ndrome caused by heterozygous mutations in the genes encoding type I or II transforming growth factor-b (TGF-beta) receptor. An increase in TGF-beta signaling results in phenotypes closely resembling Marfan syndrome, Marfanoid craniosynostosis syndrome (Shprintzen-Goldberg syndrome), and vascular Ehlers-Danlos syndrome.
Two subtypes of Loeys-Dietz syndrome have been delineated. Loeys-Dietz syndrome type I patients have both craniofacial and vascular disorders. The most characteristic craniofacial findings are hypertelorism and broad or bifid uvula or cleft palate, two of the three components of the clinical triad that also includes arterial aneurysms and tortuosity. In contradistinction, Loeys-Dietz syndrome type II patients may have a bifid uvula but do not have a cleft palate, craniosynostosis, or hypertelorism.
Surgical intervention is needed and death occurs at a later age in Loeys-Dietz syndrome type II than in Loeys-Dietz syndrome type I patients. Infact, the cardiovascular outcome of Loeys-Dietz syndrome can be predicted by a “craniofacial severity index” that is based on presence of cleft palate and craniosynostosis, the degree of increased intraocular distance, and the uvular configuration.
Additional manifestations of Loeys-Dietz syndrome include blue sclera, malar hypoplasia, exotropia, and retrognathia. Cervical spine instability, pectus deformity, arachnodactyly, craniosynostosis, scoliosis, and joint laxity are some of the many musculoskeletal manifestations. The pronounced tortuosity of the arteries in Loeys-Dietz syndrome is a finding not frequently identified in the general population. Aneurysms have been identified throughout the arterial system, with an increased propensity for rupture or dissection. In addition, Loeys-Dietz syndrome patients may be afflicted with congenital cardiac anomalies.
