Prenatal diagnosis of trisomy 21 without the Down syndrome phenotype

OBJECTIVE: To report a patient with the prenatal diagnosis of trisomy 21 without the clinical Down syndrome (DS) phenotype secondary to the absence of the Down syndrome chromosomal region (DSCR) in a derivative chromosome 21. CASE REPORT AND METHODS: A newborn patient with prenatal diagnosis of duodenal atresia. Cytogenetic studies revealed a regular trisomy 21. At birth, she did not present the clinical features of DS. FISH analysis was performed in the patient with the LSI spectrum probe for the DSCR and in the mother with FISH multicolor analysis using painting probes for chromosomes 20 and 21. RESULTS: FISH analysis in the patient showed two hybridization signals suggesting that the third chromosome 21 did not have the DSCR region explaining the absence of the DS phenotype. FISH multicolor analysis in the mother showed three hybridization signals for chromosomes 20 and 21, concluding a maternal karyotype, 46,XX,t(20;21)(p11.2;q22.1). CONCLUSIONS: The patient was found to have a derivative chromosome 21 secondary to a nondisjunction error in meiosis II without the DS critical region and the phenotype was mostly secondary to the combination of the two partial trisomies.     

Prior fertility in the male partner does not predict a normal semen analysis

A history of male fertility is not an accurate predictor of a normal semen analysis result. The semen analysis should remain part of the evaluation of the infertile couple even in cases where a history of male fertility is reported.     

Association of microcephaly and cafe-au-lait spots in a patient with ring chromosome 12 syndrome

We describe a patient who was evaluated because of delayed development. The patient had microcephaly and cafe-au-lait spots and the facial features included upward slanting of the palpebral fissures, short nasal bridge and a highly arched palate. In addition the external ears had bilateral over folded helices, there was clinodactyly of the fourth and fifth fingers and multiple cafe-au-lait spots on the back, buttocks and thighs. Chromosomal analysis of peripheral blood showed 46,XY,-r(12)(p13.3q24.33)[73]/45,XY,-12[8]/47,XY,r(12)(p13.3q24.33),+r(12)(p13.3q24.33)[2]. This is the eighth case of a patient with a ring chromosome 12 to be reported so far. The similarity of our patient to those previously described suggests that the ring chromosome 12 syndrome can be delineated as a distinct entity with characteristic clinical features.     

Prenatal diagnosis and molecular cytogenetic characterization of a pure ring chromosome 21 with a 4.657-Mb 21q22.3 deletion

ObjectiveWe present diagnosis and molecular cytogenetic characterization of a pure ring chromosome [r(21)] with a 4.657-Mb 21q22.3 deletion.Case reportA 44-year-old woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype 46,XX,r(21)(p11.2q22.3). Prenatal ultrasound findings were unremarkable. Simultaneous array comparative genomic hybridization (aCGH) analysis on uncultured amniocytes revealed a 4.657-Mb deletion at 21q22.3. The parental karyotypes were normal. The pregnancy was subsequently terminated, and a malformed fetus was delivered with facial dysmorphism and clinodactyly. Postnatal cytogenetic analysis of umbilical cord revealed a karyotype of 46,XX,r(21)(p11.2q22.3). aCGH analysis of umbilical cord revealed the result of arr 21q22.3 (43,427,188–48,084,156) × 1.0 with a 4.657-Mb 21q22.3 deletion encompassing 57 Online Mendelian Inheritance in Man (OMIM) genes including TRPM2, TSPEAR, COL18A1, COL6A1, COL6A2, LSS, PCNT, DIP2A, S100B and PRMT2. Metaphase fluorescence in situ hybridization (FISH) analysis of the umbilical cord fibroblasts confirmed a 21q22.3 deletion.ConclusionPrenatal diagnosis of an r(21) should include molecular cytogenetic characterization such as aCGH and FISH to determine the extent of the 21q22.3 deletion.     

