Clinicopathologic Assay of 15 Tumor Resections in a Family with Neurofibromatosis Type 2

Abstract

The objective of this study is the management of multiple family members with multiple neurofibromatosis type 2 (NF2) related tumors of the skull base that can be challenging, on purely technical, decision-making, and ethical levels. These issues are addressed in this manuscript based on an experience treating an unique large family with NF2. A retrospective chart review was performed, reviewing clinical, radiological, surgical, and pathological data. A unique family of 17 siblings, whose father was the proband as a sporadic mutation is reported. Over a 4-month period, five of eight affected siblings underwent 12 procedures for resection of 15 different NF2-related tumors. This single family experience of NF2-related skull base tumors underscores the importance of preservation of function and quality of life as the major determinants of treatment success.

Keywords

neurofibromatosis type 2 - NF2 associated tumors - vestibular schwannoma - meningioma - quality of life - ethics

• References

• 1 Baser ME ; Contributors to the International NF2 Mutation Database. The distribution of constitutional and somatic mutations in the neurofibromatosis 2 gene. Hum Mutat 2006; 27 (4) 297-306
• 2 Evans DG, Huson SM, Donnai D , et al. A genetic study of type 2 neurofibromatosis in the United Kingdom. I. Prevalence, mutation rate, fitness, and confirmation of maternal transmission effect on severity. J Med Genet 1992; 29 (12) 841-846
• 3 Parry DM, Eldridge R, Kaiser-Kupfer MI, Bouzas EA, Pikus A, Patronas N. Neurofibromatosis 2 (NF2): clinical characteristics of 63 affected individuals and clinical evidence for heterogeneity. Am J Med Genet 1994; 52 (4) 450-461
• 4 Trofatter JA, MacCollin MM, Rutter JL , et al. A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor. Cell 1993; 75 (4) 826
• 5 Rouleau GA, Merel P, Lutchman M , et al. Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2. Nature 1993; 363 (6429) 515-521
• 6 Mautner VF, Lindenau M, Baser ME , et al. The neuroimaging and clinical spectrum of neurofibromatosis 2. Neurosurgery 1996; 38 (5) 880-885, discussion 885–886
• 7 Evans DG, Huson SM, Donnai D , et al. A clinical study of type 2 neurofibromatosis. Q J Med 1992; 84 (304) 603-618
• 8 Evans DG, Birch JM, Ramsden RT. Paediatric presentation of type 2 neurofibromatosis. Arch Dis Child 1999; 81 (6) 496-499
• 9 Bennett RL, French KS, Resta RG, Doyle DL. Standardized human pedigree nomenclature: update and assessment of the recommendations of the National Society of Genetic Counselors. J Genet Couns 2008; 17 (5) 424-433
• 10 Evans DG, Watson C, King A, Wallace AJ, Baser ME. Multiple meningiomas: differential involvement of the NF2 gene in children and adults. J Med Genet 2005; 42 (1) 45-48
• 11 Evans GR, Lloyd SK, Ramsden RT. Neurofibromatosis type 2. Adv Otorhinolaryngol 2011; 70: 91-98
• 12 Evans DG, Trueman L, Wallace A, Collins S, Strachan T. Genotype/phenotype correlations in type 2 neurofibromatosis (NF2): evidence for more severe disease associated with truncating mutations. J Med Genet 1998; 35 (6) 450-455
• 13 Parry DM, MacCollin MM, Kaiser-Kupfer MI , et al. Germ-line mutations in the neurofibromatosis 2 gene: correlations with disease severity and retinal abnormalities. Am J Hum Genet 1996; 59 (3) 529-539
• 14 Baser ME, Kuramoto L, Woods R , et al. The location of constitutional neurofibromatosis 2 (NF2) splice site mutations is associated with the severity of NF2. J Med Genet 2005; 42 (7) 540-546
• 15 National Institutes of Health Consensus Development Conference. Neurofibromatosis. Conference statement. Arch Neurol 1988; 45 (5) 575-578
• 16 The Consensus Development Panel. National Institutes of Health Consensus Development Conference Statement on Acoustic Neuroma, December 11-13, 1991. Arch Neurol 1994; 51 (2) 201-207
• 17 Mautner VF, Tatagiba M, Guthoff R, Samii M, Pulst SM. Neurofibromatosis 2 in the pediatric age group. Neurosurgery 1993; 33 (1) 92-96
• 18 MacCollin M, Mautner VF. The diagnosis and management of neurofibromatosis 2 in childhood. Semin Pediatr Neurol 1998; 5 (4) 243-252
• 19 Nunes F, MacCollin M. Neurofibromatosis 2 in the pediatric population. J Child Neurol 2003; 18 (10) 718-724
• 20 Evans DG, Baser ME, O'Reilly B , et al. Management of the patient and family with neurofibromatosis 2: a consensus conference statement. Br J Neurosurg 2005; 19 (1) 5-12
• 21 Otsuka G, Saito K, Nagatani T, Yoshida J. Age at symptom onset and long-term survival in patients with neurofibromatosis Type 2. J Neurosurg 2003; 99 (3) 480-483
• 22 Baser ME, Friedman JM, Aeschliman D , et al. Predictors of the risk of mortality in neurofibromatosis 2. Am J Hum Genet 2002; 71 (4) 715-723
• 23 Crisci C. Tribute—and a clinical lesson in bioethics and quality of life. J Med Ethics 1997; 23 (1) 18
• 24 Brackmann DE, Fayad JN, Slattery III WH , et al. Early proactive management of vestibular schwannomas in neurofibromatosis type 2. Neurosurgery 2001; 49 (2) 274-280, discussion 280–283
• 25 Odat HA, Piccirillo E, Sequino G, Taibah A, Sanna M. Management strategy of vestibular schwannoma in neurofibromatosis type 2. Otol Neurotol 2011; 32 (7) 1163-1170
• 26 Samii M, Matthies C, Tatagiba M. Management of vestibular schwannomas (acoustic neuromas): auditory and facial nerve function after resection of 120 vestibular schwannomas in patients with neurofibromatosis 2. Neurosurgery 1997; 40 (4) 696-705, discussion 705–706
• 27 McCullough LB, Jones JW. Postoperative futility: a clinical algorithm for setting limits. Br J Surg 2001; 88 (9) 1153-1154
• 28 Moulton B, King JS. Aligning ethics with medical decision-making: the quest for informed patient choice. J Law Med Ethics 2010; 38 (1) 85-97
• 29 Natarajan SK, Sekhar LN, Schessel D, Morita A. Petroclival meningiomas: multimodality treatment and outcomes at long-term follow-up. Neurosurgery 2007; 60 (6) 965-979, discussion 979–981