Overgrowth Syndromes: Genetics and Clinical Challenges for Diagnosis And Management

Overgrowth syndromes are a heterogeneous group of rare disorders characterized by generalized or segmental excessive growth commonly associated with additional features, including visceromegaly, macrocephaly, intellectual disability, and behavior/psychological-specific profiles. A large proportion of these conditions is caused by pathogenic variants in genes with function in epigenetic regulation, and/or with a role in cell proliferation and development. Reaching diagnosis in overgrowth syndromes is a hard task due to the clinical overlap of the disorders so molecular confirmation is mandatory. Massive parallel sequencing and DNA methylation profiling have become powerful tools in the clinical setting to properly diagnose overgrowth syndromes. Management of these disorders is also a challenging task, requiring a multidisciplinary approach that, besides tumor risk surveillance, should take into account both neuropsychological aspects, and proper care and monitoring of the additional problems.

This research topic aims to provide an updated overview of the main clinical areas related to overgrowth syndrome diagnosis, management, and surveillance protocols and guidelines. Aspects related to the mechanisms of disease and involved pathways are also relevant. Due to their genetic heterogeneity and clinical overlap, the use of complementary omics can significantly improve the diagnostic yield. Many overgrowth syndromes may present with an increased risk of cancer; for this reason, syndrome-specific tumor screening protocols have recently been established for a restricted set of these disorders. Many individuals with overgrowth syndrome diagnosis survive to adulthood; adult-onset signs and natural history also represent relevant topics. We encourage articles reporting on the genetic/clinical delineation of poorly characterized overgrowth syndromes, differential diagnosis, experimental workflow/strategies dedicated to the functional validation of clinically unclassified variants, large cohort series descriptions, and longitudinal studies for surveillance of clinical course and natural history.

We are particularly interested in original articles and reviews addressing the following topics:
1. genetics of overgrowth syndromes, and genotype-phenotype correlation studies;
2. clinical characterization of poorly characterized overgrowth syndromes and reports on new phenotypes;
3. functional validation/classification of clinically unclassified variants in genes implicated in overgrowth syndromes;
4. natural history and large cohort series;
5. guidelines and management protocols;
6. transition medicine and adult-onset signs.