AORTIC REGURGITATION Cardiovascular involvement in osteogenesis imperfecta

While aortic root dilatation and valvular dysfunction have been well-documented in osteogenesis imperfecta (01), the nature and extent of cardiovascular involvement in 01 have not been clearly delineated. A clinical and echocardiographic survey involving 109 individuals with various nonlethal 01 syndromes from 66 separate families was undertaken. Clinically discernible valvular dysfunction was encountered in only four of the 109 individuals (aortic regurgitation in two, aortic stenosis in one, and mitral valve prolapse in one), none of whom were related. Aortic root dilatation was recognized echocardiographically in eight (12.1%) of 66 individuals comprising a subset of the sample in which each family was represented by a single individual. The extent of the aortic root dilatation was mild (the largest dimension measuring 4.3 cm) and was unrelated to the age of the individual. Dilatation was seen in each of the different 01 syndromes but was strikingly segregated within certain families (p < .001). In the same subset of 66 individuals, mitral valve prolapse was encountered in two or 6.9% of the 29 individuals aged 15 years or greater in whom adequate studies were obtained. This observed frequency was not different from that seen in a normal adult population. Aortic root dilatation appears to represent a distinct phenotypic trait in patients with 01 that is nonprogressive and occurs in about 12% of affected individuals. Whether mitral valve prolapse should be considered as a part of the cardiovascular phenotype in 01, or alternately segregates as an independent autosomal dominant trait has yet to be determined. Circulation 73, No. 1, 54-61, 1986. OSTEOGENESIS IMPERFECTA (01) is a group of heritable disorders of the connective tissue.' 2 Although bone fragility is the most widely recognized aspect of the clinical phenotype, the alterations in the connective tissue of affected individuals may be manifest in several extraskeletal tissues, including those of the sclerae, middle and inner ear, tendons and ligaments, integument, dentine, and cardiovascular structures. A considerable clinical and biochemical heterogeneity exists both between and within the different 01 syndromes.3 In the few variants of 01 studied in detail, From the Cardiology Service, Department of Pediatrics, McGill University-Montreal Childrens Hospital Research Institute, and the Department of Epidemiology and Health, McGill University, Montreal; the Departments of Pediatrics and Biochemistry, UMDNJ-Rutgers Medical School, Piscataway, NJ; and the Cardiology Branch, NHLBI, and the Clinical Center, NIH, Bethesda. Address for correspondence: John Hortop, M.D., Cardiology Service, Montreal Childrens Hospital, 2300 rue Tupper, Montreal, Quebec, Canada H3H 1P3. Received June 5, 1985; revision accepted Sept. 19, 1985. Dr. Hortop is a fellow of the Canadian Heart Foundation. Dr. Tsipouras is a recipient of a Clinical Investigator Award (1K08AM01224) of the U.S. Public Health Service. He is also supported by a March of Dimes Clinical Research grant (6-411). *Current address: New England Medical Center, Boston. 54 specific mutations leading to either a quantitative or qualitative defect in type I procollagen synthesis have been delineated.3'4 While serious sequelae of structural alterations in the cardiovascular tissues have been reported infrequently in patients with 01, aortic root dilatation and valvular dysfunction (aortic regurgitation and mitral valve dysfunction) have been well-documented in affected individuals.5' The present study was undertaken to examine the prevalence of aortic root dilatation and valvular dysfunction in the nonlethal 01 syndromes. An analysis of the influence of age, gender, clinical phenotype, and kinship on aortic root dimension provided a further delineation of the nature of the lesion underlying aortic root dilatation in this group of connective tissue disorders. A similar analysis with respect to valvular dysfunction in 01 was limited by the small numbers of individuals with these lesions in our sample. Materials and methods One hundred and nine individuals with 01 from 66 separate families were identified by two of the investigators (P. T. and J. CIRCULATION by gest on N ovem er 6, 2017 http://ciajournals.org/ D ow nladed from PATHOPHYSIOLOGY AND NATURAL HISTORY-AORTIC REGURGITATION