See the spots

March 5, 2015

Clinical Vignette

During a sports physical you note a localized area of brown spots on the right side of the abdomen and right leg of a healthy 14-year-old girl. Her mother tells you that this has been present since birth. Although you clear her for sports activities, you consider the implications of the pigmented lesions. What’s the diagnosis?

Diagnosis and Clinical Presentation

The pigmented spots were typical of cafe au lait macules and together with the unilateral localized freckling in the groin crease (satisfying 2 NIH criteria for neurofibromatosis) were typical of segmental neurofibromatosis (SNF1). The neurofibromatoses are a group of hereditary diseases transmitted in an autosomal dominant fashion and are characterized by a tendency to form tumors of the ectodermal and mesodermal tissues(1). Obscurity and controversy still surround the topic of SNF1first described by Gammel in 1931. This variant of neurofibromatosis is a marker of somatic mosaicism resulting from a post-zygotic gene mutation. Although SNF1 has a reported prevalence of 0.002 % in the general population, the figure is probably higher, because subtle cases probably go undiagnosed (2). Manifestations of SNF1 most commonly include café au lait macules or neurofibromas or both in a single unilateral segment of the body. However, occasionally multiple segmental patches are present. Although lesions are usually unilateral, cases with bilateral, symmetrical or asymmetric involvement have been reported (2). Clinically, patients may be divided into four groups: those with only pigmentary changes or small cutaneous neurofibromas, those with both pigmentary changes and small cutaneous neurofibromas, and those with isolated plexiform neurofibromas (3). Some patients with SNF1 have had the complications similar to individuals with classic NF1, which include learning disabilities, optic pathway gliomas, and pseudoarthritis. Patients with learning difficulties tend to have more extensive cutaneous involvement(3). The progression of cutaneous lesions in SNF1 is similar to that of NF1. In both conditions plexiform neurofibromas and pigmentary lesions may be present at birth or childhood, whereas small cutaneous neurofibromas usually develop during preadolescence or adolescence. Although the risk of underlying complications is low, bony defects may occasionally be present at birth or develop during childhood. In most patients lesions are not symptomatic resulting in a delay in diagnosis (2).

Epidemiology and pathogenesis

Usually there is no family history of neurofibromatosis type 1 (NF1). However, even when lesions are localized gonadal mosaicism may rarely be present. Consequently, there may be a small risk of transmission of NF1 to children. Moreover, individuals with localized skin lesions may have mosaic involvement of other organ systems, so all patients require a careful skin examination, examination of family members, and search for extracutaneous findings. For instance, the presence of Lisch nodules should increase the concern for systemic involvement.

Our Patient

Our patient’s risk of developing serious sequelae is low. She is a high school honor student, and has no systemic symptoms of NF1. The risk of transmission to future children is her primary concern. Involvement of the skin overlying her right ovary raises the concern about involvement of her right ovary. At this time there are no reliable studies to confirm the diagnosis of SNF1 without systemic involvement or conditions associated with café au lait macules without NF1 or to exclude gonadal involvement if neurofibromatosis is present. Her primary care provider will follow the cutaneous lesions and he has a visit scheduled with genetics for further counseling in 2 years. The author would like to thank Airman Alexander Arrieta for assistance with the photos and to patient and her family for their cooperation in helping us bring this project to fruition.

Conclusion

Segmental cafe au lait macules and freckling should prompt consideration of segmental neurofibromatosis.

References

  1. Hirsch NP, Murphy A, Radcliffe JJ. Neurofibromatosis: Clinical Presentations and Anaesthetic Implications. British Journal of Anaesthesia 2001; 86: 555-64.
  2. Consoli C, Moss C, Green S, Balderson D, Cooper D, and Upadhyaya, M. GonosomalMosaicism for a Nonsense Mutation (R1947X) in the NF1 Gene in Segmental Neurofibromatosis Type 1. Journal of Investagational Dermatology 2005; 125: 463-66.
  3. Victor F. Segmental Neurofibromatosis.Dermatology Online Journal 2005; 11 (4): 20.