PracticeUpdate: Dermatology - Vol 1 - No.1 - 2017

PAEDIATRIC DERMATOLOGY 22

Predicting neurofibromatosis type 1 risk among children with isolated café-au-lait macules Journal of the American Academy of Dermatology Take-home message • The authors of this retrospective study developed an algorithm to predict the risk for neurofibromatosis type 1 (NF1) based on age, the number of café-au-lait macules (CALMs), and the presence of atypical CALMs (irregular margins and ragged borders) in children with isolated CALMs. Children older than 29 months with one or more atypical CALM but fewer than six CALMs had a 0.9% risk of NF1. In contrast, children younger than 29 months with six or more CALMs had an 80.4% risk of NF1. • The presence of more than six CALMs in a child younger than 2.5 years of age is associated with a high risk of NF1. An algorithm incorporating age, number of CALMs, and presence of atypical CALMs allows for an accurate NF1 risk assessment in children with isolated CALMs.

COMMENT By Shay Ben Shachar MD A lthough isolated café-au-lait mac- ules (CALMs) are a common skin finding, they are an early feature of neurofibromatosis type 1 (NF1) and usually serve as its presenting sign. In the absence of a positive family history, it is impossible to determine whether young children presenting with isolated CALMs have NF1 or not. Such determi- nation can be made only after a further follow-up or performance of a genetic analysis. We proposed a diagnostic algorithm to allow for the categorisation of individuals with isolated CALMs as being at low or high risk for having NF1. Individuals with isolated CALMs and an eventual diagnosis of NF1 (based on molecular analysis or clinical diag- nosis achieved later) presented at a younger age to the neurofibromatosis clinic or the diagnostic lab, had higher frequency of six or more CALMs, and a lower chance of having atypical CALMs at presentation, compared with those who did not have an eventual diagno- sis of NF1. According to the algorithm developed, children older than 29 months with isolated CALMs and at least one atypical CALM or fewer than six CALMs have about a 1% risk for con- stitutional NF1 while children under 29 months old with isolated CALMs have a high risk of about 80% for having NF1. This simple algorithm enables cat- egorisation of individuals with isolated CALMs as being at low or high risk for having NF1.

Abstract BACKGROUND Although isolated café-au-lait mac- ules (CALMs) are a common skin finding, they are an early feature of neurofibromatosis type 1 (NF1). OBJECTIVE We sought to develop an algorithm determining the risk of children with CALMs to have constitutional NF1. METHODS We conducted a retrospective study of patients with isolated CALMs. Diagnosis of NF1 was based on detecting NF1 mutation in blood or fulfilling clinical criteria. RESULTS In all, 170 of 419 (41%) and 21 of 86 (24%) children with isolated CALMs who underwent molecular testing and clinical follow-up, respec- tively, were given a diagnosis of NF1. Presence of fewer than 6 CALMs at presentation or atyp- ical CALMs was associated with not having NF1 (P < 0.001). An algorithm based on age, CALMs number, and presence of atypical macules

predicted NF1 in both cohorts. According to the algorithm, children older than 29 months with at least 1 atypical CALM or less than 6 CALMs have a 0.9% (95% confidence interval 0–2.6%) risk for constitutional NF1 whereas children younger than 29 months with 6 or more CALMs have a high risk (80.4%, 95% confidence interval 74.6–86.2%). LIMITATIONS The study was designed to detect constitutional NF1 and not NF1 in mosaic form. CONCLUSIONS A simple algorithm enables cat- egorization of children with isolated CALMs as being at low or high risk for having NF1. Predicting neurofibromatosis type 1 risk among children with isolated café-au-lait macules. J Am Acad Dermatol 2017 Mar 15;[EPub Ahead of Print], S Ben-Shachar, T Dubov, H Toledano-Al- hadef, et al.

Dr Shachar is a paediatrician practising in Houston, Texas.

PRACTICEUPDATE DERMATOLOGY