Spinal and cutaneous schwannomatosis is a variant form of type 2 neurofibromatosis: a clinical and molecular study.
OBJECTIVE
To delineate the clinical phenotype, molecular basis, and implications for screening in patients and families with multiple schwannomas not generally involving the cranium.


METHODS
As part of a United Kingdom clinical and genetic study of type 2 neurofibromatosis (NF2) patients and families with multiple schwannomas who do not fulfil diagnostic criteria for NF2 have been identified. The clinical phenotype was studied in the extended families and molecular analysis was carried out at the NF2 gene locus on chromosome 22.


RESULTS
Patterns of inheritance in five families with schwannomatosis are consistent with inheritance of an autosomal dominant gene. The consistency of phenotype, with relative sparing of the cranium, is constant in these families. However, families which initially seem to be indicative of schwannomatosis may develop into classic NF2 as shown by a sixth family. Many of the tumours found in these families were referred to as "neurofibroma" when they were clearly schwannomas. This difference in classification has major implications for the relative risk of each particular type of neurofibromatosis and neuropathological review may be important in some cases. Genetic linkage analysis in the two largest families is entirely consistent with primary involvement of the NF2 gene.


CONCLUSIONS
Variant forms of neurofibromatosis have presented a dilemma in classification and determination of recurrence risks in families. Previous reports have suggested that schwannomatosis is a sporadic non-hereditary condition. Patients with multiple schwannomas are likely to have a variant form of NF2 and up to a 50% risk of passing on a gene predisposing to multiple schwannoma.
Evans
D G
DG
Department of Medical Genetics, St Mary's Hospital, Manchester, UK.
Mason
S
S
Huson
S M
SM
Ponder
M
M
Harding
A E
AE
Strachan
T
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D003937:Diagnosis, Differential; D017809:Fatal Outcome; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D008126:Lod Score; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D009442:Neurilemmoma / Q000175:diagnosis* / Q000235:genetics / Q000517:prevention & control; D016518:Neurofibromatosis 2 / Q000175:diagnosis* / Q000235:genetics / Q000517:prevention & control; D010375:Pedigree; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000517:prevention & control; D013125:Spinal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000517:prevention & control
D005819:Genetic Markers