Predicting neurofibromatosis type 1 risk among children with isolated café-au-lait macules.
BACKGROUND
Although isolated cafe-au-lait macules (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, respectively, were given a diagnosis of NF1. Presence of fewer than 6 CALMs at presentation or atypical CALMs was associated with not having NF1 (P < .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%).


CONCLUSIONS
The study was designed to detect constitutional NF1 and not NF1 in mosaic form.


CONCLUSIONS
A simple algorithm enables categorization of children with isolated CALMs as being at low or high risk for having NF1.
Gilbert Israeli Neurofibromatosis Center, Tel-Aviv Medical Center, Tel-Aviv, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel. Electronic address: shayb@tlvmc.gov.il.
Shay
S
Ben-Shachar
Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Tom
T
Dubov
Gilbert Israeli Neurofibromatosis Center, Tel-Aviv Medical Center, Tel-Aviv, Israel; Pediatric Neurology Unit and Child Development Center, Tel-Aviv Medical Center, Tel-Aviv, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Hagit
H
Toledano-Alhadef
Pediatric Dermatology Unit, Tel-Aviv Medical Center, Tel-Aviv, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Jacob
J
Mashiah
Pediatric Dermatology Unit, Tel-Aviv Medical Center, Tel-Aviv, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Eli
E
Sprecher
Gilbert Israeli Neurofibromatosis Center, Tel-Aviv Medical Center, Tel-Aviv, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Shlomi
S
Constantini
Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Moshe
M
Leshno
Medical Genomics Laboratory, Department of Genetics, University of Alabama, Birmingham, Alabama.
Ludwine M
LM
Messiaen
D000465:Algorithms; D019080:Cafe-au-Lait Spots / Q000150:complications* / Q000235:genetics; D002675:Child, Preschool; D016514:Genes, Neurofibromatosis 1; D006801:Humans; D009154:Mutation; D009456:Neurofibromatosis 1 / Q000150:complications* / Q000453:epidemiology* / Q000235:genetics; D011379:Prognosis; D012189:Retrospective Studies; D018570:Risk Assessment
algorithm; café-au-lait macules; neurofibromatosis type 1; prediction