An introduction to standardized clinical nomenclature for dysmorphic features: the Elements of Morphology project

Human structural malformations (anomalies, or birth defects) have a broad and complex range of manifestations and severities. The description of these findings can be challenging because the variation of the features is continuous and only some of them can be objectively assessed (that is, measured). Additionally, different specialties (embryologists, developmental biologists, surgeons, clinical geneticists, and so on) have developed descriptors for these findings that are based either on mechanistic, etiologic, or management considerations, and are thus laden with meaning, which can be invalidated by changing knowledge. Some terms have disparate definitions even within a specialty. Finally, a number of terms previously in common clinical use were disparaging (mongoloid slant, arachnodactyly, devil ear, and so on) and needed to be replaced with more neutral terms.The need to develop such a set of terms is driven by the ever-increasing throughput of biological methods, which are outstripping the ability of clinical analyses to properly phenotype patients for both research and clinical care. The processes of the elucidation of the etiology of these disorders can be represented as a pipeline of varying caliber, where the diameter of the pipe represents the throughput of the process. In the late 1980 s and early 1990 s, the limiting factors were entirely molecular: it was much more difficult and slow to genotype and map disorders, find genes within candidate regions and sequence them than it was to identify and clinically analyze the patients (Figure 1a). With the completion of the human genome project, physical mapping could be performed by interrogating a web browser (Figure 1b). Soon after, high throughput capillary sequencing and single nucleotide polymorphism (SNP) marker typing methods improved to lessen those impediments. Finally, with the advent of chip-based genotyping with > 106 features and next generation sequencing, molecular process throughputs are massive