Last Updated: 06/1/19
Neurofibromatosis Type 1 (NF1), Neurofibromatosis Type 2 (NF2), and Schwannomatosis (SWN/NF3)
- Reason for Confusion
- NF2 Diagnosis Criteria
- NF1 Diagnosis Criteria
- Schwannomatosis (SWN/NF3) Diagnosis Criteria
- Confirmed (Definite) Diagnosis
- Presumed (Probable) Diagnosis
The three forms of neurofibromatosis are; neurofibromatosis 7ype 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis
It is important to understand that while NF is rare, it is statistically unlikely to have more than one form of NF. It is also statistically
likely for a person with any of the three types to be told they might have more than one type of NF. Since tumor growth for each is
different, it is important to know for a fact which type a person has. Due to similarities between the three forms, the accidental diagnosis
of more than one form of NF is an easy one for doctors to make.
1. Reason for Confusion
All three forms of NF can result in tumors that may be seen as bumps just below the surface of the skin, cutaneous and subcutaneous tumors.
In a person with NF1, these tumors are neurofibroma. In people with NF2 or Schwannomatosis, they would be schwannoma. It is
argued by some doctors, that it is possible for neurofibroma to also grow in individuals with NF2. The distinction between the Neurofibroma and
Schwannoma can only be determined by a biopsy but cannot with the use of an MRI alone. Some of these tumors are painful, some are not,
and there is typically a considerable amount more of skin surface tumors for people with NF1.
Skin discoloration spots of café-au-lait macules is also primarily an NF1 concern, but people with NF2 and SWN,
sometimes developing these, typically fewer than 6. These marks are not part of diagnosis criteria for NF2, or SWN.
2. Criteria for Neurofibromatosis Type 2 Diagnosis - the Baser Criteria
There have been different standards for diagnosis of NF2 since it was acknowledged as a condition different from NF1 and again when
Schwannomatosis was classified as a separate condition.
NF2 Diagnostic Criteria as of 2018 (December 2018 - now)
The 2018 revision of diagnosis for neurofibromatosis type 2 (NF2) change the tumor type of glioma, to ependymoma, and remove of
neurofibroma. [Evans, 2018]
||Added Features needed for Diagnosis
|Bilateral Vestibular Schwannoma
|First-degree relative with NF2
||Unilateral Vestibular Schwannoma, or
Any two (2) other NF2-Associated lesions:
Meningioma, Schwannoma, Ependymoma, or Juvenile Cataracts
|Unilateral Vestibular Schwannoma
||Any two (2) other NF2-Associated lesions:
Meningioma, Schwannoma, Ependymoma, or Juvenile Cataract
||Unilateral Vestibular Schwannoma, or
Any two (2) other NF2-Associated lesions:
Schwannoma, Ependymoma, or Juvenile Cataracts
3. Neurofibromatosis Type 1
NF1: Diagnostic Criteria
In 2003 it was determined that NF1 was caused by damage to Chromosome 17q11.2 and can be found there in genetic testing.
The NIH diagnostic criteria for NF1 in an individual who has two or more of the following features:
- Six or more Café-au-lait Macule Spots over 5mm in greatest diameter in prepubertal individuals
and over 15mm in greatest diameter in post pubertal individuals
- Two or more neurofibromas of any type or one Plexiform Neurofibroma
- Freckling in the Axillary or Inguinal Regions
- Optic Glioma
- Two or more either Lisch Nodules (Iris Hamartomas)
- A distinctive osseous lesion such as sphenoid Dysplasia, or Tibial Pseudarthrosis
- A first-degree relative (parent, sibling, or offspring) with NF1 as defined by the above criteria
The hallmark of neurofibromatosis type 1 (NF1) is the onset of dermal or plexiform neurofibromas.
4. Schwannomatosis (SWN/NF3) 
A percentage of individuals with NF2 were displaying symptoms differently. In 2005 the development of genetics found
out why when these individuals had a different genetic mutation. While some issues are in fact the same with individuals who have NF2,
Schwannomatosis ( SWN / NF3 ) is, in fact, its own condition.
Schwannomatosis is caused by a mutation in the SMARCB1 gene (SWI/SNF) or the LZTR1 gene.
SWN: Diagnostic Criteria
The diagnostic criteria for a person to be diagnosed with schwannomatosis, congenital neurilemmomatosis, follow a strict guideline established by the NIH.
A diagnosis for Schwannomatosis may be established if a person meets one of the conditions identified below.
Confirmed (Definite) Diagnosis of Schwannomatosis:
- Two (2) or more Non-Intradermal Schwannomas (at least one (1) with histological confirmation)
- No evidence of a vestibular tumor on high-quality MRI scan no known constitutional NF2 mutation
- One (1) pathologically confirmed Non-Vestibular Schwannoma plus a first-degree relative who meets the above criteria
Presumed (Probable) Diagnosis of Schwannomatosis:
- Two (2) or more non-intradermal schwannomas (at least one (1) with histological confirmation)
- No evidence of vestibular tumor on high quality MRI scan
- No known constitutional NF2 mutation
- No symptoms of 8th Cranial Nerve dysfunction
- Radiographic evidence (image scans) of a Non-Vestibular Schwannoma plus a first-degree relative meeting the criteria for
NF3: Genetic Criteria
In 2013, individuals showing signs of Schwannomatosis with no markers for the SMARCB1 protein were finally established to have an alteration
of the LZTR1 protein.
- Multiple Neurilemmomas
- Multiple Schwannomas
- Neurilemmomatosis, Congenital Cutaneous
- Neurofibromatosis Type 3
These can be dark brown, or light brown, contrast areas of different skin pigmentation, and may be about 1". Often such a mild difference in skin
tone they may be unnoticed or difficult to see in pictures. These can also fade over the years. No treatment is necessary.
If an individual in a family has Neurofibromatosis (NF); Neurofibromatosis Type 1 (NF1), Neurofibromatosis Type 2 (NF2), or Schwannomatosis (SWN/NF3)
also develop these marks, medical review of health for the same form of NF.
- NF1 more than 6 CALMS
- NF2 unlikely to develop 6 CALMS
- SWN unlikely to develop CALMS
The presence of Café-au-lait Macules (CALMs) should raise the suspicion of a genetic condition and physical examination for cause is important.
Also the result of:
- Ataxia Telangiectasia
- Basal Cell Nevus Syndrome
- Bloom Syndrome
- Chiak-Higashi Syndrome
- Fanconi Anemia
- Gaucher Disease
- Hunter Syndrome
- Legius Syndrome
- Maffucci Syndrome
- McCune-Albright Syndrome
- Multiple Mucosal Neuroma Syndrome
- Silver-Russell Syndrome
- Tuberous Sclerosis
- Watson Syndrome
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OMIM - Online Mendelian Inheritance in Man. "#101000 NEUROFIBROMATOSIS, TYPE II; NF2"
OMIM - Online Mendelian Inheritance in Man. "#162091 SCHWANNOMATOSIS 1; SWNTS1"
Celano, Emma, et al. "Spinal cord ependymoma: a review of the literature and case series of ten patients." Journal of neuro-oncology 128.3 (2016): 377-386.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705940/ | doi: 10.1007/s11060-016-2135-8
Genetic Home Reference "NF1 gene, neurofibromin 1"
OMIM - Online Mendelian Inheritance in Man. " * 613113 - NEUROFIBROMIN 1; NF1"