources for Patients


Neurofibromatosis (NF) is a rare family of genetic syndromes with neurological and cutaneous manifestations, that typically results in the development of benign tumors of the nerves and growths in other parts of the body. This syndrome has a wide array of clinical presentations, with some people having barely any noticeable neurological problems, while others are severely impacted with significant impairment of quality of life. There are three major types: neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2) and schwannomatosis.

Neurofibromatosis type 1 (NF1)

NF1 is characterized by development of multiple light brown (café-au-lait) spots, freckling in the underarms and groin region, and multiple benign tumors (neurofibromas) along nerves and on the skins. Bone deformity and curvature of the spine (scoliosis) may also be present. Subset of patients will also develop tumors in the brain and along the spinal cord.

Diagnostic criteria
Clinical Diagnosis based on presence of two of the following:
1. Six or more café-au-lait macules over 5 mm in diameter in prepubertal individuals and over 15mm in greatest diameter in postpubertal individuals.
2. Two or more neurofibromas of any type or one plexiform neurofibroma.
3. Freckling in the axillary or inguinal regions.
4. Two or more Lisch nodules (iris hamartomas).
5. Optic glioma.
6. A distinctive osseous lesion such as sphenoid dysplasia or thinning of long bone cortex, with or without pseudarthrosis.
7. First-degree relative (parent, sibling, or offspring) with NF-1 by the above criteria.
*The diagnosis of NF1 requires at least two of the seven NIH criteria.

1 in every 3,000 people


Mutation of the NF1 gene on chromosome 17q, which produces a protein called neurofibromin. This gene is important in signalling pathways that help regulate cell growth, and disruption leads to uncontrolled growth of a cell.

Common Symptoms
  • Light brown spots on the skin called café au lait macules. These are benign and harmless
    spots in many people. These spots are usually present at birth or develop early in childhood.
  • Freckling in the underarms or groin area develop around 3-5 years of age. These lesions are also benign and tend to occur in skin folds.
  • Neurofibromas are benign tumors that develop underneath the skin or along larger nerves.
    Plexiform neurofibromas is a variant where a multilobulated tumor develops along a large
    portion of a nerve or multiple nerves. Plexiform neurofibromas have a 5-10% risk of malignant transformation into a cancerous sarcoma called malignant peripheral nerve sheath tumor (MPNST).
  • Bone deformities such as abnormal bone development or abnormal curved spine (scoliosis) is common. These can lead to bowing of the legs and factures that are difficult to heal.
  • Tumors of the optic nerve or tract in the central nervous system develops around 3 years of
    age, and rarely in late childhood. These tumors can sometimes impair vision.
  • Learning disabilities are common in children with NF1, often with problems with reading or mathematics. Attention-deficit/hyperactivity disorder (ADHD) and speech delays are also
  • NF1 children often are below average in height.
Neurofibromatosis type 2 (NF2)

NF2 is also characterized by development of benign tumors (schwannomas) within the nervous system tumors. The most common tumors are along the nerves that transmit sound and balance signals (cranial nerve VIII – vestibulocochlear nerve), and often develops on both the right and left side. Symptoms may manifest during childhood, adolescence, early adulthood or later in adult life. Some patients with NF2 will also develop clouding of the lenses of the eyes (cataracts), and other tumors along the lining of the brain and spinal cord.

Diagnostic criteria
Current and revised Manchester criteria for neurofibromatosis type 2 (NF2)
1. Bilateral vestibular schwannomas <70a or
2. FDR family history of NF2 and unilateral VS <70a or
3. FDR family history of NF2 or unilateral VS and 2 ofb meningioma, cataract, glioma, neurofibroma, schwannoma, cerebral calcification (if UVS + ≥2 nonintradermal schwannomas need negative LZTR1 testa ) or
Multiple meningiomas (2 or more) and 2 of unilateral VS, cataract, glioma, neurofibroma, schwannoma, cerebral calcification or
5. Constitutional or mosaic pathogenic NF2 gene mutation in blood or identical mutations in 2 distinct tumoursa
Abbreviations: FDR= first degree relative; UVS = unilateral vestibular schwannoma; VS = vestibular schwannoma.Ideally LZTR1 testing should be carried out on tutor tissue, but as mosaicism does dot appear as common in LZTR1 – affected individuals, blood will still give a useful result and probably exclude a germline schwannomatosis condition.
a2016 suggested revisions.
b Any 2 includes of any tutor type such as schwannoma.

