Genetic counseling in congenital heart disease.

Recommendations for the general practitioner would-include answering parents' questions with some of the information in this article in mind, outlining that although the defect did occur, for most individuals, there is no identifiable cause. This may or may not be helpful to the parents, but it is the current state of knowledge at this time. It would never be proper to tell a family that the defect could never happen again, but for the majority of parents who have given birth to a child with a single isolated heart defect, the chances are fairly high that the next child will not have a heart defect. If there is significant concern about a current pregnancy, a fetal echocardiogram can provide important information. The presence of a cardiac defect in and of itself constitutes a major birth defect and should stimulate the search for other problems. When other anomalies are found and an identifiable syndrome is present, then care of the infant is dictated by the heart defect along with other features of the syndrome. Of note, when a syndrome that frequently has a heart defect in its spectrum of anomalies is identified, it is quite reasonable to perform a thorough cardiovascular evaluation to determine whether a cardiac defect is present. For example, all children with Down syndrome should have a thorough cardiac evaluation early in life, including a cardiac ultrasound. Knowledge about the genetics and etiology of cardiac defects is changing yearly. By the end of the decade, it is expected that more information will be available for physicians to pass on to the families of children born with congenital heart defects.

Cardiovascular malformations in Smith-Lemli-Opitz syndrome.

We reviewed 215 patients (59 new, 156 from the literature) with Smith-Lemli-Opitz syndrome (SLOS), and found that 95 (44%) had a cardiovascular malformation (CVM). Classifying CVMs by disordered embryonic mechanisms, there were 5 (5.3%) class 1 (ectomesenchymal tissue migration abnormalities), 56 (58.9%) class II (abnormal intracardiac blood flow), 25 (26.3%) class IV (abnormal extracellular matrix), and 5 (5.3%) class V (abnormal targeted growth). Comparing the frequencies of individual CVMs in this series with a control group (the Baltimore-Washington Infant Study), there were 6 individual CVMs which showed a significant difference from expected values. When frequencies of CVMs in SLOS were analyzed by mechanistic class, classes IV and V were significantly more frequent, and class I significantly less frequent, than the control group. Although CVMs in SLOS display mechanistic heterogeneity, with an overall predominance of class II CVMs, the developmental error appears to favor alteration of the cardiovascular developmental mechanisms underlying atrioventricular canal and anomalous pulmonary venous return. This information should assist the clinical geneticist evaluating a patient with possible SLOS, and should suggest research direction for the mechanisms responsible for the SLOS phenotype.

Evaluation of remote stethoscopy for pediatric telecardiology.

OBJECTIVE: To investigate the interobserver reliability and diagnostic validity of a commercial electronic stethoscope for pediatric telecardiology. MATERIALS AND METHODS: Pairs of blinded pediatric cardiologists made independent diagnoses, recommendations concerning follow-up echocardiography, and specific judgments regarding heart sounds, murmurs, and congenital heart disease using an electronic (ES) or an acoustic (AS) stethoscope on 78 pediatric cardiology outpatients and at a distance of 450 km (280 miles) with 38 telemedicine cardiology outpatients. The kappa statistic (K) indexed the instruments' interexaminer reliabilities. The validity of ES was measured by K for ES versus AS and by the percentage of cases where the findings for ES and AS differed sufficiently to suggest an important ES screening error. RESULTS: For heart disease, AS, ES, and tele-ES reliabilities were satisfactory (K = 0.80, 0.67, and 0.80, respectively), as were AS agreement with hands-on ES (K = 0.65) and with tele-ES (K = 0.64). The AS and ES reliabilities and ES/AS agreement were also satisfactory for systolic regurgitant and diastolic pulmonic murmurs (K = 0.63-0.78) but were unsatisfactory for evaluable heart sounds and other murmurs (K = 0.16-0.60). The ES yielded clinically important disagreements with AS in 5.4% of the clinic cases and 10.5% of the telemedicine cases (P = 0.67). In determining the need for additional work-up (echocardiography) or follow-up appointments, hands-on ES and tele-ES had a combined accuracy of 92%, with a sensitivity of 88% and a specificity of 97%. CONCLUSIONS: Hands-on ES provided reliable and valid screening for congenital heart disease. Tele-ES was highly reliable but had reduced diagnostic validity. Examiner blinding, bandwidth limitations, and artificial restrictions on the remote assistant may have contributed to this reduced performance. As these factors are easily correctable, we regard the ES as a highly promising tool for pediatric telecardiology.

Balloon pulmonary valvuloplasty for isolated pulmonary valvular stenosis.

