Prenatal Chromosomal Diagnosis Research Articles

Prenatal diagnosis of mosaic ring chromosome 9

Prenatal DiagnosisVolume 26, Issue 9 p. 870-871 Letter to the Editor Prenatal diagnosis of mosaic ring chromosome 9 Chih-Ping Chen, Corresponding Author Chih-Ping Chen Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan Institute of Clinical Nursing, School of Nursing, National Yang-Ming University, Taipei, Taiwan College of Chinese Medicine, China Medical University, Taichung, TaiwanDepartment of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, TaiwanSearch for more papers by this authorChen-Li Lin, Chen-Li Lin Department of Obstetrics and Gynecology, Taipei City Hospital, Taipei, TaiwanSearch for more papers by this authorLi-Lu Chen, Li-Lu Chen Department of Obstetrics and Gynecology, Taipei City Hospital, Taipei, TaiwanSearch for more papers by this authorChen-Chi Lee, Chen-Chi Lee Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, TaiwanSearch for more papers by this authorWayseen Wang, Wayseen Wang Department of Medical Research, Mackay Memorial Hospital, Taipei, TaiwanSearch for more papers by this author Chih-Ping Chen, Corresponding Author Chih-Ping Chen Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan Institute of Clinical Nursing, School of Nursing, National Yang-Ming University, Taipei, Taiwan College of Chinese Medicine, China Medical University, Taichung, TaiwanDepartment of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, TaiwanSearch for more papers by this authorChen-Li Lin, Chen-Li Lin Department of Obstetrics and Gynecology, Taipei City Hospital, Taipei, TaiwanSearch for more papers by this authorLi-Lu Chen, Li-Lu Chen Department of Obstetrics and Gynecology, Taipei City Hospital, Taipei, TaiwanSearch for more papers by this authorChen-Chi Lee, Chen-Chi Lee Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, TaiwanSearch for more papers by this authorWayseen Wang, Wayseen Wang Department of Medical Research, Mackay Memorial Hospital, Taipei, TaiwanSearch for more papers by this author First published: 29 August 2006 https://doi.org/10.1002/pd.1515Citations: 9AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article.Citing Literature Volume26, Issue9September 2006Pages 870-871 RelatedInformation

Ring Chromosome 7 Presenting with Intrauterine Growth Restriction and Multiple Anomalies

Ring chromosome 7 is a very rare chromosomal anomaly that may have a grave prognosis. Nevertheless, the clinical features associated with ring chromosome 7 are highly variable. Here, we report a case with ring chromosome 7 and the perinatal findings. A 32-year-old, gravida 1, para 0, woman was referred to our hospital because of intrauterine growth restriction (IUGR) and oligohydramnios at 35 weeks of gestation. Prenatal ultrasound revealed a severe IUGR fetus presenting with multicystic kidney, hydronephrosis and oligohydramnios. At parturition, the birth weight of this male infant was 1,720 g, and a battery of anomalies were also noted, including imperforate anus, hypospadia, micropenis, right cryptorchidism, severe IUGR, multiple nevi on the forehead, shoulder and left thigh, brain atrophy, right multicystic kidney, and left mild hydronephrosis. Cytogenetic study from cord blood revealed a ring chromosome 7. Ring chromosome 7 is extremely rare and our case might be the 15 th and youngest case in the medical literature. Our case had multicystic kidney and imperforate anus, which have not been reported previously. Prenatal diagnosis of ring chromosome 7 is very difficult. When fetuses present with severe IUGR, oligohydramnios and multicystic kidney, chromosomal aberrations should be kept in mind, and perinatal cytogenetic workup is warranted.

Prenatal diagnosis of chromosome 4 mosaicism: Prognostic role of cytogenetic, molecular, and ultrasound/MRI characterization

Trisomy 4 mosaicism is extremely rare: herein we report the cytogenetic and molecular characterization and prenatal US findings of a case diagnosed prenatally. The diagnosis of level III mosaicism was established in cultured amniotic fluid cells (22.5%). At 22 weeks gestation, micrognathia and hypotelorism were suspected at 2-D sonography, and confirmed at 3-D examination. In addition, 2-D US showed cerebellar hypoplasia associated with borderline ventriculomegaly (confirmed at magnetic resonance imaging, MRI), spine deformity (hemivertebra), and a complete atrioventricular septal defect (AVSD). The pregnancy was terminated. Trisomy 4 mosaicism was confirmed in placental and fetal skin cultured cells. The cord blood karyotype was normal. Molecular analysis excluded uniparental disomy of chromosome 4, and indicated that the trisomy 4 was of maternal meiotic origin. In presence of chromosome 4 mosaicism, accurate fetal sonography and echocardiography are mandatory. Low level mosaicism and normal echographic examinations seem to be associated with good prognosis. In postnatal life, chromosome 4 mosaicism should be suspected, and cytogenetic analysis proposed of further tissues (i.e., skin), in presence of craniofacial dysmorphism, cardiac defects, and abnormal hands/feet, even if mental development is appropriate or only slightly impaired.

