Neurofibromatosis type 2 with multiple primary brain tumors in monozygotic twins

Abstract BACKGROUND Although monozygotic twins with neurofibromatosis complicated by brain tumors rarely have been reported, none of them fulfilled the diagnostic criteria for neurofibromatosis type 2 (NF2). METHOD We describe here the first pair of monozygotic twins with NF2, and the result of the molecular analysis of their NF2 gene. RESULTS One of the brothers (Case 1) developed tetraparesis and cerebellar truncal ataxia at age 12. He had no skin lesions. Radiological examinations revealed, at one time or another, bilateral vestibular schwannomas, a foramen magnum meningioma, five supratentorial meningiomas, and multiple spinal cord tumors. He underwent three operations over a 10-year period to remove tumors. The patient is now 23 years old and is in college. Although asymptomatic when examined at age 12, CT scan revealed that his brother (Case 2) also had multiple brain tumors, including meningiomas, schwannomas, and multiple spinal tumors. Tumors were removed in eight operations over a 10-year period. The patient is now deaf and confined to a wheelchair. An identical nonsense mutation caused by a C to T transition (C169) in a CpG dinucleotide of the NF2 gene was identified in both patients. CONCLUSION These results led us to speculate that dissimilarities with respect to time of appearance, distribution, and extent of symptoms and tumors between the twins were dependent on the influence of other genetic factors.