Laila Rhee-Morris

Mutations in the gene encoding c-Abl-binding protein SH3BP2 cause cherubism

Cherubism (MIM 118400) is an autosomal dominant inherited syndrome characterized by excessive bone degradation of the upper and lower jaws followed by development of fibrous tissue masses, which causes a characteristic facial swelling. Here we describe seven mutations in the SH3-binding protein SH3BP2 (MIM 602104) on chromosome 4p16.3 that cause cherubism.

Periaxin mutations cause recessive Dejerine-Sottas neuropathy.

The periaxin gene (PRX) encodes two PDZ-domain proteins, L- and S-periaxin, that are required for maintenance of peripheral nerve myelin. Prx(-/-) mice develop a severe demyelinating peripheral neuropathy, despite apparently normal initial formation of myelin sheaths. We hypothesized that mutations in PRX could cause human peripheral myelinopathies. In accordance with this, we identified three unrelated Dejerine-Sottas neuropathy patients with recessive PRX mutations-two with compound heterozygous nonsense and frameshift mutations, and one with a homozygous frameshift mutation. We mapped PRX to 19q13.13-13.2, a region recently associated with a severe autosomal recessive demyelinating neuropathy in a Lebanese family (Delague et al. 2000) and syntenic to the location of Prx on murine chromosome 7 (Gillespie et al. 1997).

Potential Pitfalls and Methods of Improving In Utero Diagnosis of Transposition of the Great Arteries, Including the Baby Bird’s Beak Image

The goal of this study was to analyze our recent experience with fetuses with transposition of the great arteries (TGA) to identify potential pitfalls and possible methods to better detect conotruncal anomalies such as TGA.

Comparison of single versus multiple echogenic foci in the fetal heart regarding risk of aneuploidy.

Objective. The purpose of this study was to investigate whether multiple echogenic cardiac foci (ECF) are associated with an increased risk of fetal trisomy 21 in our patient population. Methods. During a span of 38 months, all women found to have an ECF on obstetric sonography were identified as study patients and grouped into single‐ and multiple‐ECF groups. Age‐ and race‐matched patients were identified as a control group. Fetal anatomic sonographic examinations were assessed for other markers of aneuploidy and major abnormalities. The baseline risk for trisomy 21 was assessed by maternal serum screening or age alone if no serum screening had been performed. Trisomy 21 was assessed by amniocentesis or clinically at birth. Both univariate and multivariate analyses were used to assess for associations with trisomy 21. Results. Six of 71 patients (8.5%) with multiple ECF and 1 of 171 patients (0.6%) with a single ECF had trisomy 21. One of 242 control patients (0.4%) had trisomy 21. Logistic regression found multiple ECF (P < .008), the presence of a major finding or multiple minor findings (P = .0012), and a baseline risk for trisomy 21 of greater than 1 in 100 (P = .003) as independent associations with trisomy 21. Conclusions. Our results suggest that finding multiple ECF is a stronger predictor of trisomy 21 than what is described for a single ECF.

Prenatal Diagnosis of Omphalocele and Left Atrial Isomerism (Polysplenia) Including Complex Congenital Heart Disease With Ventricular Noncompaction Cardiomyopathy

We report prenatal diagnosis of a rare constellation of findings, including omphalocele and polysplenia (left atrial isomerism [LAI]) with cardiac malformations including ventricular noncompaction (VNC) cardiomyopathy. The heterotaxy syndromes (polysplenia or LAI and asplenia or right atrial isomerism) are rare syndromes in which organs that are usually asymmetric are abnormally symmetric or abnormally positioned. Complex congenital heart disease is frequently associated with heterotaxy, with the heart being substantially affected in both structure and orientation. Heterotaxy has also been occasionally associated with a rare type of cardiomyopathy: VNC, described by Feldt et al and Ozkutlu et al. Omphalocele is a relatively common birth defect that is due to failure of the abdominal wall to close in association with return of the bowel in the first trimester. We report a case in which all of these findings were present. The cardiac findings were previously included in a pathology series on LAI with VNC by Friedberg et al; however, to our knowledge, pre-natal diagnosis of this unique collection of findings has not been reported previously.

A Priori Attitudes Predict Amniocentesis Uptake in Women of Advanced Maternal Age: A Pilot Study.

Amniocentesis is an invasive procedure performed during pregnancy to determine, among other things, whether the fetus has Down syndrome. It is often preceded by screening, which gives a probabilistic risk assessment. Thus, ample information is conveyed to women with the goal to inform their decisions. This study examined the factors that predict amniocentesis uptake among pregnant women of advanced maternal age (older than 35 years old at the time of childbirth). Participants filled out a questionnaire regarding risk estimates, demographics, and attitudes on screening and pregnancy termination before their first genetic counseling appointment and were followed up to 24 weeks of gestation. Findings show that womens decisions are not always informed by screening results or having a medical indication. Psychological factors measured at the beginning of pregnancy: amniocentesis risk tolerance, pregnancy termination tolerance, and age risk perception affected amniocentesis uptake. Although most women thought that screening for Down syndrome risk would inform their decision, they later stated other reasons for screening, such as preparing for the possibility of a child with special needs. Findings suggest that womens decisions regarding amniocentesis are driven not only by medical factors, but also by a priori attitudes. The authors believe that these should be addressed in the dialogue on womens informed use of prenatal tests.

Fetal Gallbladder Duplication

A 29-year-old woman, gravida 2, para 1001, was seen for a new pregnancy. Her history was notable for a pregnancy 2 years earlier with preeclampsia (high blood pressure and proteinuria) at 38 weeks. She had no other health issues. For the current pregnancy, she underwent a sonographic nuchal translucency study at 12 weeks 5 days as well as full integrated maternal serum screening, both having negative results with a final trisomy 21 risk of 1 per 20,000 and trisomy 18 risk of less than 1 per 100,000. At an estimated menstrual age of 20 weeks, a fetal sonographic anatomic survey was performed, with the only positive finding being parallel double tubular structures with anterior blind endings positioned under the lower aspect of the liver, extending in the anteroposterior plane (Figure 1A). The appearance and location corresponded to the usual fetal gallbladder, but in this case there were 2. The first diagnostic possibility was gallbladder duplication. Other possibilities for an extracystic structure in the right upper quadrant of the abdomen were also considered, such as a choledocal cyst, a mesenteric cyst, and gastrointestinal duplication. Vascular malformations and a persistent right umbilical vein were excluded because of a lack of detectable blood flow. Follow-up sonographic examinations at estimated menstrual ages of 22 and 30 weeks (Figure 1B) revealed similar findings. A healthy male neonate was delivered vaginally at term with weight of 4115 g and Apgar scores of 8 and 8 at 1 and 5 minutes, respectively. On the basis of the obstetric sonographic findings and in the first days of life, the neonate had a sonographic examination (not shown), which again showed 2 tubular structures under the liver. This finding was reported with a differential diagnosis of a choledocal cyst versus a duplicated gallbladder. The first possibility was considered because it is more common and because a separate common bile duct was not identified. Because of these consideraClinical Letters

Increased false positive Down syndrome screening in women with sickle cell anemia.

This study seeks to determine whether there is a higher rate of false positive serum screening for Down syndrome in women with sickle cell anemia and, if so, which markers contribute to the false positive screen.