The utility assessment of Chinese pregnant women towards the birth of a baby with Down syndrome compared to a procedure-related miscarriage

OBJECTIVE: This study was performed to investigate the preferences of Chinese pregnant women for Down syndrome-affected birth compared to invasive test-related miscarriage, using the standard gamble approach, and to investigate whether there is a difference in Utility Score between general obstetric patients and those who request prenatal screening. METHODS: An interviewer-administered survey was conducted on 67 women who presented to the General Obstetric Clinic for booking visits and 69 women who presented to the first-trimester Combined Screening Clinic for fetal Down syndrome in a University Obstetric Unit. Preferences for Down syndrome-affected birth compared to invasive test-related miscarriage were assessed using the standard gamble approach. The differences in Utility Scores for the two outcomes and difference in scores between the two study groups were compared. RESULTS: There was no significant difference in any of the Utility Scores studied between the two study groups. Therefore the summary statistics were performed using the whole study population. The median Utility Score for a Down syndrome-birth was 0.20 (IQR: 0.10-0.40), which was significantly lower than that of 0.55 (IQR: 0.40-0.80) for a procedure-related miscarriage (p < 0.001). Also, the Utility Scores were neither found to be associated with any particular patient demographic characteristics nor their perception of the functional disability of individuals with Down syndrome. CONCLUSION: The Chinese pregnant women in Hong Kong consider a Down syndrome-affected birth as a much worse health state and life event than a miscarriage. Whether or not to have a screening test appeared to be a result of accessibility and affordability rather than fundamental differences in attitude towards Down syndrome. The findings of the study provide important information on how prenatal screening and diagnosis of fetal chromosomal abnormalities should be offered.     

Fetal facial sonographic markers for second trimester Down syndrome screening in a Thai population

Objective

To assess the efficacy of using facial sonographic markers for screening fetuses in the second trimester for Down syndrome (DS) in a high-risk Thai population.

Method

Frontomaxillary facial angle (FMF) and nasal bone length (NBL) were measured prospectively in pregnant women at high-risk for DS who were undergoing genetic amniocentesis from November 2008 to October 2009. The receiver operator characteristic (ROC) curves were constructed to assess the screening efficacy of FMF angle and NBL.

Result

A total of 460 pregnant women were recruited, and a mid-sagittal facial profile was obtained for 403 fetuses. There were 386 fetuses with normal chromosomes, 10 fetuses with DS, 1 fetus with trisomy 13, and 1 fetus with trisomy 18. The remaining 5 fetuses had balanced translocation (n = 2), deletion (n = 1), and mosaic Turner (n = 2). Two different combinations of FMF angle and biparietal diameter to nasal bone length (BPD:NBL) ratio for DS screening in the second trimester achieved 50% and 90% detection rates and 4.4% and 14.0% false positive rates, respectively.

Conclusion

The combination of FMF angle and BPD:NBL ratio has a high sensitivity and specificity for screening for DS in the second trimester in a high-risk Thai population.     

Follicular fluid antimullerian hormone (AMH) does not predict IVF outcomes in polycystic ovary syndrome patients

IntroductionAMH, is a member of the transforming growth factor (TGF-β) produced by granulosa cells with the highest expression being in small antral follicles. Our objective is to evaluate the predictive value of follicular AMH levels as an indicator of IVF outcomes in PCOS patients.Material and methodsA total of 63 patients undergoing the IVF trail were recruited for this prospective case-control study. The patients were classified into three groups: Group I: 43 patients with Polycystic ovary syndrome (PCOS). Group II: 20 normo-ovulatory patients were recruited for the IVF trail because of the male infertility factor (control group). Group III: consists of 33 patients from group I recruited to determine the effect of controlled ovarian hyperstimulation (COH) on serum AMH levels. Serum AMH levels were performed on day 3 of the menstrual cycle whereas the follicular fluid AMH level has been evaluated at the time of oocyte retrieval by enzyme linked immune-sorbent assay (AMH Gen II ELISA kit, Beckman Coulter, Inc. USA). AMH concentrations were adjusted to its protein content, to avoid possible bias due to FF volume variability. The relationship between follicular fluid AMH (FF AMH) levels and the number of oocytes retrieved, number of mature oocytes, number of embryos, fertilization and clinical pregnancy rate were assessed. The demographic data were similar between two groups as regards age and BMI.ResultsBoth serum AMH levels and FF AMH levels were significantly higher in PCOS patients than in the controls, the values for serum levels were (5.07 ± 3.39 ng/ml, 3.07 ± 2.09 ng/ml) respectively and for follicular fluid levels were (67 ± 50.7 ng/g¹, 38.5 ± 44.4 ng/g) respectively. Serum AMH levels showed a positive correlation with oocytes retrieved and mature oocyte number, but there was no significant correlation with good quality embryo number, fertilization rate or clinical pregnancy rate in PCOS patients. On the other hand FF AMH levels do not show correlation with any of the IVF outcomes mentioned above in PCOS patients. Interestingly, the interval change in serum AMH levels between baseline AMH levels and levels after COH had a significant predictive value of pregnancy.ConclusionsSerum AMH levels can predict the number of the retrieved oocytes and mature oocytes, whereas FF AMH may not be a valuable predictor for IVF outcomes in PCOS patients.     

