Genetic causes of lymphatic disorders: recent updates on the clinical and molecular aspects of lymphatic disease

Abstract

Purpose of review The lymphatic system facilitates several key functions that limit significant morbidity and mortality. Despite the impact and burden of lymphatic disorders, there are many remaining disorders whose genetic substrate remains unknown. The purpose of this review is to provide an update on the genetic causes of lymphatic disorders, while reporting on newly proposed clinical classifications of lymphatic disease. Recent findings We reviewed several new mutations in genes that have been identified as potential causes of lymphatic disorders including: MDFIC, EPHB4, and ANGPT2. Furthermore, the traditional St. George's Classification system for primary lymphatic anomalies has been updated to reflect the use of genetic testing, both as a tool for the clinical identification of lymphatic disease and as a method through which new sub-classifications of lymphatic disorders have been established within this framework. Finally, we highlighted recent clinical studies that have explored the impact of therapies such as sirolimus, ketoprofen, and acebilustat on lymphatic disorders. Summary Despite a growing body of evidence, current literature demonstrates a persistent gap in the number of known genes responsible for lymphatic disease entities. Recent clinical classification tools have been introduced in order to integrate traditional symptom- and time-based diagnostic approaches with modern genetic classifications, as highlighted in the updated St. George's classification system. With the introduction of this novel approach, clinicians may be better equipped to recognize established disease and, potentially, to identify novel causal mutations. Further research is needed to identify additional genetic causes of disease and to optimize current clinical tools for diagnosis and treatment.