Is Neurofibromatosis Type 1-Noonan Syndrome a Phenotypic Result of Combined Genetic and Epigenetic Factors?

BACKGROUND/AIM Neurofibromatosis 1-Noonan syndrome (NFNS) presents combined characteristics of both autosomal dominant disorders: NF1 and Noonan syndrome (NS). The genes causing NF1 and NS are located on different chromosomes, making it uncertain whether NFNS is a separate entity as previously suggested, or rather a clinical variation. PATIENTS AND METHODS We present a four-membered Greek family. The father was diagnosed with familial NF1 and the mother with generalized epilepsy, being under hydantoin treatment since the age of 18 years. Their two male children exhibited NFNS characteristics. RESULTS The father and his sons shared R1947X mutation in the NF1 gene. The two children with NFNS phenotype presented with NF1 signs inherited from their father and fetal hydantoin syndrome-like phenotype due to exposure to that anticonvulsant during fetal development. CONCLUSION The NFNS phenotype may be the result of both a genetic factor (mutation in the NF1 gene) and an epigenetic/environmental factor (e.g. hydantoin).