Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content +++ Key Points ++ Disease summary: Neurofibromatosis type 1 (NF1) is a common (∼1/3000), progressive neurocutaneous disorder primarily of increased tumor predisposition, but also pigmentary abnormalities, osseous dysplasia, and impaired cognitive function that arises secondary to mutations in the tumor suppressor gene NF1. NF1 is a pleiotropic disorder, affecting different organ systems (central and peripheral nervous systems, bone, vasculature) with wide variation in severity of clinical features, even among members of the same family. There is limited genotype-phenotype correlation (see Counseling). NF1 affects all ethnic groups and both sexes equally. As a population, individuals with NF1 have a reduced lifespan. Hereditary basis: NF1 is a monogenic disorder with an autosomal dominant pattern of inheritance. It is 100% penetrant, typically by late adolescence. Approximately half of the individuals affected with NF1 have a family history of the disorder. Differential diagnosis: The diagnosis is rarely mistaken in a patient with numerous café-au-lait macules, neurofibromas, and axillary freckling. Certain features, especially when present in isolation or in a younger patient, may present a diagnostic challenge (Table 108-1). Consideration of a missense NF1 mutation, or a de novo NF1 mutation present in a segmental or mosaic state (see Counseling) should be made when confronted with either café-au-lait macules only or neurofibromas only, especially in a limited distribution. A diagnosis of Legius syndrome should be considered in older individuals with pigmentary findings only and absence of neurofibromas. ++Table Graphic Jump LocationTable 108-1Differential Diagnosis of Isolated Disease Features in NF1View Table||Download (.pdf) Table 108-1 Differential Diagnosis of Isolated Disease Features in NF1 Syndrome Gene Symbol Associated Findings Pigmentary abnormalities, especially numerous café-au-lait macules Mosaic or segmental NF1 NF1 Mild (mosaic) or isolated (segmental) manifestations of classical NF1 Missense mutation in NF1 NF1 Varied; NF1 gene testing often helpful Legius/NF1-like syndrome SPRED1 Lipomas, macrocephaly, learning disabilities Neurofibromatosis type 2 NF2 Bilateral vestibular schwannomas, schwannomas elsewhere, lens opacities. Typically few café-au-lait macules Constitutional mismatch repair-deficiency syndrome (homozygosity or compound heterozygosity for mutations in listed genes) MLH1, MSH2, MSH6, PMS2 Hematologic malignancy and brain tumors in childhood; also early-onset GI malignancies Family history of HNPCC/Lynch syndrome Skin findings only in autosomal recessive form Bannayan-Riley-Ruvalcaba PTEN Pigmentation of glans and shaft of penis in boys; café-au-lait macules typically not widely distributed McCune-Albright syndrome with polyostotic fibrous dysplasia GNAS “Coast of Maine” or jagged appearance to café-au-lait macules; bony abnormalities LEOPARD syndrome PTPN11, RAF1, BRAF Multiple lentigines, pulmonic stenosis, growth retardation, sensorineural deafness; no tumors Ring chromosome phenotype Various chromosomes Short stature, microcephaly, moderate-to-severe mental retardation are also seen Neurofibromas Mosaic or segmental NF1 NF1 Mild (mosaic) or isolated (segmental) manifestations of classical NF1 Spinal neurofibromatosis NF1 Neurofibromas of spine but few dermal neurofibromas or pigmentary abnormalities, often do not meet consensus criteria for diagnosis of NF1 (see Diagnostic Criteria and Clinical Manifestations) Neurofibromatosis type 2 NF2 Bilateral vestibular schwannomas, schwannomas elsewhere, lens opacities. Typically few café-au-lait ... Your Access profile is currently affiliated with [InstitutionA] and is in the process of switching affiliations to [InstitutionB]. Please select how you would like to proceed. Keep the current affiliation with [InstitutionA] and continue with the Access profile sign in process Switch affiliation to [InstitutionB] and continue with the Access profile sign in process Get Free Access Through Your Institution Learn how to see if your library subscribes to McGraw Hill Medical products. Subscribe: Institutional or Individual Sign In Error: Incorrect UserName or Password Username Error: Please enter User Name Password Error: Please enter Password Sign in Forgot Password? Forgot Username? Sign in via OpenAthens Sign in via Shibboleth You already have access! Please proceed to your institution's subscription. Create a free profile for additional features.