NF1: Differential Diagnosis

Other syndromes that involve café-au-lait spots or similar pigmentary findings include ([Viskochil: 2010];[Jones: 1997]):
  • Legius syndrome – café au lait macules, learning disabilities (mutations in SPRED1)
  • Noonan syndrome – webbing of the neck, pectus abnormality, cryptorchidism, pulmonic stenosis;
  • McCune-Albright syndrome – polyostotic fibrous dysplasia, irregular skin pigmentation, sexual precocity;
  • Watson syndrome – café au lait macules, pulmonic stenosis, and low normal intelligence;
  • LEOPARD syndrome – multiple lentigines, ocular hypertelorism, pulmonic stenosis, abnormalities of the genitalia, growth retardation, deafness, pectus deformity;
  • Silver-Russel syndrome – short stature of prenatal onset, skeletal asymmetry, small incurved fifth finger;
  • Bloom syndrome – short stature, malar hypoplasia, telangiectatic erythema of the face;
  • Sotos syndrome – large size, large hands and feet, hypotonia;
  • Dubowitz syndrome – unusual facies, infantile eczema, small stature, mild microcephaly;
  • Klippel-Trenaunay-Weber syndrome – asymmetric limb hypertrophy, cutaneous vascular malformations; and
  • Proteus syndrome – hemihypertrophy, subcutaneous tumors, macrodactyly.
Neurofibromas in NF1 can be confused with other tumor syndromes including ([Viskochil: 2010];[Jones: 1997]):
  • Bannayan-Riley-Ruvalcaba syndrome – macrocephaly, polyposis of colon, lipomas, pigmentary changes of the penis;
  • Carney syndrome – nevi, atrial myxoma, neurofibromas, endocrine overactivity;
  • Proteus syndrome – hemihypertrophy, subcutaneous tumors, macrodactyly;
  • Maffuci syndrome – enchondromatosis, hemangiomata;
  • Multiple endocrine neoplasia 2B – multiple neuromata of tongue, lips with or without medullary thyroid carcinoma, with or without pheochromocytoma;
  • von Hippel-Lindau syndrome – retinal angiomata, cerebellar hemangioblastoma;
  • Gardner syndrome – intestinal polyposis; and
  • Schwannomatosis.
Neurofibromas typically appear after the development of the café au lait macules, beginning in late childhood and adolescence, and the presence of other NF1 findings aids in their diagnosis as benign hamartomas.

Authors & Reviewers

Current Authors and Reviewers:
Author: David A. Stevenson, MD
Reviewers: Karin Dent, MS, CGC
David Viskochil, MD, Ph.D.

Page Bibliography

Jones KL.
Smith's Recognizable Patterns of Human Malformation.
5th ed. Philadelphia: W. B. Saunders Company; 1997. 0721661157
Concise reviews of syndromes with an emphasis on dysmorphology. Syndromes described in sections broken down into abnormalities, natural history, and etiology.

Viskochil DH.
Neurofibromatosis Type 1.
Management of Genetic Syndromes, 3rd Edition. 2010; 549-568. New York: Wiley-Blackwell;
Excellent review of NF1 by an expert in the field. Book is a great resource for Medical Home providers, with chapters on 25 different genetic conditions.