Prenatal diagnosis of ring chromosome 6 in a fetus with cerebellar hypoplasia and partial agenesis of corpus callosum: case report and review of the literature

Ring chromosome 6 (RC6) is a rare constitutional abnormality, with variable material loss, leading to a variable clinical phenotype: minimal physical anomalies and mild psychomotor retardation to severe physical and mental defects. Among the 22 published cases, only five have been prenatally detected. We describe here a RC6 prenatally diagnosed. Ultrasound follow-up showed growth retardation and cerebellar hypoplasia. Magnetic resonance imaging (MRI) confirmed this, but showed a partial corpus callosum agenesis, leading to amniocentesis and revealing the chromosomal abnormality. Imaging features were correlated with autopsy findings.

Prenatal diagnosis of ring chromosome 6 in a fetus with cerebellar hypoplasia and partial agenesis of corpus callosum: case report and review of the literature

Ring chromosome 6 (RC6) is a rare constitutional abnormality, with variable material loss, leading to a variable clinical phenotype: minimal physical anomalies and mild psychomotor retardation to severe physical and mental defects. Among the 22 published cases, only five have been prenatally detected. We describe here a RC6 prenatally diagnosed. Ultrasound follow-up showed growth retardation and cerebellar hypoplasia. Magnetic resonance imaging (MRI) confirmed this, but showed a partial corpus callosum agenesis, leading to amniocentesis and revealing the chromosomal abnormality. Imaging features were correlated with autopsy findings.

Factors influencing parental decision making in prenatal diagnosis of sex chromosome aneuploidy.

To evaluate factors influencing parental decisions toward continuing or terminating a pregnancy with prenatal diagnosis of sex chromosome aneuploidy. We reviewed the records of patients with fetuses with sex chromosome aneuploidy between 1990 and 2001. A questionnaire survey of women who chose to terminate such pregnancies was designed to examine aspects of their decision-making process. Forty-nine of 89 pregnancies with sex chromosome aneuploidy were terminated (termination rate 0.55; 95% confidence interval 0.45-0.65). Pregnancies with abnormal ultrasound findings (14/16, 87%), with 45,X or 47,XXY karyotypes (26/36, 72%), and with nonmosaic karyotypes (30/48, 63%) were terminated significantly more often than pregnancies with normal ultrasound findings (35/73, 48%; P <.01), with 47,XXX or 47,XYY karyotypes (4/12, 33%; P <.05), and with mosaic karyotypes (5/25, 20%; P =.01). There was a trend (P =.136) toward a lower rate of termination from 67% to 36% across time, with a significant decrease from 67% to 7% in pregnancies with 47,XXX; 47,XYY; and mosaic karyotypes (P <.01), and no change in cases with 45,X and 47,XXY karyotypes (67% compared with 69%; P = 1.0). Abnormal sexual development and infertility were the greatest parental concerns related to termination. Fear of having a child with abnormal sexual development or infertility remains the major determinant of parental decision toward terminating pregnancy, resulting in consistently high termination rates across time in pregnancies with 45,X and 47,XXY karyotypes. In cases with 47,XXX; 47,XYY; and mosaic karyotypes, the declining termination rate across time is a consequence of recent studies reporting normal sexual development and fertility.

Community-Based Program for the Diagnosis and Prevention of Genetic Disorders in Cuba

The author’s experience of 20 years as director of the medical genetic services program in Cuba is presented. The setting of the infrastructure for equipment and the training of personnel for the medical genetic program began in 1981 in the city of Havana, and was progressively extended to cover the whole country in 1988. Between 1982 and 2002, 2.8 million pregnant women were tested for sickle cell carrier status, 96,000 carriers and 4,786 couples at risk were detected and offered genetic counseling and prenatal diagnosis. In the same period, the combination of maternal serum α-fetoprotein screening and fetal ultrasound led to the prenatal diagnosis of anomalies in several thousand fetuses. The accessibility to legal abortion, and the autonomous decisions by the majority of couples to terminate abnormal pregnancies reduced the prevalence of neural tube defects and sickle cell disease at birth by 90 and 65%, respectively, by 2002. In the span of approximately 20 years, 22,690 pregnant women at risk received prenatal chromosomal diagnosis. Newborn screening for phenylketonuria and congenital hypothyroidism was established. Genetic counseling was offered to every detected person or family at risk for genetic conditions. The network of medical genetic services established in the country received a very positive acceptance by the population. A very successful connection with the primary health care level was established.

