Differentials

Neurofibromatosis type 2 (NF2)

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

Bilateral vestibular schwannomas, intracranial meningiomas and/or ependymomas, spinal glioma, paraspinal schwannomas, cutaneous schwannomas, posterior subcapsular cataracts, pigmentary retinopathy, absence of typical café au lait spots.[26]

INVESTIGATIONS

Identification of a mutation at the NF2 locus in chromosome band 22q11.[27]

McCune-Albright syndrome

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

Very few or no café au lait spots, no axillary freckling, polyostotic fibrous dysplasia.[28]

INVESTIGATIONS

Identification of an activating mutation in the GNAS1 gene locus in chromosome band 20q13.2.

Familial café au lait spots

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

Absence of other features with NF1, even though the number of café au lait spots might suggest NF1.[9][29]

INVESTIGATIONS

Absence of an NF1 mutation.

NF1-like syndrome (Legius syndrome)

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

Absence of neurofibromas or optic pathway glioma or other features of NF1 except for the presence of café au lait spots, axillary freckling, macrocephaly, facial dysmorphism, and perhaps learning difficulties.[30]

INVESTIGATIONS

Identification of a mutation in the SPRED1 gene in chromosome band 15q13.2.[31]

Proteus syndrome

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

Localized overgrowth superficially mimicking ≥1 large diffuse plexiform neurofibromas in the absence of other features of NF1.[32][33]

INVESTIGATIONS

Absence of an NF1 mutation.

Age-related cutaneous neurofibromas

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

One to several cutaneous neurofibromas that do not buttonhole (i.e., push deeper into the dermis when pressed) and appear only in or beyond the fifth decade of life.[9]

INVESTIGATIONS

Absence of an NF1 mutation in a non-neurofibroma specimen.

Isolated diffuse plexiform neurofibroma

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

A diffuse plexiform neurofibroma in the absence of any other features of NF1.[9]

INVESTIGATIONS

Absence of an NF1 mutation in a non-neurofibroma specimen.

Schwannomatosis

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

Little or no skin pigmentation such as café au lait spots or intertriginous freckling. Multiple schwannomas.[34]

INVESTIGATIONS

Tumor biopsy uniformly "schwannoma". Absence of splicing or missense mutations.

Congenital mismatch repair deficiency

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

May have six or more café au lait spots, with typically more ragged edges.

INVESTIGATIONS

Homozygous mutations in one of the MMR genes: PMS2, MLH1, MSH6, MSH2.

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