IADR Abstract Archives
Mandibular Condyle Abnormalities Associated With Loeys-Dietz Syndrome, a TGF-β-Opathy
Objectives: Temporomandibular joint disorders (TMDs) affect 4.8% to 42.7% of the United States population, with women affected twice as frequently as men. Loeys-Dietz Syndrome (LDS) is a rare connective tissue disorder caused by autosomal-dominant mutations along the Transforming-growth-factor-beta (TGF-β) pathway, and mainly characterized by aortic aneurysm, mandibular and maxillary hypoplasia, and enamel anomalies. We previously determined that patients with LDS have significant prevalence of TMD, especially LDS Type-I (TGFBR1 mutation) and Type-II (TGFBR2 mutation), potentially related to lower oral health quality of life. The etiology for TMD in LDS has not been studied. Our objective was to investigate the pathogenesis of TMD in LDS.
Methods: A retrospective radiologic analysis of the skeletal morphology of mandibular condyles using CBCTs of 16 patients with LDS (6 males and 6 females under age 40; 2 males and 2 females over age 40) and 16 matched healthy controls was performed. We also used an LDS Type-II mouse model (Tgfbr2G357W/+) that was previously shown to recapitulate the cardiovascular phenotype of LDS. The condylar morphology of Tgfbr2G357W/+ mice and their wild-type littermates was analyzed using micro–CT imaging and histology, at ages 2, 6, 12, and 24 weeks.
Results: Premature or accelerated signs of condylar degeneration, with no predilection for sex, were observed in patients with LDS. Degenerative findings included osteophytes, pseudocysts, and osseous erosion. Bone remodeling (sclerosis, flattening) and significant left/right asymmetries were observed. Tgfbr2G357W/+ mice exhibited degenerative, remodeling, and volumetric changes when compared to the wild-type. Histology of the Tgfbr2G357W/+ mice exhibited degenerative subchondral changes that were not present in the wild-type.
Conclusions: The condyles of patients with LDS demonstrate developmental abnormalities and accelerated degeneration. An LDS mouse model recapitulates this phenotype. These condylar manifestations may explain the high prevalence of TMD in LDS patients, and indicate the critical role of TGF-β signaling in TMJ development and function.
Methods: A retrospective radiologic analysis of the skeletal morphology of mandibular condyles using CBCTs of 16 patients with LDS (6 males and 6 females under age 40; 2 males and 2 females over age 40) and 16 matched healthy controls was performed. We also used an LDS Type-II mouse model (Tgfbr2G357W/+) that was previously shown to recapitulate the cardiovascular phenotype of LDS. The condylar morphology of Tgfbr2G357W/+ mice and their wild-type littermates was analyzed using micro–CT imaging and histology, at ages 2, 6, 12, and 24 weeks.
Results: Premature or accelerated signs of condylar degeneration, with no predilection for sex, were observed in patients with LDS. Degenerative findings included osteophytes, pseudocysts, and osseous erosion. Bone remodeling (sclerosis, flattening) and significant left/right asymmetries were observed. Tgfbr2G357W/+ mice exhibited degenerative, remodeling, and volumetric changes when compared to the wild-type. Histology of the Tgfbr2G357W/+ mice exhibited degenerative subchondral changes that were not present in the wild-type.
Conclusions: The condyles of patients with LDS demonstrate developmental abnormalities and accelerated degeneration. An LDS mouse model recapitulates this phenotype. These condylar manifestations may explain the high prevalence of TMD in LDS patients, and indicate the critical role of TGF-β signaling in TMJ development and function.