Prenatal diagnosis and molecular cytogenetic characterization of a small supernumerary marker chromosome derived from chromosome 15 in a pregnancy associated with recurrent Down syndrome

ObjectiveWe present prenatal diagnosis and molecular cytogenetic characterization of a small supernumerary marker chromosome (sSMC) derived from chromosome 15 in a pregnancy associated with recurrent Down syndrome.Case reportA 33-year-old, gravida 4, para 2, woman underwent amniocentesis at 16 weeks of gestation because of a previous child with Down syndrome and a karyotype of 46,XY,der(14;21)(q10; q10),+21. In this pregnancy, amniocentesis revealed a karyotype of 47,XX,+21[12]/48,XX,+21,+mar[3]. The parental karyotypes were normal. The pregnancy was terminated, and a malformed fetus was delivered with characteristic craniofacial appearance of Down syndrome and hypoplastic middle phalanx of the fifth fingers. The placenta had a karyotype of 47,XX,+21[37]/48,XX,+21,+mar[3]. The umbilical cord had a karyotype of 47,XX,+21[38]/48,XX,+21,+mar[2]. In addition to trisomy 21, array comparative genomic hybridization (aCGH) on the DNA extracted from umbilical cord revealed 40～50% mosaicism for a 2.604-Mb duplication of 15q25.2–q25.3, or arr 15q25.2q25.3 (83,229,665–85,834,131) × 2.4 [GRCh37 (hg19)] encompassing 19 Online Mendelian Inheritance in Man (OMIM) genes. Quantitative fluorescent polymerase chain reaction (QF-PCR) using the DNAs extracted from cultured amniocytes and parental bloods revealed maternal origin of the sSMC(15) and the extra chromosome 21.Conclusion: aCGH is useful for identification of the nature of sSMC, and QF-PCR is useful for determination of the parental origin of the aberrant chromosomes.     

Duplication of chromosome 2 in association with ventriculomegaly - a case report.

This is a case report of the prenatal diagnosis of a de novo interstitial duplication of chromosome 2 (46,XX,dup(2)(p13p21) de novo) with an associated phenotypic abnormality. This chromosomal duplication is rare, only one has previously been described prenatally. Postnatal reports of similar duplications in this region have described associated dysmorphic features and significant neurodevelopmental delay. In our case, the only ultrasound finding was moderately severe ventriculomegaly. At post-mortem, ventriculomegaly was confirmed and there was associated macrocephaly (head circumference above the 97th centile) with no dysmorphic features seen.     

Mosaic ring chromosome 21, monosomy 21, and isodicentric ring chromosome 21: prenatal diagnosis, molecular cytogenetic characterization, and association with 2-Mb deletion of 21q21.1-q21.2 and 5-Mb deletion of 21q22.3

ObjectiveTo present the perinatal findings and molecular cytogenetic characterization of prenatally detected mosaic r(21).Materials, Methods, and ResultsA 29-year-old primigravid woman underwent amniocentesis at 22 weeks’ gestation because of hyperechogenic cardiac foci and intrauterine growth restriction. Amniocentesis revealed a karyotype of 46,XY,r(21)[15]/45,XY,–21[5]. The parental karyotypes were normal. The woman requested repeat amniocentesis. Oligonucleotide-based array comparative genomic hybridization was applied to the uncultured amniocytes, rapidly detecting a 2.09-Mb deletion of 21q21.1–q21.2 (21,495,262–23,580,815 bp) and a 5.03-Mb deletion of 21q22.3–q22.3 (41,887,412–46,914,715 bp). Cytogenetic analysis revealed a karyotype of 46,XY,r(21)[8]/45,XY,–21[3]/46,XY,idic r(21)[1]. The pregnancy was terminated, and a malformed fetus was delivered with clinodactyly, short big toes, separation between the first and second toes, prominent nasal bridge, downward slanting palpebral fissures, protuberant occiput, prominent forehead, broad anteverted nasal tip, long philtrum, thin upper lip, small mouth, and micrognathia. The placenta had a karyotype of 46,XY,r(21)[83]/45,XY,–21[11]/46,XY,idic r(21)[6], and the cord blood lymphocytes had a karyotype of 46,XY,r(21)[88]/45,XY,–21[9]/46,XY,idic r(21)[3]. Polymorphic DNA marker analysis determined a maternal origin for the deletion.ConclusionAn extra interstitial 21q deletion can be associated with mosaic r(21) in addition to a terminal 21q deletion. aCGH is useful in determining the breakpoints and associated subtle structural abnormalities in cases of prenatally detected ring chromosome in order to facilitate genetic counseling.     

