PHENOTYPIC VARIABILITY IN MONOZYGOTIC TWINS WITH NEUROFIBROMATOSIS-2

Mutations in the neurofibromatosis 2 (NF2) tumor suppressor gene on ch romosome 22q12 cause a clinically variable autosomal dominant syndrome characterized by bilateral vestibular schwannomas (VSs), other nervou s system tumors, and early onset lenticular cataracts, We studied thre e pairs of monozygotic (MZ) twins with NF2, all with bilateral VSs, to separate genetic from nongenetic causes of clinical variability, The evaluation included gadolinium-enhanced high-resolution magnetic reson ance imaging of the head and spine, neuro-ophthalmic examination with slit lamp, physical examination, and zygosity testing with microsatell ite markers, Each MZ pair was concordant for general phenotypic subtyp e (mild or severe) and often for the affected organ systems, However, the MZ pairs were discordant for some features of disease presentation or progression, For example, all three pairs were discordant for pres ence or type of associated cranial tumors, We hypothesize that phenoty pic differences between NF2 MZ twins are at least partly due to stocha stic processes, such as the loss of the second NF2 allele or alleles o f other genes. (C) 1996 Wiley-Liss, Inc.