Neurofibromatosis type 1, inherited in an autosomal dominant pattern, is characterized by multiple café-au-lait macules (CALMs), skinfold freckling (more correctly termed lentiginous macules since they occur in non–sun exposed areas), iris Lisch nodules, tumors of the nervous system, and other features.
Revised diagnostic criteria for neurofibromatosis type 1 (NF1)
A) The diagnostic criteria for NF1 are met in an individual who does not have a parent diagnosed with NF1 if two or more of the following are present:
- Six or more café-au-lait macules over 5 mm in greatest diameter in prepubertal individuals and over 15 mm in greatest diameter in postpubertal individualsa
- Freckling in the axillary or inguinal regiona
- Two or more neurofibromas of any type or one plexiform neurofibroma
- Optic pathway glioma
- Two or more iris Lisch nodules identified by slit lamp examination or two or more choroidal abnormalities (CAs) – defined as bright, patchy nodules imaged by optical coherence tomography (OCT)/near-infrared reflectance (NIR) imaging
- A distinctive osseous lesion such as sphenoid dysplasia,b anterolateral bowing of the tibia, or pseudarthrosis of a long bone
- A heterozygous pathogenic NF1 variant with a variant allele fraction of 50% in apparently normal tissue such as white blood cells
B) A child of a parent who meets the diagnostic criteria specified in A merits a diagnosis of NF1 if one or more of the criteria in A are present
a If only café-au-lait macules and freckling are present, the diagnosis is most likely NF1 but exceptionally the person might have another diagnosis such as Legius syndrome. At least one of the two pigmentary findings (café-au-lait macules or freckling) should be bilateral.
b Sphenoid wing dysplasia is not a separate criterion in case of an ipsilateral orbital plexiform neurofibroma
- Legius E, Messiaen L, Wolkenstein P, Pancza P, Avery RA, Berman Y, Blakeley J, Babovic-Vuksanovic D, Cunha KS, Ferner R, Fisher MJ, Friedman JM, Gutmann DH, Kehrer-Sawatzki H, Korf BR, Mautner VF, Peltonen S, Rauen KA, Riccardi V, Schorry E, Stemmer-Rachamimov A, Stevenson DA, Tadini G, Ullrich NJ, Viskochil D, Wimmer K, Yohay K; International Consensus Group on Neurofibromatosis Diagnostic Criteria (I-NF-DC), Huson SM, Evans DG, Plotkin SR. Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation. Genet Med. 2021 May 19. [Medline]
- Corsello G, Antona V, Serra G, Zara F, Giambrone C, Lagalla L, Piccione M, Piro E. Clinical and molecular characterization of 112 single-center patients with Neurofibromatosis type 1. Ital J Pediatr. 2018 Apr 4;44(1):45. [Medline]
Created Jun 01, 2021.