Coexistence of supravalvular aortic stenosis and osteogenesis imperfecta.

A 54 year old woman was admitted for cardiac catheterisation. She had-been attending the outpatient clinic since 1975, with regular review. She had diagnoses of type I osteogenesis imperfecta, and of supravalvular aortic stenosis. Osteogenesis imperfecta was diagnosed in early life on clinical grounds including the presence of blue sclerae and the occurrence of several bone fractures secondary to minimal trauma. A number of family members have been diagnosed with the same condition (figure 1-family pedigree). The supravalvular aortic stenosis was not diagnosed until later. She was initially referred to the cardiology clinic for further evaluation following the discovery of a systolic murmur during routine examination at an antenatal clinic. Echocardiography revealed a morphologically normal aortic valve and confirmed the presence of supravalvular aortic stenosis, with an estimated peak systolic gradient of 20 mmHg. Examination of her family history has also revealed several members with a diagnosis of supravalvular aortic stenosis (Figure). Neither of her parents was known to have had the disease, but her mother had died prematurely at the age of 42 years supposedly due to asthma. There are three family members diagnosed with both osteogenesis imperfecta and supravalvular aortic stenosis. Therefore, some members of this family have either supravalvular aortic stenosis or osteogenesis imperfecta, some have both diseases and some have neither. Cardiac catheterisation (SVAS) revealed normal coronary arteries and left ventricular function. There was narrowing of the ascending aorta immediately above the aortic valve with poststenotic dilatation of the aorta, giving the typical "hourglass" appearance seen in SVAS. There was a peak-to-peak gradient of 40 mmHg across the lesion on catheter pull-back. Karyotyping revealed a normal XX pattern with no deletion evident. The mutation causing SVAS in this family has been mapped to the elastin gene on chromosome 7. This family has not yet been investigated with regard to the molecular basis for theirosteogenesis imperfecta. DISCUSSION Supravalvular aortic stenosis is defined as an obstructive vascular disease due to severe narrowing of large elastic arteries, particularly the ascending aorta, and including the pulmonary, coronary and carotid arteries. The incidence of the disease is estimated at I in 20,000 births. The large majority of cases are familial, with transmission of the disease in an autosomal dominant manner'. The disease is caused by mutation in the elastin gene (ELN), located at chromosome 7qll.232. Supravalvular aortic stenosis is also a common feature of Williams' syndrome, a congenital multisystem disorder caused …