Is cystic fibrosis carrier screening cost effective?

Between 2001 and 2005, 6,166 females underwent cystic fibrosis (CF) carrier screening at our institution. Only 36% were Caucasian. We identified 143 carrier females and subsequently tested 85 of their partners. The observed carrier frequency was not significantly different than expected for any racial or ethnic group tested. We identified 6 positive couples (5 Caucasian, 1 Arab American) and 1 affected fetus. In just under 4 years, our institution spent approximately $334,000 on CF population screening. Comparing this to the lifetime medical cost for a CF patient, CF population-based carrier screening is cost effective at our institution, despite the high number of non-Caucasians being screened.

Ectopia lentis and aortic root dilatation in congenital contractural arachnodactyly.

Congenital contractural arachnodactyly (CCA) was described by Beals and Hecht as an autosomal dominant disorder distinct from Marfan syndrome and comprising joint contractures, arachnodactyly, scoliosis, and a distinct "crumpled ear" deformity. While the disorder is similar to Marfan syndrome, it was split from it due to the distinct physical appearance of the patients and, more importantly, the lack of heart and eye findings. Since the original report, several CCA patients have been found to have mitral valve prolapse, structural cardiac anomalies, and occasionally aortic root dilatations similar to those seen in Marfan syndrome. We report on a patient with CCA with bilateral ectopia lentis and aortic root dilatation. Our review of the literature of CCA showed that serial echocardiography and careful eye examinations have not become a standard of medical practice in this condition. Partly this may be due to a lack of documented cases of CCA having severe ectopia lentis and cardiac complications. This patient underscores the need for periodic eye and echocardiographic evaluations of all CCA patients.

Ultrasonographic prenatal diagnosis and fetal pathology of Langer mesomelic dwarfism.

In a family at risk for Langer mesomelic dwarfism, we document the onset of disproportionate growth in the second trimester by sonographic biometry. Midtrimester pathologic correlation of this condition demonstrates primary changes in the growthplate in the regions of proliferating cartilage and hypertrophic and degenerative chondrocytes.

Determinants of altered anxiety after abnormal maternal serum alpha-fetoprotein screening.

With maternal serum alpha-fetoprotein testing, large numbers of previously "low-risk" patients are now considered high risk and are offered genetic testing. Anecdotally, these patients have been perceived as more highly anxious than other second-trimester patients referred for genetic testing because of advanced maternal age. Thus we have studied patient demographics, true genetic risks, the perceptions of risk, and state (situational) and trait (constitutional) anxiety for these patients and their partners. Significantly increased state anxiety was noted for mothers as compared with fathers both in the group of women referred for testing because of maternal serum alpha-fetoprotein levels and in those referred due to advanced maternal age. State anxiety was increased in the women referred for maternal serum alpha-fetoprotein levels as compared with women referred for advanced maternal age. True genetic risks were comparable between the groups. Some critics have argued that maternal serum alpha-fetoprotein screening engenders unnecessary anxiety. Our data show that patients undergoing genetic testing due to maternal serum alpha-fetoprotein levels have higher state anxiety than women undergoing testing because of advanced maternal age, but that indication is much less a factor than are partner differences. Therefore, increased anxiety after abnormal maternal serum alpha-fetoprotein testing results cannot be reasonably used as an argument against such testing.

Early genetic amniocentesis and chorionic villus sampling. Expanding the opportunities for early prenatal diagnosis.

At centers where chorionic villus sampling (CVS) programs are operational, first-trimester prenatal diagnosis has been shown to have many advantages, both medical and psychologic. However, most medical centers do not have CVS capability, nor are all patients candidates for CVS. We investigated the feasibility of performing very early genetic amniocentesis (9-13 weeks' gestational age). The results from those amniocenteses were compared to our own CVS data. In experienced hands, (1) CVS can be performed safely at 8-13 weeks, with the most technical ease at 9-11 weeks; (2) CVS or amniocentesis can be performed on many patients at 12-13 weeks or perhaps even earlier, although no accurate loss rates are available yet; (3) when technically feasible, CVS may be advantageous because of the much faster time period for cytogenetic results from direct preparation or short-term culture; and (4) in those patients on whom CVS cannot be performed, early amniocentesis in selected patients may offer the benefits of early diagnosis.

Selective first-trimester termination in octuplet and quadruplet pregnancies: clinical and ethical issues.

The induction of grand multiple gestations is a known complication of infertility treatments. The obstetric outcome in such cases has been very poor. We have evaluated, counseled, and performed first-trimester selective terminations for four patients, all treated with human menopausal gonadotropin, one with octuplets and three with quadruplets. In all cases, the gestations were reduced to twins. In two of the four cases, the pregnancy continued to near term without problem and resulted in the delivery of healthy twins. In the third case, pregnancy continued without problems for eight weeks, at which time renal agenesis was identified in one of the twins. In the fourth case, preterm labor five weeks later could not be stopped. Significant ethical issues must be addressed. We argue that selective termination in appropriate circumstances (eg, when the ability to carry the pregnancy to viability is very small) is ethically justified because it meets the criterion of least harm and most potential good.