1 in every 25,000 people


Mutation of the NF2 gene on chromosome 22q, which produces a protein called merlin (also known as schwannomin). This is a cytoskeleton protein that suppresses tumors, and disruption leads to uncontrolled growth of a cell.

Common Symptoms
  • Bilateral benign tumors called schwannomas on the hearing and balance nerves leads to gradual hearing loss, ringing in the ears and poor balance. Patients can also develop
    headaches and blockage of the cerebrospinal fluid pathway.
  • NF2 patients can also develop numbness, weakness, pain, and other neurological deficits due to compression of the brain, spine or peripheral nerves from benign tumors (schwannomas and meningiomas)
  • Impaired vision can develop secondary to cataract formation in early adulthood

Schwannomatosis is the least common form of neurofibromatosis, and as the name suggests predisposes patients to develop multiple benign tumors (schwannomas) along nerves in the body. The most common presenting symptom is diffuse pain that can occur anywhere in the body and may not be directly related to an underlying nerve tumor.

Diagnostic criteria
Combined molecular and clinical diagnoses
≥ 2 tutors with 22q LOH and 2 different somatic NF2 mutationsa+≥ 2 pathologically confirmed schwannomas or meningiomas
germline SMARCB1 or LZTR1 pathogenic mutation+one pathologically confirmed schwannoma or meningioma
Clinical diagnosis
≥ 2 non-intradermal schwannomas, one pathologically confirmed and no bilateral vestibular schwannoma by high-quality MRIb (some mosaic NF2 patients will be included in this diagnosis at a young age and some schwannomatosis patients may have unilateral vestibular schwannomas or multiple meningiomas)
one pathologically confirmed schwannoma or intracranial meningioma and an affected first degree relativec

1 in every 35,000 people


Two different genes have been implicated in the development of schwannomatosis (LZTR1 and SMARCB1), which are both tumor suppressors. This is a more complex condition, with a 3-step/4-hit hypothesis, where either LZTR1 or SMARCB1 is disrupted, as well as the NF2 gene for tumors to develop. In addition, LZTR1 and SMARCB1 mutations have only been observed in a subset of patients, which suggests that other genes might also be involved.

Common Symptoms
  • Chronic pain is a hallmark of schwannomatosis and can occur anywhere in the body. Pain
    can often be disabling.
  • Numbness, weakness, or other neurological deficits due to compression from benign tumors (schwannomas) along the brain, spine, or peripheral nerves.
Risk factors
  • Family history of neurofibromatosis is the biggest risk factor for development of these genetic conditions. Since NF1 and NF2 are autosomal dominant disorder, any parent who is affected by the condition has a 50% chance of having a child with the condition. The inheritance pattern of schwannomatosis is more complicated and unclear, with reported risk of inheriting the condition around 15%.
Local NF Clinics
Adult Neurofibromatosis Clinic

The Elisabeth Raab Neurofibromatosis clinic, the first in-Canada multidisciplinary clinic for adults with neurofibromatosis focuses solely on this genetic disorder. An estimated 10,000 Canadians are living with neurofibromatosis, a disorder that makes patients prone to develop innumerable tumors. This disease can be difficult to diagnose and manage, since all body systems can be involved, either directly or through neural or vascular influences.

The clinic offers a multidisciplinary team of neurologists, neurosurgeons, neuro-oncologists, medical geneticists, and genetic counsellors to provide a holistic approach to management of neurofibromatosis.

