A de novo em ~1.3 Mb microdeletion at 17q11.2 associated with Neurofibromatosis-Noonan syndrome

Introduction: Neurofibromatosis-Noonan syndrome is a clinical entity considered an extended Neurofibromatosis phenotype generally caused by different types of intragenic mutations at the NF1 gene. About 5%-10% of patients with neurofibromatosis diagnosis carry chromosomal microdeletions involving NF1, often presenting with a more severe phenotype than that observedin the patients carrying intragenic mutations; however, anticipating the presence of a deletion based only in the phenotype is not straightforward. Patient and Methods: Here we investigated by oligoarray-CGH (aCGH) the presence of a submicroscopic genomic rearrangement in a patientwith a clinical picture of Neurofibromatosis, and other characteristics compatible with Noonansyndrome. Results: The aCGH analysis revealed a germline de novo ~1.3 Mb microdeletion at 17q11.2 encompassing other coding genes besides the NF1 gene. Discussion: Up to now, thenumber of reported patients with Neurofibromatosis-Noonan syndrome carrying NF1 microdeletions is quite small. The continuous identification of patients carrying 17q11.2 deletions canhelp to establish a reliable genotype-phenotype relationship in this syndrome

The fragile x-associated tremor and ataxia syndrome (FXTAS) / A síndrome de tremor e ataxia associada ao X frágil (FXTAS)

FXTAS (Fragile X-associated tremor and ataxia syndrome) is a late- onset neurodegenerative disorder affecting mainly men, over 50 years of age, who are carriers of the FMR1 gene premutation. The full mutation of this gene causes the fragile X syndrome (FXS), the most common cause of inherited mental retardation. Individuals affected by FXTAS generally present intention tremor and gait ataxia that might be associated to specific radiological and/or neuropathological signs. Other features commonly observed are parkinsonism, cognitive decline, peripheral neuropathy and autonomic dysfunction. Nearly a decade after its clinical characterization, FXTAS is poorly recognized in Brazil. Here we present a review of the current knowledge on the clinical, genetic and diagnostic aspects of the disease.

A FXTAS (síndrome de tremor e ataxia associada ao X frágil) é uma doença neurodegenerativa de início tardio que afeta principalmente homens acima dos 50 anos de idade, portadores de pré-mutação do gene FMR1. A mutação completa desse gene é responsável pela síndrome do cromossomo X frágil (SXF), a causa mais comum de deficiência mental herdada. Indivíduos afetados pela FXTAS geralmente apresentam tremor de intenção e ataxia de marcha que podem estar associados a sinais radiológicos ou neuropatológicos específicos. Outras características comumente observadas são parkinsonismo, declínio cognitivo, neuropatia periférica e disfunções autonômicas. Quase uma década após sua caracterização clínica, a FXTAS é mal conhecida por médicos no Brasil. Esta revisão apresenta o conhecimento atual sobre os aspectos clínicos, genéticos e diagnósticos da síndrome.