Lateralized overgrowth (LO), or segmental overgrowth, is defined as an increase in tissue growth of various origins (skeletal, muscular, fibrous, vascular, adipose, or any association of these) in any region of the body.
Congenital disorders of lateralized or segmental overgrowth (LO) are heterogeneous conditions with increased tissue growth in a body region. LO can affect every region, be localized or extensive, involve one or several embryonic tissues, showing variable severity, from mild forms with minor body asymmetry to severe ones with progressive tissue growth and related relevant complications. Recently, next-generation sequencing approaches have increased the knowledge on the molecular defects in LO, allowing classifying them based on the deranged cellular signaling pathway. LO is caused by either genetic or epigenetic somatic anomalies affecting cell proliferation. Most LOs are classifiable in the Beckwith–Wiedemann spectrum (BWSp), PI3KCA/AKT-related overgrowth spectrum (PROS/AROS), mosaic RASopathies, PTEN Hamartoma Tumor Syndrome, mosaic activating variants in angiogenesis pathways, and isolated LO (ILO). These disorders overlap over common phenotypes, making their appraisal and distinction challenging.
|Cardinal Features (2 Points Each)||Suggestive Features (1 Point Each)|
|Macroglossia||Macrosomia (height/Birth Weight > +2SD)|
|Exomphalos||Facial naevus simplex|
|Multifocal/bilateral Wilms tumor or Nephroblastomatosis||Ear creases/pits|
|Pathology findings:||Typical BWSp tumors (neuroblastoma, rhabdomyosarcoma, unilateral WT, hepatoblastoma, adrenocortical carcinoma, phaeochromocytoma)|
|Adrenal cortex cytomegaly||Nephromegaly/Hepatomegaly|
|Placental mesenchymal dysplasia||Umbilical hernia/Diastasis recti|