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.