Debra Day-Salvatore

GPC3 mutation analysis in a spectrum of patients with overgrowth expands the phenotype of Simpson-Golabi-Behmel syndrome.

Simpson-Golabi-Behmel syndrome (SGBS) is an X-linked overgrowth syndrome caused by deletions in glypican 3 (GPC3). SGBS is characterized by pre- and postnatal overgrowth, a characteristic facial appearance, and a spectrum of congenital malformations which overlaps that of other overgrowth syndromes. We performed GPC3 deletion screening on 80 male patients with somatic overgrowth in the following categories: SGBS (n = 19), possible SGBS (n = 26), including families in which individuals had previously been diagnosed with other overgrowth syndromes, and Wiedemann-Beckwith syndrome (WBS) (n = 35). Using exon-specific PCR and Southern blot analysis, we identified seven GPC3 deletions. In most cases a clear X-linked family history was not present. In two cases, GPC3 deletions were identified in patients belonging to pedigrees published previously as other overgrowth syndromes: one with a diagnosis of Sotos syndrome and the other Perlman syndrome with nephroblastomatosis. A third patient developed hepatoblastoma, a tumor type not previously described in SGBS. No GPC3 deletions were identified among the WBS patients. Direct sequencing of all GPC3 exons in the remaining 13 SGBS patients without GPC3 deletions did not identify any further mutations, raising the possibility of alternative silencing mechanisms and/or other genes in the pathogenesis of SGBS. Our results validate the clinical specificity of the facial appearance, skeletal/hand anomalies, and supernumerary nipples in patients with GPC3 deletions. Our data also suggest that nephroblastomatosis and hepatoblastoma are included in the phenotypic spectrum of GPC3 deletions and SGBS, underscoring the importance of tumor surveillance in these children.

Prenatal Detection of Fetal Trisomy 18 Through Abnormal Sonographic Features

Objective. To describe the prenatal detection of fetal trisomy 18 through abnormal sonographic features and to determine the sensitivity of sonographically detecting fetuses with trisomy 18. Methods. All genetic and cytogenetic records of fetuses with trisomy 18 were reviewed retrospectively (1992‐2002). From these, singleton fetuses who had prenatal sonography at our unit were identified. The maximal numbers of individual abnormalities from 1 sonographic examination (not limited to type of organ system) were recorded. Each abnormality was classified as major, minor, or “other,” and each organ system was classified as abnormal only once, regardless of the number of individual abnormalities identified in that system. The sensitivity of sonography in detecting abnormalities of trisomy 18 was determined. Results. Of 38 fetuses identified with trisomy 18, all had 4 or more prenatally detected sonographic abnormalities (sensitivity of sonographic detection of fetuses with trisomy 18, 100%). The median number of abnormalities per examination was 8 (range, 4‐19). Sonographically detected major abnormalities were cardiac (84%; n = 32), central nervous system (87%; n = 33), gastrointestinal (26%; n = 10), and genitourinary (16%; n = 6). Sonographically detected minor abnormalities were short ear length below the 10th percentile for gestational age (96%; n = 26/27), upper extremities and hands (95%; n = 36), lower extremities and feet (63%; n = 24), and face (53%; n = 20). Fifty percent (19 of 38) had choroid plexus cysts identified, but this was never an isolated finding. Conclusions. In experienced hands, the sensitivity of detecting fetal trisomy 18 on prenatal sonography is 100%, and all cases will have multiple anomalies visualized.

The prenatal ultrasonographic visualization of imperforate anus in monoamniotic twins.

