Hand and fibrillin-1 deposition abnormalities in Loeys-Dietz syndrome-expanding the clinical spectrum

摘要

Loeys-Dietz syndrome (LDS) is an autosomal dominant connective tissue disorder characterized by hypertelorism, bifid uvula, cleft palate and arterial tortuosity. We report on a patient with LDS, bearing mutation in the TGFβR2 gene, whose prenatal examination demonstrated clenched fists and club feet, suggesting arthrogryposis multiplex congenita. Postnatal assessment showed digital abnormalities, including brachydactyly, camptodactyly, partial syndactyly and absent distal phalanges. With the lack of fibrillin-1 microfibril deposition as well as impaired and inadequate elastic fiber assembly in our patient's fibroblasts, we speculate that the skeletal abnormalities seen in this patient with LDS are the result of lack of these components in embryonal perichondrium and in blood vessels. We suggest that LDS should be included in the differential diagnosis of joint contractures seen pre and postnatally. Prenatal diagnosis of LDS would be important in parental counseling and early post natal diagnosis could prompt treatment before the development of detrimental vascular complications.