International Journal of Dermatology | 2019
Segmental neurofibromatosis 1 with gonosomal mosaicism
Abstract
A man in his forties presented with multiple cutaneous nodules on his left flank that had been present for more than 20 years. Family history was notable for neurofibromatosis 1 (NF1) in his 21-year-old daughter who has caf e au lait macules (CALM) and axillary freckling. There are no other affected family members, including his wife and two other children. Physical examination revealed approximately 20 soft, flesh-colored papulonodules on the left flank (Fig. 1). There were no axillary or inguinal freckles, CALM, or Lisch nodules. The patient did not have any neurological deficits or symptoms. Previous biopsy of the patient’s papulonodules showed a diffuse proliferation of spindle cells and scattered mast cells within a fibrillary matrix consistent with neurofibroma (Fig. 2). Given the constellation of findings, he was diagnosed with segmental NF1 (SNF1), which is characterized by cutaneous features of NF1 (CALM and/or neurofibromas), limited to one body segment. He had no evidence of plexiform disease or systemic complications, and was scheduled for follow-up with dermatology and ophthalmology for surveillance. The occurrence of one daughter with classical NF1 and two unaffected children in this patient with SNF1 is consistent with gonosomal mosaicism. Genetic counseling was offered and deferred as the patient and his spouse have no future plans to conceive. NF1 is an autosomal dominant disorder resulting from germline mutations in neurofibromin, NF1. SNF1 is a rare form of NF1 that is regionally limited and can present with CALM and/or neurofibromas, or plexiform neurofibromas alone. The distribution is usually unilateral but can be bilateral. SNF1 is generally thought to occur due to postzygotic mutations in NF1, resulting in somatic mosaicism, without affecting the germline. By contrast, mutations arising during very early stages of embryonic development can cause mosaicism in both somatic cells and germ cells (gonosomal mosaicism). Gonosomal mosaicism, while rare, has been previously reported with SNF1 and is important to recognize as NF1 is among the most common tumor-prone autosomal dominant diseases. Moreover, though NF1 can arise from de novo sporadic mutations, almost half of the cases arise from inherited germline mutations. Therefore, clinicians should be aware in order to facilitate genetic counseling in individuals with SNF1 about the risk of NF1 in their offspring. Lastly, genetic counseling should extend to instances of eggor sperm-donor pregnancies, where gonosomal mosaicism in donor cells has been reported to result in offspring affected by classical NF1.