R Murru

Association between different morphological types and abnormal karyotypes in early pregnancy loss

To identify the abnormal transvaginal ultrasound (TVS) findings typical of aneuploidic pregnancies that end with early pregnancy loss (EPL).

Interstitial deletion at 11q14.2-11q22.1 may cause severe learning difficulties, mental retardation and mild heart defects in 13-year old male

Interstitial deletions of the long arm of chromosome 11 are rare, and they could be assumed as non-recurrent chromosomal rearrangements due to high variability of the size and the breakpoints of the deleted region. The exact region of the deletion was difficult to be determined before the use of molecular cytogenetic techniques such as array comparative genomic hybridization (aCGH). Here, a 13-year old boy with severe learning difficulties, mental retardation and mild heart defects is described. Conventional G-band karyotyping was performed and it is found that the patient is a carrier of a de novo interstitial deletion on the long arm of chromosome 11, involving 11q14 and 11q22 breakpoints. Further investigation, using aCGH, specified the deleted region to 11q14.2-11q22.1. There was a difficulty in correlating the genotype with the phenotype of the patient due to lack of similar cases in literature. More studies should be done in order to understand the genetic background that underlies the phenotypic differences observed in similar cases.

Prenatal diagnosis of proximal partial trisomy 1q confirmed by comparative genomic hybridization array: molecular cytogenetic analysis, fetal pathology and review of the literature

BACKGROUND Partial trisomy of the long arm of chromosome 1 (1q) is an exceptionally rare chromosomal abnormality and most of the prenatally diagnosed cases are associated with either complete (q11-qter) or large (q21-qter) duplications with pre- or perinatal demise of all reported cases. The most common sonographic findings associated with this karyotype abnormality include ventriculomegaly, increased nuchal translucency or nuchal fold, renal and cardiac abnormalities, craniofacial dysmorphism, and limb deformities. However, there is a wide spectrum of clinical manifestations due to the great variability in the extent of the duplication size and the possible contribution of additional genetic rearrangements in the final phenotype. CASE REPORT We report on a female fetus with sole partial trisomy 1q presenting with multiple structural malformations in the second trimester scan. Standard karyotyping demonstrated a large duplication on the proximal end of chromosome 1 [46,XX,dup(1)(pter→q31::q31→q12::q31→qter)] and further application of comparative genomic hybridization array confirmed the diagnosis and offered a precise characterization of the genetic defect. CONCLUSION A fetus with nonmosaic partial trisomy 1q that was prenatally diagnosed upon multiple abnormal ultrasound findings is presented. A detailed review of the currently available literature on the prenatal diagnostic approach of partial trisomy 1q in terms of fetal sonographic assessment and molecular cytogenetic investigation is also provided. The use of novel molecular techniques such comparative genomic hybridization array could shed further light on the correlation between the genes identified in the chromosomal region of interest and the resultant phenotype.

P09.14: Dilated lateral ventricles and micrognathia by ultrasound examination in fetus with mosaic trisomy 9

diagnosed prenatally. Pregnant aged 32 years old, the couple are cousins, and they had other 2 healthy children. It was the first time that went to the urgencies of our hospital; the gestational age was 34+6 weeks and she had spontaneous amniorrhexis four hours before. The following echographics findings are observed: agreed fetus with amenorrhoea, polyhydramnios with very dense amniotic fluid that produces level by its deposit in parts declivities, fetus in attitude of flexion with little mobility, very ecogenic fetal tegument, of redundant aspect mainly at level of back and members. Depressed nasal bridge. Other malformations were not seen and congenital icthyosis was suspected. 12 hours later, a woman of 2800 gr of weight was born by caesarean section, without external or internal malformations, except for a generalized hyperkeratosis distributed in plates. After the birth a progressive fall of the hyperkeratosic plates took place, being heavy, rough and dry skin. At the moment, the baby counts 2 months of age and she is well, being pending some specific studies (hystopatologics and ultrastructural studies of the skin). The prenatal and postnatal images are contributed.

P09.19: Fetal loss and complications after genetic amniocentesis

Objectives: To evaluate the rate of preterm delivery (PTD) following late amniocentesis (>24 weeks of gestation). Methods: A retrospective cohort of all women with singleton pregnancy who underwent late amniocentesis in one tertiary center between 2005–2009, due to various indications, excluding cases of suspected amnionitis or premature rupture of membranes. Results: The initial cohort included 182 women. Pregnancy outcome was validated in 158 women who underwent amniocentesis at 24–36 weeks of gestation (mean, 31.4 ± 1.9). 13 women were excluded due to premature labor induction or cesarean section for suspected IUGR. Indications for late amniocentesis included abnormal ultrasonographic findings (n = 98), suspected intrauterine CMV or toxoplasmosis infection (n = 19), maternal age (n = 13), abnormal first or second trimester biochemical markers (n = 8) and others (n = 7). The rate of spontaneous PTD (<37 weeks) was 8.9% (13/145), mean gestational age at delivery 34.7 ± 1.3 (32–36 weeks). In only 5 (3.4%) delivery occurred ≤34 weeks of gestation. In one case (0.68%) of amniocentesis performed at 32 weeks of gestation, delivery occurred within 48 hours. In 4 cases (2.75%) delivery occurred within 10 day. The rate of PTD and mean gestational age at delivery stratified by grouped gestational age at amniocentesis is presented at Table 1. If cases of amniocentesis performed for ultrasonographic findings to rule out chromosomal abnormalities (n = 117/182), abnormal karyotype was found in 3 cases (2.56%). Conclusions: The risk of significant prematurity following late amniocentesis is low.

