Etiological diagnosis of macroglossia: Systematic review and diagnostic algorithm

The objective of this literature review was to list the different etiologies of macroglossia reported in the literature, to identify characteristics that might guide diagnosis, and to create a diagnostic algorithm. The bibliographic search was carried out between October 2019 and July 2020 in the PubMed research base using the keywords “macroglossia” (MESH) and/or “tongue enlargement”. Of the 1711 references identified, 615 articles were excluded, and 1096 abstracts were reviewed. We classified the different etiologies identified according to their mechanism and whether they were congenital or acquired. The etiologies are divided into the following categories: genetic malformation syndromes, non-syndromic congenital malformations, endocrinopathies, neuromuscular diseases, storage disorders, infectious, inflammatory, traumatic, and iatrogenic diseases. Based on this review, we propose a diagnostic algorithm for macroglossia according to the characteristics described. The most common diagnoses among acquired causes were amyloidosis (13.7%), endocrinopathies (8.8%), myopathies (4%) and tongue tumors (6.7%). The most common congenital causes were aneuploidy, lymphatic malformations, and Beckwith-Wiedemann syndrome, which is the main cause of congenital macroglossia, even if it appears isolated.