Combining maternal age and serum alpha-fetoprotein to predict the risk of Down syndrome

Twenty-eight cases of Down syndrome with maternal serum alpha-fetoprotein (AFP) measured at second trimester were added to 137 previously reported cases. Seventy-eight percent of affected pregnancies had levels at or below the median AFP value, compared with 50% of unaffected pregnancies. Maternal age at delivery and serum AFP levels by multiples of the median were used to construct a table to determine the risk of Down syndrome. This was compared with the risk for a 35-year-old woman (one in 365). Similar risks were estimated for a 21-year-old with AFP below 0.4 multiples of the median, a 23-year-old below 0.5, a 26-year-old below 0.6, and a 29-year-old below 0.7 multiples of the median. This study provides guidelines for counseling pregnant women who have low serum AFP levels.     

Maternal heterodisomy/isodisomy and paternal supernumerary ring of chromosome 7 in a child with Silver-Russell syndrome

Silver-Russell syndrome (SRS) is clinically variable although most cases have several common signs. Different chromosomes and chromosomal regions have been associated with SRS. Maternal uniparental disomy (UPD) of chromosome 7 is responsible for 5-10% of cases, probably because of an imbalance between maternal and paternal imprinted genes and more recently maternal duplication or epimutations in the 11p15 imprinted region have been described. To date, only two patients with maternal UPD7 and a mosaic condition for a supernumerary ring 7 marker have been reported, and we here report a further case. Standard QFQ banding of lymphocytes as well as fluorescence in-situ hybridization analyses were performed to identify and characterize the supernumerary marker. UPD testing was performed on both the patient's and parents' DNA using chromosome 7 microsatellite markers. The patient demonstrated a ring in about 4% of the analysed cells. On the basis of cytogenetic and molecular results, break points were tentatively identified as 7p11.2 and 7q21. Maternal hetero-/iso-UPD and a paternal origin for the supernumerary ring were demonstrated. Clinical data comparison between our patient who has a SRS phenotype and cases with hetero-/iso-UPD7 mat and mosaicism for a paternally derived chromosome 7 ring and previously reported ring 7 cases suggest that the SRS phenotype is probably because of the UPD rather than to the partial trisomy.     

Hyaluronan binding assay does not predict pregnancy rates in IUI cycles in couples with unexplained infertility

Purpose

There are very few reports in the literature about the conservative surgical approach of large uterine myoma. The individualization of the surgery approach, the technical expertise and skill of the surgeon, the use of modern technologies/facilities could offer the optimal individualized treatment.

Methods

We performed a conservative combined surgical approach consisting of open laparoscopy myomectomy followed by laparotomy for the treatment of a very large uterine myoma of the anterior uterine wall in a 27-year-old non-pregnant woman with a history of progressive abdominal distension and symptoms related to abdomen pressure and constipation.

Results

The myoma weighted 12.010?kg. The postoperative course was good and 20?months after surgery, the patients had a successful pregnancy with a spontaneous delivery at the 39th week of a healthy baby weighting 3.260?kg.

Conclusions

In the case reported here, the careful pre-surgical evaluation, the technical expertise and skill of the surgeon, the choice of a combined approach with laparoscopy and open surgery and the use of modern surgical instruments have enabled us to achieve a significant result: the preservation of the anatomical integrity of the uterus and adnexa which allowed a successful natural pregnancy with spontaneous delivery.