P15.14: Absence of ultrasound abnormalities in a fetus with a small supernumerary marker chromosome (sSMC) found at prenatal diagnosis

Human small supernumerary marker chromosomes (sSMC) are present in 0.043% of newborn infants. They can be defined as additional centric chromosome fragments and generally are equal in size or smaller than a chromosome 20 of the same metaphase spread. Prenatal diagnosis of supernumerary marker chromosomes (SMC) is problematic because of the difficulty of predicting the phenotype. The assessment of phenotypic risk is based on the size, morphology and origin of the SMC. We found a sSMC in long term culture of chorionic villi performed for increased nuchal translucency in a 38 year old woman at 12+4 weeks gestation. Amniocentesis was performed at 15+5 weeks: GTGbanding analysis of amniotic cells confirmed the presence of the additional marker chromosome (karyotype:47,XX,+mar). Both parents had normal karyotypes. Fluorescence in situ hybridization (FISH) analysis using chromosomal specific alphoid satellite DNA probes and whole chromosome paint probes showed that the extra sSMC was derived from chromosome 14. Further characterization of SMC performed by centromere-near-specific multicolor FISH (subcenM-FISH) showed it was an inv dup(14)(q11.1). This region consist of heterochromatic material: SMC without euchromatic content are more likely to result in normal phenotypes. Maternal uniparental disomy for chromosome 14 (associated with precocious puberty, short stature and highly variable developmental delay) was excluded by microsatellite analysis. Pregnancy was continued. No morphological abnormalities were observed on any ultrasound examinations performed during pregnancy. No dysmorphic features were noticed at birth. At 1 year follow-up, the child was growing and developing normally. This case illustrates how a combination of ultrasound examination, FISH characterization and molecular analyses may enhance the accuracy of the information given (diagnosis and prognosis, risk estimates) during prenatal counseling.

P16.06: Nuchal translucency and other US markers in cases of trisomy 18

(n = 134). Over a total of 134 fetuses with increased NT, karyotype was analysed in 129 cases (96,3%) and pregnancy outcome was available in 124 cases (92.5%). A chromosomal anomaly was detected in 57 fetuses (44.2%). In 72 (55.8%) fetuses, the karyotype was normal. The overall incidence of an adverse pregnancy outcome in the latter subset was 25% (18/72). Anomalies were detected, at the time of ultrasound, in 12 cases (16%) with 4 isolated cardiac defects and 8 other structural defects. Genetic syndromes occurred in 5 (6.9%) fetuses with normal karyotype. An adverse neonatal outcome was recorded in 1 case in which there were normal findings at the 20-week scan. Conclusion: After exclusion of chromosomal anomalies, 18/72 of the fetuses with increased NT had an adverse pregnancy outcome diagnosed in utero in 17/72 cases. Counselling should stress that, if the karyotype is normal and no fetal structural malformations were missed prenatally, a favourable outcome can be expected.

P26.21: Multiple congenital anomalies syndrome with urorectal septum malformation, absent radii, cerebellar vermis aplasia: case report

routine ultrasound. A bilateral renal disease with oligohydramnios was diagnosed in her first pregnancy and the baby was stillborn with Potter sequence. In the actual pregnancy the ultrasound done at 26 + 4 weeks of gestation showed right pyelocalicial and proximal ureteral dilatation with narrowing. In the neonatal period a 3D scan with multiplanar views demonstrated a megaureter associated with ureteral valve and a distal ureteral stenosis. The diagnosis was confirmed via surgical exploration and histology. While rare this might be a cause of ureteral obstruction with progressive upper tract dilatation. We emphasize the value of multiplanar 3D which allowed a diagnosis that only few years ago was privative of excretory urography.

P01.39: Experience on 1,282 cases of genetic amniocentesis: fetal loss and complications

Objective: The purpose of this study was to measure the fetal nasal bone between 11–14 weeks of gestation in order to elaborate a reference range for the Brazilian population. Methods: In this prospective and transversal study, crown-rump length, nuchal translucency, and nasal bone length were measured in 171 singleton pregnancies between 11 and 14 weeks of pregnancy. For statistical analysis the linear regression was used. Results: 171 singleton pregnancies which newborns had a normal phenotype were included in this study. A reference range of fetal nasal bone was elaborated. Median and percentiles 5 and 95 were also determined. The reference range was done after adjusting the coefficient of determination (R2) was 59.4% (p < 0.001). Conclusion: The length of the nasal bone showed a linear growth between 11–14 weeks of gestation.

P10.30: Low risk of fetal loss and complications following genetic amniocentesis: experience on 942 cases

Objective: To assess the visualization of fetal nasal bones in second trimester fetuses using antenatal 3D US and post-mortem CT and compare with standard 2D US. Methods: 4 fetuses with Down syndrome and absent nasal bone on 2D US and 6 fetuses with non-facial malformations were included in the study. In addition prenatal 3D US with maximal mode rendering was performed antenatally and compared with images of the bony face acquired from multidetector CT-scan and 3D volume rendering after pregnancy termination. Results: The 6 fetuses with normal chromosomes had on both 3D US and 3D CT bilateral NB. Three fetuses with Down syndrome had in both methods absent NB. One fetus with Down syndrome had one right absent nasal bone and a hypoplastic left nasal bone. This interesting finding was not recognized in 2D US, suspected in 3D US and confirmed in CT. Conclusions: 2D US gives limited information in suspected hypoplastic or absent NB. 3D US with maximal rendering is a reliable tool in assessing both right and left NB prenatally. Postmortem 3D CT is an impressive tool in confirming 3D prenatal rendering of skeletal findings.