DISCUSSION
NF1 has a variable presentation that is dependent on age, making it
difficult to establish genotype-phenotype
correlations.5 Although there have been significant
developments in the research on NF1 underlying this phenotypic
heterogeneity are unknown. Only a small number of genetic abnormalities
have been correlated with a characteristic
phenotype.6,7
A large number of different mutations have been reported, but
submicroscopic deletions, splicing mutations, and stop mutations are the
most common. Submicroscopic deletions are responsible for 5–10% of
reported cases of NF1 and phenotypic variability is seen in these
patients because of differences in the size of the
deletion.6,7 Chromosome 17 submicroscopic deletions
are associated with a more severe phenotype, as seen in this patient.
This phenotype includes a high number of cNF and pNF at neonatal age,
dysmorphic facial features, intellectual disability, Lisch nodules, and
multiple brain hamartomas. However, our patient did not present with
other characteristic symptoms, such as somatic overgrowth, skeletal
abnormalities, connective tissue disorders, and cardiovascular
malformations, which are associated with submicroscopic deletions.
Although many different mutations associated with neurofibromatosis have
been reported, information on genotype-phenotype correlations remains
limited.8,9 The extreme variability in the clinical
presentation of NF1 makes these correlations difficult, although they
are crucial for the patient and his family.
The presence of a more severe phenotype warrants the search for
submicroscopic deletions and a precise monitoring of complications.