Nevus Anemicus as Indication of Neurofibromatosis Type 1 in Childhood

Aims: Neurofibromatosis type 1 (NF1) is a frequent genetic disease caused by NF1 mutations at 17q11.2. NF1 is mainly diagnosed based on clinical findings as NF1 mutational analysis is time consuming and does not offer a 100% detection rate. Clinical diagnosis is possible in the majority of affected children until the age of 6 years. However, at the age of 1 year or less, a definite diagnosis is impossible in 30% of patients. Therefore, it is important to define additional clinical findings that facilitate clinical diagnosis. We observed that nevi anemic (NA) occur with increased frequency in NF1 patients. These congenital cutaneous anomalies are characterized by palor and sharp margins and do not require therapy. Melanocyte function and skin sensitivity are normal. This study will establish the frequency of NA in children with possible NF1 to characterize NA as additional diagnostic criterion.

Methods: Our NF clinic cares for more than 600 patients at the age of 0 to 23 years. During a 3 months' period, we examined 51 patients. Age and sex were documented, and presence, location, and characteristic features of NA were described.

Results: NA were found in 16 (31%) patients examined (34 males, 17 females; age: 8 months–23 years). They were mainly located on the trunk, less frequently on the limbs.

Conclusion: NA are present in 1 to 2% of the general population and in up to 50% of NF1 patients. In our study, NA were found in 31% of NF1 patients. This is below the published frequency but still well above the general prevalence of NA. It is not known why NA appear with increased frequency in NF1. It has been postulated that NA are caused by increased α-adrenergic vasoconstriction. In addition, loss of β-adrenergic receptors has been shown in cultured NF1 fibroblasts. This imbalance between α- and β-adrenergic receptors in neurofibromin-deficient tissues might explain why NA frequently occur in NF1 patients.

On the basis of the published studies and our own observations, we propose that NA in children with suspected NF1 might facilitate definite diagnosis and improve clinical management.

Keywords: nevus anemicus, neurofibromatosis type 1, diagnostic criteria.