Table IV.
Differential Diagnoses for NF1
| Condition and gene (if known) | Overlapping features | Distinguishing features |
|---|---|---|
| Neurofibromatosis type 2 (NF2) | CALS | Pathology of tumors is more often schwannoma, meningioma |
| Dermal and spinal cord tumors | Vestibular schwannomas (acoustic neuromas) leading to deafness in mid-adulthood | |
| Autosomal dominant | Juvenile posterior subcapsular cataract | |
| CALS do not meet NF1 diagnostic criteria | ||
| LEOPARD Syndrome (Lentigines, Electocardiographic abnormalities, Ocular Abnormalities, Pulmonic Stenosis, Abnormal Genitalia, Retardation of Growth and Deafness) (PTPN11) | CALS and hyperpigmented lesions | Deafness |
| Pulmonic stenosis | Multiple lentigines | |
| Autosomal dominant | ||
| McCune–Albright Syndrome (GNAS1) | CALS | Polyostotic fibrous dysplasia |
| Premature puberty | Endocrine abnormalities such as sexual precocity, hyperthyroidism, hyperparathyroidism | |
| CALS are atypical—fewer in number, larger in size and have irregular margins | ||
| Sporadic (only compatible with life when in the mosaic state) | ||
| Bannayan–Riley–Ruvalcaba Syndrome (PTEN) | CALS | Subcutaneous tumors are usually lipomas or hemangiomas |
| Multiple tumors | Polyposis of colon | |
| Macrocephaly | Pigmentary changes of penis in males | |
| Learning problems | ||
| Autosomal dominant | ||
| Multiple Lipomas | Subcutaneous tumors | Tumors are lipomas |
| Autosomal dominant | No other features of NF1 | |
| Proteus Syndrome (PTEN) | CALS | Epidermal nevi |
| Hemihypertrophy, | Tumors are lipomas, lymphangiomas, and hemangiomas | |
| Subcutaneous tumors | Bony abnormalities including: prominences of skull, macrodactyly and hyperostosis | |
| Overgrowth of limbs | Soft tissue hypertrophy may appear as gyriform especially over plantar surfaces of feet | |
| Learning disabilities | Sporadic | |
| Tuberous Sclerosis (TSC1; TSC2) | CALS | Additional dermatologic findings including: ash leaf spots, shagreen patches |
| Seizures | Pits in dental enamel | |
| Learning problems | Cardiac rhabdomyoma | |
| Behavior problems/ADHD | Angiomyolipomas of kidneys | |
| Autosomal dominant | Glioma/angiomas lesions in cortex and white matter (“tubers”) | |
| Familial Multiple CALS | CALS | No other features of NF1 |
| Autosomal dominant | ||
| Schwannomatosis | Multiple tumors | Schwannomas of cranial, spinal or peripheral nerves |
| No other features of NF1 | ||
| Mostly sporadic, though some reports of autosomal dominant inheritance | ||
| Multiple Endocrine Neoplasia, Type IIB (RET) | CALS | Tumors usually involve the endocrine system |
| Tumors including pheochromocytoma | Marfanoid habitus | |
| Autosomal dominant | ||
| Klippel–Trenauney–Weber (VG5Q) | Overgrowth | Port wine stains |
| Hemangiomas | ||
| Usually unilateral involvement | ||
| Sporadic | ||
| Homozygous mismatch repair gene mutations (PMS2, MLH1) | CALS | Family history consistent with Hereditary Nonpolyposis Colorectal Cancer |
| Tumors | Early onset HNPCC-related cancers | |
| Hematologic malignancies | Autosomal recessive, consanguinity common |