Medical case reports in the age of genomic medicine

Abstract

The case report has been a pillar of medical literature but has been displaced recently because of inherent risks of bias. As we move towards precision medicine, however, the case report format could provide an important method for describing disease mechanisms based on rare genetic variants. Empirical evidence reveals that many previously unexplained Mendelian diseases are accounted for by rare heterozygous alleles, de novo mutations or compound heterozygous mutations, and that disease-associated variants are often confined to the kindred of the affected individual. Elucidation of the phenotypes of these rare genetic variants will necessarily offer unique insights into disease mechanisms. Even when the association between variants in a specific gene and a disease has already been identified, individual cases are valuable. Allelic series extend both the clinical and laboratory phenotypes. Finally, the prevalence of a disease is not a reliable indicator of the therapeutic importance of the underlying mechanism, so resolving extreme phenotypes even in single cases has the potential to identify new treatment strategies relevant to more common disease.

Agreement between results of meta-analyses from case reports and clinical studies, regarding efficacy and safety of idursulfase therapy in patients with mucopolysaccharidosis type II (MPS-II). A new tool for evidence-based medicine in rare diseases

“…The low prevalence of rare diseases, the phenotype heterogeneity and the long latency period, may prevent and/or make the possibility of performing randomized clinical trials (RCTs) and large studies extremely difficult [1, 2]. Therefore, with these diseases, knowledge of treatment efficacy or any other type of clinical knowledge must be based only on observational studies, rare disease registries and case reports [2], where real world data and evidence play an important role in health care decisions [3].…”

“…Therefore, with these diseases, knowledge of treatment efficacy or any other type of clinical knowledge must be based only on observational studies, rare disease registries and case reports [2], where real world data and evidence play an important role in health care decisions [3]. However, RCTs are assessed, in evidence-based medicine as the best corroboration of the efficacy of new treatments, while case reports show a lower grade level of evidence [1].…”

The Value of Case Reports in Systematic Reviews from Rare Diseases. The Example of Enzyme Replacement Therapy (ERT) in Patients with Mucopolysaccharidosis Type II (MPS-II)

“…Different authors have underlined the impact of individual clinical reports' results in clinical practice and research [11,72]. Previous studies and guidelines have suggested the inclusion of case reports in systematic reviews, but they did not consider the exclusion of case reports a serious concern if there are other designs available with a higher grade of evidence than case reports [12,69].…”

Unusual Association of Two Germline Rearrangements in CDC73/HRPT2 Gene: Complexity of Clinical Counseling in the Age of Genomic Medicine

“…It thus raises the issue of genetic counseling complexity for these incidental events not yet reported in publications and emphasizes the importance of multidisciplinary support. Literature should collect such data about these complex genetic events to create a medical bank [16,17], as described by Aronson, et al [18], to which refer to regarding the patient support, genetic counseling and medical monitoring of associated pathologies. In conclusion, our work describes for the first time the association of two genetic rearrangements affecting CDC73 gene.…”