Utility of Genetic Testing of Various Tissues in Localized Mosaic Neurofibromatosis

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.

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.

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.

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

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.