22 / 28
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.
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.
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.
Dr Shachar is a paediatrician
practising in Houston, Texas.
PAEDIATRIC DERMATOLOGY
22
PRACTICEUPDATE DERMATOLOGY