Open AccessMissed diagnoses: Clinically relevant lessons learned through medical mysteries solved by the Undiagnosed Diseases Network
Author(s) -
Cope Heidi,
Spillmann Rebecca,
Rosenfeld Jill A.,
Brokamp Elly,
Signer Rebecca,
Schoch Kelly,
Glanton Emily,
Sullivan Jennifer A.,
Macnamara Ellen,
Lincoln Sharyn,
GoldenGrant Katie,
Orengo James P.,
Clark Gary,
Burrage Lindsay C.,
Posey Jennifer E.,
Punetha Jaya,
Robertson Amy,
Cogan Joy,
Phillips John A.,
MartinezAgosto Julian,
Shashi Vandana
Publication year - 2020
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.1397
Subject(s) - medical diagnosis , genetic diagnosis , genetic testing , medicine , genetic counseling , genomics , exome sequencing , exome , identification (biology) , disease , bioinformatics , data science , computer science , genome , pathology , phenotype , genetics , gene , biology , botany
Background Resources within the Undiagnosed Diseases Network (UDN), such as genome sequencing (GS) and model organisms aid in diagnosis and identification of new disease genes, but are currently difficult to access by clinical providers. While these resources do contribute to diagnoses in many cases, they are not always necessary to reach diagnostic resolution. The UDN experience has been that participants can also receive diagnoses through the thoughtful and customized application of approaches and resources that are readily available in clinical settings. Methods The UDN Genetic Counseling and Testing Working Group collected case vignettes that illustrated how clinically available methods resulted in diagnoses. The case vignettes were classified into three themes; phenotypic considerations, selection of genetic testing, and evaluating exome/GS variants and data. Results We present 12 participants that illustrate how clinical practices such as phenotype‐driven genomic investigations, consideration of variable expressivity, selecting the relevant tissue of interest for testing, utilizing updated testing platforms, and recognition of alternate transcript nomenclature resulted in diagnoses. Conclusion These examples demonstrate that when a diagnosis is elusive, an iterative patient‐specific approach utilizing assessment options available to clinical providers may solve a portion of cases. However, this does require increased provider time commitment, a particular challenge in the current practice of genomics.