Monozygotic twins with Neurofibromatosis type 1, concordant phenotype and synchronous development of MPNST and metastasis.
BACKGROUND
Neurofibromatosis type 1 is a common autosomal dominant disorder with full penetrance and variable expression. The condition predisposes individuals to the development of malignant nervous system tumours, most frequently Malignant Peripheral Nerve Sheath Tumours (MPNSTs). Previous studies indicate that genetic factors other than mutations in NF1 may be responsible for the condition's variable expression.


METHODS
Here we present data from a pair of monozygotic twins affected by Neurofibromatosis type 1 resulting from a de novo mutation. Both twins developed a left sciatic plexiform neurofibroma that evolved into MPNST at a similar age and they also developed pulmonary metastasis at the same age. Other concordant traits between the twins were: macrocephaly, psychomotor delay, café-au-lait spots, cutaneous neurofibromas, retroperitoneal, pleural and paraspinal neurofibromas. The main discordant features observed were tibial pseudoarthrosis, pectus carinatum, osteoporosis and thymus hyperplasia.


CONCLUSIONS
This is the first report of monozygotic twins with Neurofibromatosis type 1 that develop MPNSTs, the localization and chronological evolution of which, and its metastasis, is concordant in both twins. These cases suggest that the events involved in the transformation of benign plexiform neurofibromas to MPNSTs in Neurofibromatosis type 1, follow a spatiotemporally programme that is influenced by heritable factors other than NF1 mutations.
Melean
German
G
Unidad de Genética Molecular, Hospital Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria and Centro de Investigación Biomédica en Red de Enfermedades Raras, Instituto de Salud Carlos III, Spain.
Hernández
Alba Marina
AM
Valero
María Carmen
MC
Hernández-Imaz
Elisabete
E
Martín
Yolanda
Y
Hernández-Chico
Concepción
C
D000328:Adult; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000150:complications / Q000175:diagnosis / Q000556:secondary*; D008297:Male; D009154:Mutation / Q000235:genetics; D018317:Nerve Sheath Neoplasms / Q000150:complications / Q000175:diagnosis / Q000473:pathology*; D009456:Neurofibromatosis 1 / Q000150:complications / Q000175:diagnosis / Q000473:pathology*; D025542:Neurofibromin 1 / Q000235:genetics; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011379:Prognosis; D014430:Twins, Monozygotic
D025542:Neurofibromin 1