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Supravalvular aortic stenosis (SVAS) is a congenital narrowing of the ascending aorta which can occur sporadically, as an autosomal dominant condition, or as one component of Williams syndrome. SVAS is caused by translocations, gross deletions and point mutations that disrupt the elastin gene (ELN) on 7q11.23. Functional hemizygosity for elastin is known to be the cause of SVAS in patients with gross chromosomal abnormalities involving ELN. However, the pathogenic mechanisms of point mutations are less clear. One hundred patients with diagnosed SVAS and normal karyotypes were screened for mutations in the elastin gene to further elucidate the molecular pathology of the disorder. Mutations associated with the vascular disease were detected in 35 patients, and included nonsense, frameshift, translation initiation and splice site mutations. The four missense mutations identified are the first of this type to be associated with SVAS. Here we describe the spectrum of mutations occurring in familial and sporadic SVAS and attempt to define the mutational mechanisms involved in SVAS. SVAS shows variable penetrance within families but the progressive nature of the disorder in some cases, makes identification of the molecular lesions important for future preventative treatments.

Complications of Bacillus Calmette-Guerin (BCG) vaccination have been reported in immunocompetent as well as in immunocompromised individuals. Severe and/or late complications have been associated with impairment of cell-mediated immunity. A case of BCG lymphadenitis in a vertically infected HIV-positive boy 9.5 years after vaccination is presented. The vaccination was performed within the first week of life, the HIV status of the mother being unknown. When the boy was 2.5 years old, his HIV infection was diagnosed after his mother had died from AIDS. At that time his CD4 count was 739 cells/microL. In the course of the following years, his CD4 count declined steadily, until it reached a low of about 20 cells/microL at the age of 5.5 years. He was troubled with recurring respiratory infections and one incidence of severe pancreatitis. Apart from that, he was in stable condition and led a more or less normal life. At the age of 9.5 years he developed lymphadenitis in his left axilla. The node was examined via biopsy, and the appropriate tests showed an infection with Mycobacterium bovis BCG variety. The CD4 count at that time was 16 cells/microL, polymerase chain reaction showed 220,000 RNA copies/mL. There were no signs of dissemination. Antitubercular agents were administered, and an antiretroviral combination therapy was started. The patient was discharged from the hospital after approximately 2 months. After an uneventful period of 9 months, the boy, still on antitubercular medicine, exhibited a secreting fistula in his left axilla, again due to Mycobacterium bovis, BCG variety. The fistulous tissue was removed surgically, and the antitubercular treatment was given intravenously for almost 3 months before being changed to an oral application. In addition, the antiretroviral regimen was completely exchanged. The case presented illustrates that there is a risk of very late complications in HIV-infected individuals, even when they are vaccinated when they are asymptomatic newborns. Although the risk seems low, one has to be aware of the problem because timely treatment is probably essential to prevent dissemination of the infection. Late complications of BCG vaccinations are most likely to be detected in countries with high medical standards, where HIV-infected children are surviving for longer periods of time.

Congenital complete atrioventricular block is a rare entity. The association between this disease, maternal connective tissue disease and maternal antibodies [anti-Ro (SS-A) resp. anti-La (SS B)] is well known. Diagnosis can be made by means of fetal Doppler-echocardiography by the 16th week of gestation. In our case diagnosis was established in the 21st week of gestation. Ventricular rate was 55/min, atrial rate 70/min. There were no signs of fetal hydrops. There were no signs of maternal connective tissue disease, but anti-Ro and anti-La antibodies could be detected. The mother was treated with steroids from the time of diagnosis until the end of pregnancy. Altogether 9 Doppler-echocardiographic studies were performed. A recurrence of normal rhythm did not occur. A slow but continuous decrease of atrial and ventricular rate was observed. Interestingly, there was no development of fetal hydrops until the very end of pregnancy when the fetal heart rate reached a low of 28 beats per minute. We speculate, that the therapy with steroids might have played an important role in the prevention of early hydrops. At the onset of fetal hydrops delivery should be considered. In symptomatic complete atrioventricular block we prefer the implantation of a permanent pacemaker system immediately after birth. Efficient care for the fetus resp. the newborn can only be achieved through well planned cooperation.

Objective: Closure of the fetal ductus arteriosus, which is usually due to nonsteroidal antiinflammatory agents, may be detrimental. Therefore prenatal and postnatal clinical and echocardiographic findings in four human fetuses with spontaneous ductus arteriosus occlusion are reported., Study Design: Echocardiographic and clinical data were retrospectively analyzed., Results: Spontaneous closure of the ductus arterious was discovered in four fetuses (gestational age 34 to 38 weeks). No mother had received nonsteroidal antiinflammatory agents. Enlargement of the right heart and pulmonary arteries and tricuspid and pulmonary regurgitation were present in all cases. Two fetuses had right ventricular hypertension. Postnatally their right ventricular function recovered promptly. The others had severe right heart failure with abnormal umbilical venous pulsations. After immediate delivery none had signs of persistent pulmonary hypertension. However, they have echocardiographic evidence of right ventricular dysfunction 2 to 6 months after delivery., Conclusions: Occlusion of the fetal ductus arteriosus may also occur in the absence of treatment with nonsteroidal antiinflammatory agents. Immediate delivery resulted in good clinical outcome, although right ventricular dysfunction may persist.

From September 1992 to the end of August 1993 we treated fourteen children who suffered from rhesus hemolytic disease with high-dose intravenous immune globulin G. Eleven patients did not require an exchange transfusion, three needed an exchange transfusion despite immune globulin therapy. Although an exchange transfusion cannot be avoided in all patients, this new method is an important addition to the currently available possibilities of treatment. It is without adverse side effects and helps to lower the number of exchange transfusions.