Evaluation of Targeted Therapies Currently Available for Congenital Genetic Conditions Indexed in <scp> <i>GeneReviews</i> </scp>

In this study, we propose a definition of targeted therapy and use GeneReviews, a peer-reviewed, online point-of-care resource for primarily constitutional (or rare congenital mosaic) genetic conditions, to compile a list of primarily heritable genetic disorders for which such targeted therapy is available. This study aims to give a high-level view of the types of targeted therapies and the proportion of congenital genetic disorders for which a targeted therapy is available. We propose that a targeted therapy is one that addresses the underlying molecular mechanism of the disorder and/or can alter the disease course (including by providing a cure in some instances) but may not be an obvious treatment option without knowledge of the patient's underlying genetic condition. For the purposes of this study, a treatment meeting one or both of these criteria was categorized as targeted. This means that the clinician might not consider the specific treatment option unless the patient was known to have the genetic diagnosis. This definition does not include therapies based on symptoms alone, which does not rely on the clinician being aware of a patient's genetic diagnosis. As most of the congenital genetic conditions in this study are rare and often diagnosed in a pediatric age group, determining efficacy for the specific use of most of the targeted therapies is not possible, although any drug or medication in the Management section of GeneReviews is approved by the Food and Drug Administration (FDA), with rare exceptions for drugs approved by the European Medicines Agency (EMA) of the European Union (EU) but not yet FDA approved. Of 790 GeneReviews chapters on primarily constitutional genetic conditions included in this study, 176 chapters representing over 255 genes meet the definition of having a targeted therapy.