The clinic aims to advance treatment and understanding of neurofibromatosis in three key areas:

Clinical Care

On an outpatient basis, the clinic will assess, monitor and care for individuals from across Canada and North America living with neurofibromatosis, and speed up accurate diagnosis of those exhibiting symptoms related to this condition

Clinical Research

Clinical research focused on the patients visiting this specialized clinic helps provide a better understanding of neurofibromatosis, how many people are affected by it and how to improve existing treatments and develop new treatments for this condition

Basic Science

Scientific research in the laboratories in the Princess Margaret Cancer Research Centre and the Center for Research in Neurodegenerative Diseases will seek to better understand the genetic foundations of neurofibromatosis; how neural dysfunction occurs; and find possible ways to halt or reverse nerve damage

Toronto General Hospital 5Ec-309 200 Elizabeth Street Toronto, Ontario M5G 2C4

The Elisabeth Raab Neurofibromatosis Clinic at TGH is the first of its kind in Canada. (Photo: UHN)

How to Become a Patient?

Ask your family physician or general practitioner to send a formal referral to our clinic (details below).

Contact Information

Elisabeth Raab Neurofibromatosis Clinic
Calli Dreveny (Medical Administrative Assistant)
Phone: 416-340-4800 ext 3400
Fax: 416-340-4189
Address: Toronto General hospital, 200 Elizabeth Street, 5ECW-334

Pediatric Neurofibromatosis Clinics

The Pediatric Neurofibromatosis Clinic at SickKids Hospital. A dedicated pediatric neurofibromatosis clinic that offers comprehensive diagnostic evaluations, follow up care and genetic counselling for children, teens and young adults. The clinic provides compassionate care and access to broad range of subspecialties within SickKids Hospital. The program offers emotional support for your child and your family through access to psychosocial specialists and educational materials. In addition, the clinic offers unique clinical trials and treatment approaches through national research initiatives.

555 University Avenue, Toronto, Ontario, M5G 1X8

Contact Information

General Clinic Number for Appointments Phone: 416-813-5839
Dr Patricia Parkin Phone: 416-813-7654 ext 301544
Dr. Michael Weinstein Phone: 416-813-5281
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Café-au-lait Macules (CALM) Screening Clinic at SickKids Hospital

The aim of this clinic is to screen children with CALMs for prompt identification of patients with NF1 or other rare genetic disorders. This clinic run in conjunction with a dermatology,
geneticist, and genetic counsellors.


Black Wing, Main Floor, Clinic 7, 555 University Avenue, Toronto, Ontario, M5G 1X8

Contact Information

Phone: 416-813-7384
Fax: 416-813-7055
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Cutaneous Neurofibroma Laser Ablation Clinic

Cutaneous neurofibromas are histopathologically benign tumors that are the hallmark of neurofibromatosis type 1 (NF1). Although these tumors are not lethal, they are associated with significant impairment of quality-of-life due to cosmetic disfigurement. Previous studies have shown that visibility of cutaneous neurofibromas negatively impacted emotions and functioning. These findings underscore the need for effective therapy and prevention. As a result, cutaneous neurofibromas are the greatest medical burden in NF1 individuals.

We have developed a novel technique for treatment of cutaneous neurofibromas using an Yrbium-based laser for ablation of tumor. With this technology, we can treat several tumors within a short time period. The development of a periodical clinic dedicated to cutaneous neurofibromas will ensure that NF1 patients are seen in a timely manner to have their lesions treated in an outpatient setting.

Local NF Support Groups
Neurofibromatosis Society of Ontario

The Neurofibromatosis Society of Ontario (NFSO) provides services and support to families affected by NF1. The website contains educational information on NF1, personal stories, and community events.
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Tumor Foundation of BC

The Tumor Foundation of BC provides support, education, and research programs to improve the lives of patients and their families with neurofibromatosis.
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Neurofibromatosis Society of Nova Scotia

The Neurofibromatosis Society of Nova Scotia was set up to connect Nova Scotians with neurofibromatosis in hopes of providing the support that’s often in meeting people who can relate. The website provides information and pamphlets on neurofibromatosis to help educate patients and their families.
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L’Association de la Neurofibromatose du Quebec

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