Rare interstitial deletion (2)(p11.2p13) in a child with pericentric inversion (2)(p11.2q13) of paternal origin.

An unbalanced 46,XY,der(2)del(2)(p11.2p13) inv(2)(p11.2q13) karyotype was found in a phenotypically abnormal child with a de novo interstitial deletion of band 2p12 associated with an inv(2)(p11.2q13) inherited from the father. The inv(2) is generally considered a benign familial variant without significant reproductive consequences. However, our findings led us to consider a previously proposed mechanism of unequal meiotic crossing over at the base of a parental inversion loop, which could lead to either a deletion or duplication of a segment adjacent to the inverted region in the offspring. This phenomenon has been reported in other inversions of chromosomes 1, 7, 13, 15, and 17 and may explain the origin of the deletion in our patient. Although repetitive sequences might be present around such inversions, which could predispose to de novo deletions independently of the inversion, current evidence including this case favors a proposed causal relationship between the parental inversion and the deletion in the child. Our review and results suggest there could be a small risk for a related imbalance to couples with an inv(2)(p11.2q13). For del(2)(p11.2p13), which is rare, a more distinct phenotype has been proposed herein. Our patient shared several findings with the three previously published cases, namely the broad nasal bridge, abnormal ears, high-arched palate, psychomotor retardation, and micrognathia. However, our patient also had sensorineural hearing loss and significant hypotonia, which have not been previously reported, thereby expanding our understanding of this rare deletion. Am. J. Med. Genet. 87:139-142, 1999. Published 1999 Wiley-Liss, Inc.

Prospective pilot evaluation of early (11-14 weeks' gestation) amniocentesis in 75 patients.

Prenatal diagnosis by amniocentesis has traditionally been accomplished at 15-18 weeks' gestation. Cytogenetic and biochemical results are usually available in 7-28 days, that is, by 16-22 weeks' gestation. Amniocentesis performed at 11-14 weeks facilitates earlier diagnosis, in some cases before 12 weeks' gestation. During the study period, 726 genetic amniocenteses were performed, 75 as part of the prospective early amniocentesis protocol. Of the 75 patients included in this pilot study, as well as the 75 patients in the control group, the success rate for obtaining an accurate cytogenetic diagnosis by early amniocentesis was 75/75 (100%) and the complication rate was 2/75 (2.6%: incidence of need for repeat amniocentesis, 1/75; uncorrected spontaneous abortion rate, 1/75). The indications for referral, population profile, mean gestational age at testing, and both the cytogenetic as well as obstetric outcomes are summarized in the report. This pilot study supports the hypothesis that amniocentesis at 11-14 weeks is efficacious when performed by experienced personnel and affords earlier counseling, testing, and availability of results compared to traditional amniocentesis.

Analysis of indications for referral to a multidisciplinary medical genetics clinic: implications for training programs in obstetrics and gynecology.

Clinical genetics has become an integral component of obstetric training. Advances in prenatal screening (particularly maternal serum alpha-fetoprotein) and the clinical applications of molecular technologies have broadened the indications for referral to geneticists. During the study period, 1237 patients were referred for genetics consultation. A total of 596 (48%) were referred because of cytogenetic indications (576 for genetic amniocentesis); 252 (20%) because of multifactorial-developmental abnormalities; 204 (17%) because of risk of diseases attributable to single-gene mutations; 58 (5%) because of antenatal teratogen exposure(s); and 127 (10%) because of other reasons. Herein we summarize our experience as a multidisciplinary genetics unit and offer recommendations for broadening resident training curricula to meet current clinical needs. These data will be useful for enhancement of health care use and more effective direction of limited resources.

Maternal serum alpha-fetoprotein (MSAFP) screening: the Keesler experience.

Maternal serum alpha-fetoprotein (MSAFP) screening is rapidly becoming a standard of practice in all regions of the United States and Canada. This paper will review the initial results of MSAFP screening in 761 patients at USAF Medical Center Keesler, and offer recommendations for Department of Defense hospitals offering such testing.

Gastroschisis and omphalocele: prenatal diagnosis and perinatal management.

Obstetric ultrasonography has made the prenatal diagnosis of gastroschisis and omphalocele more common. We present illustrative cases and review the ultrasonographic features. Because of the increased risk of concomitant abnormalities (including trisomies) with omphalocele, full evaluation is indicated when this diagnosis is suspected. Recent perinatal approaches to delivery have favoured caesarean section, without scientific evidence that outcome is improved. Our experience, as well as a review of the literature, suggests that the outcome for vaginally delivered infants is acceptable. A prospective study of this question is needed.