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Misdiagnosis of "neurofibromatosis" in patients with piebaldism

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Letter: Misdiagnosis of “neurofibromatosis” in patients with piebaldism
Richard Spritz MD
Dermatology Online Journal 17 (11): 13

University of Colorado School of Medicine Aurora, Colorado


Miminal diagnostic criteria for the diagnosis of neurofibromatosis 1 (NF1) includes six or more café-au-lait macules plus axillary freckling. However, a recent report by Duarte et al claims co-occurrence of piebaldism and NF1 using this minimal criteria. We assert that this is not an accurate conclusion because both of these pigmentary findings occur frequently in typical cases of piebaldism.

In a recent publication in Dermatology Online Journal, Duarte et al [1] reported a family with purported co-occurrence of piebaldism and neurofibromatosis type 1 (NF1). It was claimed that these two autosomal dominant disorders co-segregated together at least from father to son. Clinical presentation of piebaldism was fairly typical, whereas the clinical diagnosis of NF1 was based solely on co-occurrence of axillary freckling and multiple café-au-lait macules; neither patient had any of the non-pigmentary features of NF1. Genetic testing demonstrated that both had a mutation of the KIT gene, p.Gly610Asp, but no mutation of the NF1 gene was documented.

Whereas there have been several previous reports of concomitant occurrence of piebaldism and NF1 [2, 3], we have previously pointed out [2, 3] that all of these appear to constitute misdiagnoses, based on inappropriate application of minimal clinical diagnostic criteria for NF1 [4, 5]. The observations of six or more café-au-lait spots together with axillary freckling are indeed considered sufficient to make the diagnosis of NF1 [3, 4] under the minimal diagnostic criteria for NF1 originally designed to facilitate clinical diagnosis in difficult cases. However, in patients with piebaldism, it is not appropriate to base a diagnosis of NF1 on the co-occurrence of café-au-lait spots and axillary freckling alone, because both of these are frequent clinical findings in piebaldism itself [2, 3].

It is certainly possible that piebaldism and NF1 could co-occur by coincidence and I am indeed aware of one such patient. However, in such cases the diagnosis of NF1 must be based on non-pigmentary diagnostic criteria for NF1, such as neurofibromata or demonstration of an NF1 gene mutation by DNA testing. The promulgation of this known diagnostic error by Duarte et al seems disingenuous because they apparently are aware of the problem, referencing the relevant publication in their discussion, but seem to dismiss the fundamental point as unimportant.


1. Duarte AF, Mota A, Baudrier T, Morais P, Santos A, Cerqueira R, Tavares P, Azevedo F. Piebaldism and neurofibromatosis type 1: family report. Derm Online J 2010;16(1):11. [PubMed]

2. Spritz RA. Genetic hypomelanoses: Disorders characterized by congenital white spotting — Piebaldism, Waardenburg syndrome, and related genetic disorders of melanocyte development — Clinical aspects. In, Nordlund JJ, Boissy RE, Hearing VJ, King RA, Oetting WS, Ortonne J-P, eds. The Pigmentary System. Blackwell, Malden, MA, 2nd Edn., 2006:pp.541-550.

3. Spritz RA, Itin PH, Gutmann DH. Piebaldism and neurofibromatosis type 1: Horses of very different colors. J Invest Dermatol 2004;122:xxxiv-xxxv. [PubMed]

4. National Institutes of Health Consensus Development Conference: Neurofibromatosis: Conference statement. Arch Neurol 1988;45:575-578. [PubMed]

5. Guttmann DH, Aylsworth A, Carey JC, Korf B, Marks J, Pyeritz RE, Rubenstein A, Viskochil D. The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2. JAMA 1997;278:5-57. [PubMed]

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