Utility of Genetic Testing of Various Tissues in Localized Mosaic Neurofibromatosis.

Background: Neurofibromatosis type 1 is one of the more common rare disorders, and its atypical/segmental or mosaic forms are underdiagnosed. Thus far, only a few dozen cases of localized mosaic neurofibromatosis have undergone combined germline and somatic genetic testing for the NF1 gene.

Methods: A 65-year-old female patient was referred to our center for multiple neurofibromas on her right shoulder, with a clinical diagnosis of localized mosaic neurofibromatosis. One of the neurofibromas was surgically removed. Massively parallel sequencing and multiplex ligation-dependent probe amplification were utilized to identify the germline and somatic variants in the NF1 gene.

Results: The heterozygous pathogenic NF1 gene variant c.7549C>T and multiple heterozygous intragenic NF1 gene deletions were detected in the DNA taken from the shoulder neurofibroma, but not in the DNA from blood leukocytes or buccal smear.

Study limitations: The healthy skin around neurofibromas was not analyzed due to limited available material.

Conclusion: Germline and somatic genetic testing in localized forms of neurofibromatosis are advisable since this facilitates proper genetic counseling regarding risks to offspring, who could inherit a germline pathogenic variant. Another important point to consider is cancer surveillance, which is often underutilized in mosaic forms of neurofibromatosis.