Research advancements in the clinical characteristics and pathogenic genes of LADD syndromeOA

LADD syndrome(lacrimo-auriculo-dento-digital syndrome,OMIM 149730)is a rare autosomal dominant genetic disorder,also known as Levy-Hollister syndrome.It is characterized by multi-organ abnormalities with interindividual variability.The core phenotypes involve multiple systems.In terms of ocular manifestations,71%of patients present with lacrimal gland hypoplasia/agenesis,50%with lacrimal punctum anomalies,and 71.4%with nasolacrimal duct obstruction;additional conditions such as corneal disorders and glaucoma may also occur.Ear anomalies include"cup ear"deformity,low-set ears,and hearing loss(affecting 59.1%of patients,mostly mild to moderate).Oral manifestations encompass enamel hypoplasia,microdontia,and salivary gland hypoplasia—with 65.7%of patients experiencing xerostomia during childhood.Rarely,urogenital,neurological,or pulmonary anomalies may develop.Pathogenically,the disease is caused by heterozygous mutations in fibroblast growth factor receptor 2(FGFR2,the most common causative gene,particularly the IIIb subtype),FGFR3,or FGF10,which disrupts the FGF signaling pathway.Differential diagnosis can be performed based on phenotypic features and genetic testing.This study retrospectively analyzed clinical cases to systemize the phenotypes and pathogenic mechanisms of LADD syndrome,thereby deepening the understanding of its early diagnosis and future treatment strategies.