INTRODUCTION
Neurofibromatosis type 1 (NF1), a common autosomal dominant Mendelian
disorder, has an unpredictable presentation with a wide spectrum of
inter- and intra-family clinical variability.1 With an
incidence of one in 3000,2 it is caused by
loss-of-function pathogenic variants of the NF1 tumor suppressor gene,
which is located on chromosome 17q11.2 and encodes neurofibromin, a
negative regulator of RAS proteins.3
For its diagnosis, at least two of the following criteria must be
satisfied: presence of >6 café-au-lait spots or
hyperpigmented macules (>5 mm and >15 mm in
diameter in prepubertal and postpubertal children, respectively);
>2 neurofibromas or one plexiform neurofibroma (pNF);
>2 inguinal and axillary freckles; optic nerve glioma; two
or more Lisch nodules; sphenoid dysplasia or typical long bone
abnormalities such as pseudarthrosis; and a first-degree relative with
NF1.3 Children with a severe phenotype have cutaneous
neurofibromas (cNF) or pNF, gliomas of the optic pathway, and peripheral
nerve sheath tumors.4
The complexity and diversity of pathogenic variants of NF1 gene make
genotype-phenotype correlations very difficult. Establishing this
association is potentially useful for targeted therapeutic intervention.