NF1 microduplication first clinical report: association with mild mental retardation, early onset of baldness and dental enamel hypoplasia?

NF1 microdeletion syndrome is a common dominant genomic disorder responsible for around 5% of type I neurofibromatosis cases. The majority of cases are caused by mutations arising within the NF1 gene. NF1 microdeletion carriers present a more severe phenotype than patients with intragenic mutations, including mental retardation, cardiac anomalies and dysmorphic features. Here, we report on two brothers with mental retardation presenting a microduplication of the NF1 microdeletion syndrome region detected by array-CGH analysis. Main phenotypic features are mental deficiency, early onset of baldness (15 years old), dental enamel hypoplasia and minor facial dysmorphism. The breakpoint regions coincide with the repeats, and the recombination hot spots shown to mediate NF1 microdeletion through NAHR. A screening of the patients' familial relatives showed that this microduplication segregates in the family for at least two generations. This result demonstrates that both deletion and duplication of the NF1 region, at cytogenetic band 17q11.2, give rise to viable gametes, even if only NF1 microdeletions have been reported until now. Our study reports seven cases of NF1 microduplication within one family. Similar phenotypic abnormalities were present in most of the individuals, however, two displayed a normal phenotype, suggesting a potential incomplete penetrance of the phenotype associated with NF1 microduplication.