Risk factors, predictors of survival

[Guest guest]

A week ago someone posted to me that severity and course of disease is the

same for both probands and inherited, it is just that with inherited you are

looking for it and so pick it up before tumors get big. Actually, I think it

was Jon.

Well, here is one of those depressing predictor articles, which puts some

things differently.

Predictors of survival in neurofibromatosis 2. 1M.E. Baser, 2J.M. Friedman,

3D.G.R. . 1Los Angeles, U.S.A., 2Department of Medical Genetics,

University of British Columbia, Vancouver, Canada, 3Department of Medical

Genetics, St. 's Hospital, Manchester, U.K.

Neurofibromatosis 2 (NF2) is an autosomal dominant condition characterized

by benign nervous system tumors, ocular lesions, and cutaneous

abnormalities. In cross-sectional studies, germ-line NF2 mutation type is

associated with age at onset and with number of non-vestibular schwannoma

(VS) intracranial tumors. However, the natural history of the disease is

poorly characterized. We used the proportional hazards model to assess

molecular and clinical predictors of survival in the United Kingdom NF2

patient series (336 patients, 78 deceased, from 214 families). The patients

were aged 4 to 86 yrs (median, 34 yrs), were diagnosed from 1945-1998

(median, 1990), and were followed for a median of 9 yrs from onset of

symptoms. Of 144 patients from 77 families with identified germ-line NF2

mutations, 71 had frameshift or nonsense mutations, 27 had splice-site

mutations, 22 had missense mutations, 22 had large deletions, and 2 had

in-frame deletions. The clinical variables considered were presence of VSs,

non-VS cranial nerve tumors, spinal tumors, peripheral nerve tumors, lens

opacities, and various symptoms associated with CNS tumors; number of

intracranial meningiomas; ages at onset and at diagnosis; calendar year of

diagnosis; and proband status. Four clinical variables were independent

predictors of survival. The relative risk of death decreased 3.61-fold per

decade increase in age at diagnosis (p < .001) and 1.79-fold per decade

increase in calendar year of diagnosis (p < .001); increased 1.76-fold per

intracranial meningioma (p = .002); and was 2.23-fold higher in probands (p

= .007). There was a possible interaction between age at diagnosis and

number of meningiomas (p = .055). Germ-line NF2 mutation type did not

predict survival in these data. These results indicate that

readily-characterized clinical variables are associated with survival in

NF2.