Fifteen balloon pulmonary valvuloplasties (BPVs) were performed on 13 infants and children with isolated pulmonary valvular stenosis (PVS). There were no complications. Two patients required repeat BPV, one for failure, the other for restenosis. At the time of the 13 latest BPVs, age ranged from three days to 13.1 years (mean 5.7 +/- SD 4.8 years). Average Doppler pulmonary valve pressure gradient preceding BVP was 75 +/- 22 mm Hg. At follow-up it was 25 +/- 9 mm Hg (p < .0001). Follow-up interval was 0.61 to 4.70 years (2.29 +/- 1.18). Restenosis occurred in 1/13 (8%) of the patients. The remaining 12/13 (92%) showed highly satisfactory sustained gradient reductions. Doppler gradients preceding BPV by as much as 4 months correlated highly with catheter gradients at time of BPV, confirming that Doppler echocardiography is a highly accurate indication of PVS severity. Catheterization for PVS should therefore not be used for diagnostic purposes alone. BPV can be performed safely, economically and effectively and is recommended as the treatment of choice for infants and children with moderate to severe isolated PVS. For very young patients, follow-up Doppler surveillance should be done semi-annually; for all others, annually.

Cerebrovascular stenoses with cerebral infarction in a child with Williams syndrome.

We report on a patient with Williams syndrome who suffered a cerebrovascular accident. Clinical evaluation demonstrated the presence of carotid and cerebral arterial stenoses. We believe these lesions led to acute cerebrovascular ischemia and a non-hemorrhagic cerebral infarction. It is possible the stenoses were exacerbated by a vasculitis. The stenoses were identified by both invasive and noninvasive imaging studies. These studies may have a role in the evaluation of persons with Williams syndrome.

Linkage analysis of autosomal dominant atrioventricular canal defects: exclusion of chromosome 21.

The association between trisomy 21 and a high incidence of atrioventricular canal defects (AVCDs) indicates that a locus on chromosome 21 is involved in this congenital heart defect. We have investigated whether a genetic locus on chromosome 21 is also involved in familial nonsyndromic AVCDs. Short tandem repeat polymorphisms (STRPs) from chromosome 21 were used for linkage analysis of a family having multiple members affected with AVCDs. In this family, the gene for AVCDs is transmitted as an autosomal dominant with incomplete penetrance. The affected family members are nonsyndromic and have normal karyotypes. Two-point and multipoint linkage analyses produced significantly negative LOD scores for all informative markers. A comparison of the overlapping exclusion distances obtained for each marker at LOD equal -2.0 with the 1000:1 consensus genetic map of the markers, excludes chromosome 21 as the genetic location for AVCDs in this family. The exclusion of chromosome 21 indicates that another gene, not located on chromosome 21, is involved in atrioventricular canal defect formation.

Terminal deletion of 7q presenting in utero with a truncus arteriosus and nonimmune hydrops.

Terminal deletion of 7q presents with variable anatomical and developmental findings. This case is the first reported in utero diagnosis based on cytogenetic findings and in utero demonstration of resolving congestive heart failure due to a truncus arteriosus.

Pediatric cardiology: auscultation from 280 miles away.

New long-distance audio/video and data communications links among health-care facilities promise to reduce rural patients' travel time and waiting time for subspecialty consultations. To offer a satisfactory alternative to face-to-face examination, the long-distance system must meet the subspecialty's minimum criteria. For pediatric cardiology in particular, the system has to permit satisfactory cardiac auscultation. A preliminary test of remote auscultation that uses an electronic stethoscope involved two pediatric cardiologists, one listening hands-on with an acoustic stethoscope, the other listening independently at long distance with the electronic instrument. Taking the acoustic findings as the reference standard, the electronic stethoscope did not miss the one case of heart disease, correctly recommended echocardiogram follow-up in the two cases requiring it, and agreed on 80% of the murmurs' qualitative specifics. The patients' parents also indicated that the system was highly acceptable. We are following up these results with a full-scale study of the effectiveness and parental acceptance of remote auscultation.

Twenty-eight loci form a continuous linkage map of markers for human chromosome 1.

We have used a combination of 30 serological, protein electromorphic, and DNA markers defining 28 loci to construct a linkage map of chromosome 1. These markers form a continuous linkage group of 320 cM in males and 608 cM in females; female genetic distances were on average twofold higher than those of males across the map. Among the DNA markers are 10 highly polymorphic markers reflecting loci that contain a variable number of tandem repeats, well distributed over the length of the chromosome, that will be highly efficient anchor points for application of this map to studies of human genetic disease.