The evolution of genetic counseling at Johns Hopkins Hospital and beyond.

In celebration of the 100th birthday of Dr. Victor A. McKusick, we look back at the history of genetic counseling at Johns Hopkins Hospital and at some milestones for the profession. With the first students graduating from the Human Genetics program at Sarah Lawrence College in 1971, the genetic counseling profession is celebrating its 50th anniversary this year. The profession has seen growth in numbers and scope of practice, the evolution of a national society, the advent of certification and accreditation, the proliferation of graduate programs, the pursuit of state licensure, and collaboration with fellow genetics professionals. Many of the early jobs were at academic centers, such as Johns Hopkins Hospital, while today counselors are employed in a multitude of settings and engaged in a variety of roles.

First trimester diagnosis of holoprosencephaly secondary to a ring chromosome 7.

Holoprosencephaly (HPE) is a developmental defect in humans in which the forebrain fails to completely separate into two hemispheres. We describe a 12 3/7-week-old fetus found on ultrasound evaluation to have features consistent with HPE, including a single anterior ventricle, fused thalami, and a flattened profile. Cytogenetic analysis of chorionic villi revealed a ring chromosome 7 [r(7)]. This uncommon finding has been associated with growth delay, microcephaly, and dermatologic abnormalities. However, both the clinical features and the extent of cytogenetic imbalance of chromosome 7 are variable, and few reported cases of r(7) have been molecularly studied. To our knowledge, this is the first report of a prenatally identified r(7), molecularly characterized using array comparative genomic hybridization.

Clinical consequences of an increasing trend of preferential use of cultured villi for molecular diagnosis by CVS.

OBJECTIVE: To compare the use of uncultured versus cultured villus cells for DNA-based prenatal diagnosis. METHODS: A retrospective review of molecular testing of chorionic villus sampling (CVS) cases from 1988-2007. Method of analysis, gestational age (GA) at CVS and at diagnosis, time from procedure to results, results of maternal contamination studies, and the laboratory employed were abstracted from patient charts. Trends in laboratory practices over time were analyzed. RESULTS: Time from CVS to diagnosis was longer when cultured cells were used. Average GA at diagnosis was 14-6/7 weeks with cultured cells vs 13-0/7 weeks with uncultured villi (p < 0.001). Recently, laboratories are more frequently requiring cultured cells, resulting in significantly greater delays in time to diagnosis and GA at results. CONCLUSIONS: 'Direct' DNA extraction saves 2 weeks from CVS to results. More women are afforded the option of an earlier, safer pregnancy termination if uncultured villi are used for molecular diagnosis. Implementation of standardized DNA extraction protocols and sample-size requirements can optimize the use of uncultured villi for molecular prenatal diagnosis. Increased awareness of the importance of rapid results and the advantages of 'direct' DNA extraction from uncultured villi can lead to improvements that are of clinical significance for patients undergoing early prenatal diagnosis.

Prenatal detection of an interstitial deletion in 4p15 in a fetus with an increased nuchal skin fold measurement.

OBJECTIVES: The detection of an increased nuchal translucency (NT) or nuchal fold (NF) measurement is associated with an increased risk of common aneuploidies. Only rarely is it associated with other types of chromosome abnormalities. We report the prenatal finding of an increased NF in a fetus with an interstitial 4p deletion. METHODS: Standard karyotype analysis was followed by FISH with research generated BAC probes to precisely map the 4p deletion. RESULTS: The karyotype of the fetus was determined to be 46,XX,del(4)(p15.2p16.1) by G-banding analysis and was refined to 46,XX,del(4) (p15.1p15.32) after FISH analysis. The breakpoints were narrowed to 150 kb regions on each side. The deletion is approximately 14.5 Mb, containing approximately 47 genes. CONCLUSIONS: We report a case of an increased NF measurement associated with a 4p deletion. A literature review revealed a previous case of a 4p deletion in a fetus with an increased NT. Since chromosome deletions are rarely associated with an increased NT or NF, we believe it is significant that a 4p deletion has now been found in two unrelated cases. We mapped the deletion with BAC probes, generating a list of possible candidate genes involved in the pathogenesis of increased nuchal skin folds.