4023, 1994 16. Brock DJH: Prenatal diagnosis of cystic fibrosis. Ju Rodeck CH, Nicolaides KH (Eds): Prenatal Diagnosis. New York, John Wiley & Sons, 1985, p 159

Prenatal Sonographic Findings Associated With Nonmosaic Trisomy 9 and Literature Review

T risomy 9 was first reported in 1973 through blood lymphocyte testing in a newborn male with multiple congenital anomalies. 1 Since that time, only approximately 30 cases of mosaic or nonmosaic trisomy 9 have been reported 2 ; therefore, this is a relatively rare chromosomal abnormality, constituting only 2.7% of all trisomic cases. 3 Nonmosaic or complete trisomy 9 is a lethal diagnosis, with most fetuses dying prenatally or during the early postnatal period. Those who survive usually have mosaic trisomy 9 and have severe motor and mental deficiencies. With mosaic trisomy 9, the prevalence and severity of malformations and mental deficiency correlate with the percentages of trisomic cells in different tissues. 4 4 Because most complete trisomy 9 cases end in spontaneous abortion in the first trimester, there is a paucity of reports regarding the prenatal sonographic findings of complete trisomy 9. To our knowledge, only 7 cases of nonmosaic trisomy 9 that were specifically detected on prenatal sonography have been reported in the literature: first trimester (n = 2), second trimester (n = 2), and third trimester (n = 3). 3,5-9 There are distinct features associated with complete trisomy 9. Clinical and sonographic findings that have been described include intrauterine growth restriction, central nervous system abnormalities, cranial and facial anomalies, skeletal defects, congenital heart defects, and urogenital abnormalities. 6.8 8 The purpose of this report is to describe the prenatal sonographic findings in a second-trimester fetus with trisomy 9 and also to review the sonographic findings of all published cases of nonmosaic trisomy 9 that were specifically detected on sonography.

An economic evaluation of prenatal strategies for detection of trisomy 18

OBJECTIVE The objective of this study was to perform an economic evaluation of prenatal diagnostic strategies for women who are at increased risk for fetal trisomy 18 caused by either fetal choroid plexus cysts discovered in a conventional sonogram or an abnormal triple screen. STUDY DESIGN The prevalence of trisomy 18 in the presence of second-trimester fetal choroid plexus cysts and also in the presence of abnormal triple screen were made on the basis of previously reported studies. A cost/benefit analysis and cost-effectiveness determination of 3 strategies were performed: (1) no prenatal diagnostic workup of at-risk patients, (2) universal genetic amniocentesis of all at-risk patients, and (3) universal second-trimester targeted genetic ultrasonography of all at-risk patients with amniocentesis (for fetal karyotyping) reserved only for those with abnormal ultrasonography results. RESULTS The strategy of no prenatal diagnostic workup was the least expensive approach, costing

Economic Evaluation of Prenatal Carrier Screening for Fragile X Syndrome

1,650,000 annually in the United States. The more costly approach was the strategy of universal amniocentesis for detecting fetal trisomy 18 in the presence of either second-trimester choroid plexus cysts or abnormal maternal serum screening, generating an annual cost of approximately

Prenatal Detection of Fetal Aneuploidy by Sonographic Ear Length

12 million and 40 fetal losses as a result of amniocenteses. The strategy of targeted genetic ultrasonography generated an annual cost of only

Blepharophimosis, hypoplastic radius, hypoplastic left heart, telecanthus, hydronephrosis, fused metacarpals, and “prehensile” halluces: A new syndrome?

5 million and 8 fetal losses as a result of amniocenteses. CONCLUSIONS Routine second-trimester amniocentesis in patients at increased risk for fetal trisomy 18 caused by either the presence of fetal choroid plexus cysts or abnormal triple screening is not justified from the cost/benefit point of view.

Oculo-palatal-cerebral syndrome: a second case.

OBJECTIVE The objective of this study was to conduct an economic evaluation of routine prenatal carrier testing for fragile X syndrome. METHODS This economic analysis was conducted from the societal perspective. A cost-benefit equation was developed based on the premise that the cost of routinely offering prenatal carrier testing for fragile X syndrome should be at least equal to, or less than, the cost of the current practice of not offering such testing. Sensitivity analyses included key assumptions regarding therapeutic abortion rates (50-100%) and patient screening acceptance rates (50-80%). RESULTS A policy of routinely offering prenatal carrier testing for fragile X syndrome may be beneficial only if the cost per screening test is less than

Anticardiolipin antibodies in first- and second-trimester pregnancy loss

120 during the first year of the screening program, or less than