The Recurrent t(11;22)(q23;q11.2) Can Occur as a Post-Zygotic Event.

The AT-rich repeat on chromosome 22q11.2 is known to be involved in the recurrent constitutional t(11;22)(q23;q11.2).

The benefits and limitations of cell-free DNA screening for 22q11.2 deletion syndrome.

Cell-free DNA testing is increasingly being used to screen pregnant women for fetal aneuploidy. This technology may also identify microdeletion syndromes, including 22q11.2 deletion syndrome, the most common microdeletion syndrome, and the 22q11.

Cell-free DNA screening and sex chromosome aneuploidies.

Cell-free DNA (cfDNA) testing is increasingly being used to screen pregnant women for fetal aneuploidies. This technology may also identify fetal sex and can be used to screen for sex chromosome aneuploidies (SCAs). Physicians offering this screening will need to be prepared to offer comprehensive prenatal counseling about these disorders to an increasing number of patients.

Beare-Stevenson syndrome: two new patients, including a novel finding of tracheal cartilaginous sleeve.

Beare-Stevenson syndrome (BSS) is a rare FGFR2-associated craniosynostosis syndrome with a higher rate of sudden unexplained death than related conditions such as Apert, Pfeiffer, and Crouzon syndromes. BSS presents with craniosynostosis, cutis gyrata, and significant developmental delay in most patients who survive infancy. There have only been 21 reported patients with BSS, which limits prognostication for clinicians and likely does not capture the full extent of the phenotype.

CCBE1 mutation in two siblings, one manifesting lymphedema-cholestasis syndrome, and the other, fetal hydrops.

Background: Lymphedema-cholestasis syndrome (LCS; Aagenaes syndrome) is a rare autosomal recessive disorder, characterized by 1) neonatal intrahepatic cholestasis, often lessening and becoming intermittent with age, and 2) severe chronic lymphedema, mainly lower limb. LCS was originally described in a Norwegian kindred in which a locus, LCS1, was mapped to a 6.6cM region on chromosome 15.

Is it time to sound an alarm about false-positive cell-free DNA testing for fetal aneuploidy?

Testing cell-free DNA (cfDNA) in maternal blood samples has been shown to have very high sensitivity for the detection of fetal aneuploidy with very low false-positive results in high-risk patients who undergo invasive prenatal diagnosis. Recent observation in clinical practice of several cases of positive cfDNA tests for trisomy 18 and trisomy 13, which were not confirmed by cytogenetic testing of the pregnancy, may reflect a limitation of the positive predictive value of this quantitative testing, particularly when it is used to detect rare aneuploidies. Analysis of a larger number of false-positive cases is needed to evaluate whether these observations reflect the positive predictive value that should be expected.

Genetic screening in reproductive health care.

Genetic screening is used to identify individuals who have genetic variations or mutations that are associated with a particular disorder. Genetic screening may be useful to plan for periodic evaluation, implementation of preventive strategies, or initiation of therapeutic interventions. Current practice is to offer carrier screening for certain genetic diseases during the preconception encounter or more commonly as part of early prenatal care.

Incorporating first-trimester Down syndrome studies into prenatal screening: executive summary of the National Institute of Child Health and Human Development workshop.

The National Institute of Child Health and Human Development (NICHD), the Society for Maternal-Fetal Medicine, and the American College of Obstetricians and Gynecologists (ACOG), cosponsored a workshop on December 16-17, 2004, to discuss the evidence for first-trimester Down syndrome screening and to explore the effects of combining first- and second-trimester screening, given the results of recent U.S. trials.

Impact of self-reported familiarity with guidelines for cystic fibrosis carrier screening.

Objective: To assess the impact of self-reported familiarity with published guidelines on knowledge, implementation, and opinions of obstetrician-gynecologists regarding carrier screening for cystic fibrosis.

Methods: A questionnaire pertaining to cystic fibrosis screening guidelines was mailed to 1,165 members of the American College of Obstetricians and Gynecologists.

Results: Sixty-four percent of questionnaires were returned.

Practice patterns of obstetrician-gynecologists regarding preconception and prenatal screening for cystic fibrosis.

Objective: To assess practices of obstetrician-gynecologists regarding carrier screening for cystic fibrosis (CF).

Methods: A questionnaire investigating practice patterns and opinions pertaining to CF screening was mailed to 1165 members of the American College of Obstetricians and Gynecologists (ACOG), of whom 565 participate in the Collaborative Ambulatory Research Network (CARN) and 600 were randomly selected.

Results: Of the questionnaires, 64% were returned.

Screening for aneuploidy in twin pregnancies: maternal age- and race-specific risk assessment between 9-14 weeks.

The aim of this study was to calculate the risk for aneuploidy in twin pregnancies between 9-14 weeks utilizing maternal age, race and dizygotic twinning rates. Using previously published risks for aneuploidy in singletons and twins at the time of amniocentesis and at term, we calculated new risk estimates for twins at 9-14 weeks gestation or at the time of chorionic villus sampling. Using these tables, the risk for trisomy 21 in at least one fetus of a twin gestation in a 32-year-old at 9-14 weeks is 1/285 for Whites and for African-Americans.

Omodysplasia: an affected mother and son.

We describe a second family with mother to son transmission of omodysplasia, a rare skeletal dysplasia characterized by shortened humeri, shortened first metacarpals and craniofacial dysmorphism. The mother in this family had been diagnosed previously with Robinow syndrome; subsequently, her diagnosis was reclassified. Her pregnancy was closely monitored antenatally with serial ultrasound examinations.