“Prenatal diagnosis of mosaic ring chromosome 13 with anencephaly” in Prenatal Diagnosis 21(2), 102‐105

AbstractThe original article to which this Erratum refers was published in Prenatal Diagnosis 21(2) 2001, 102–105.

Nuchal Translucency and the Acceptance of Invasive Prenatal Chromosomal Diagnosis in Women Aged 35 and Older

Nuchal Translucency and the Acceptance of Invasive Prenatal Chromosomal Diagnosis in Women Aged 35 and Older

Nuchal translucency and the acceptance of invasive prenatal chromosomal diagnosis in women aged 35 and older

Objective: To investigate the effect of nuchal translucency screening on use of prenatal diagnosis for chromosomal abnormalities in women aged 35 and older. Methods: Two groups of women, referred to our center for prenatal karyotype diagnosis because of maternal age, were compared: one in 1995 and the other in 1999 after the introduction of nuchal translucency measurement. Each woman received nondirective genetic counseling, and for the 1999 group, nuchal translucency results were also discussed. Risks of transabdominal chorionic villi sampling (CVS) and amniocentesis, laboratory techniques, genetic results, and local experiences were discussed. Patient’s decision to undergo prenatal diagnosis, acceptance of the nuchal translucency test (in the 1999 group), and the rate of chromosomal abnormalities diagnosed by transabdominal CVS and amniocentesis, were considered. Results: Two hundred twenty-one of 982 (22%) women in the 1995 group and 421 of 1386 (30%) in the 1999 group, after nondirective genetic counseling declined invasive diagnosis ( P < .05). In the 1999 cohort, 1088 of 1089 (99.9%) women of appropriate gestational age had nuchal translucency measurement. Among women seen in 1995, 214 opted for transabdominal CVS (31%) and 476 (69%) for amniocentesis. Nineteen abnormal karyotypes were detected, six by transabdominal CVS and 13 (68.5%) by amniocentesis. In 1999, 266 women (29%) opted for transabdominal CVS and 650 (71%) for amniocentesis. Twenty abnormal karyotypes were detected, 13 (65%) by transabdominal CVS and seven (35%) by amniocentesis ( P < .05). Conclusion: Knowledge of nuchal translucency could lead to a decrease in the demand for invasive diagnosis and to a more frequent diagnosis by first-trimester transabdominal CVS.

Isolation of fetal cells from the maternal circulation: prospects for the non-invasive prenatal diagnosis.

The research into non-invasive and invasive prenatal diagnostic techniques developed almost in parallel. On the one hand the need was arising to ensure the birth of normal progeny in all cases, while on the other, it was not possible to eliminate the abortion risks connected with the invasiveness of amniocentesis (risk of abortion 1/200), chorion villi sampling, (risk of abortion 2%) and funicolocentesis (risk of abortion 3-4%). One of the first researchers in the non-invasive field was Adinolfi who published the earliest data in 1974 on the possibility of detecting three types of fetal cells in the maternal circulation using flow cytometry. Adinolfi suggested the possibility of using fetal cells present in the maternal circulation for prenatal diagnosis of chromosome or biochemical anomalies. Our review takes into consideration the latest methodological and technical progress in relation to the study of fetal cells in maternal circulation, without considering cells present in the endocervical canal where from the 8th week of pregnancy it is only possible to obtain trophoblast cells. This technique has since been abandoned due to the scarcity of cellular material available, the greater risk of contamination by cells of maternal origin, and also because the recovery of the cells is unpredictable, despite their potential use for the early non-invasive diagnosis of sex. The following issues are addressed in this review: the characterization of the fetal cell types present in the maternal circulation, the methods of their separation and enrichment, and the methods of genetic diagnostics applied.

Prenatal diagnosis of a mosaic extra structurally-abnormal chromosome by spectral karyotyping

A de novo mosaic extra structurally abnormal chromosome (ESAC) was detected in 33 per cent of cultured amniotic fluid cells from a pregnant woman. Neither Q-banding nor fluorescence in situ hybridization (FISH) employing a DNA probe for nucleolar organizer region demonstrated the presence of satellites on the ESAC. Spectral karyotyping (SKY) was performed in this prenatal case and led to a quick and accurate determination of the ESAC as chromosome 14 in origin. The SKY finding was confirmed by conventional FISH analysis using a chromosome 14 specific painting probe. Subsequent hybridizations with a centromeric probe and a 14q subtelomeric probe were also performed to further characterize the ESAC. Absence of (TTAGGG)n sequence on the ESAC, determined postnatally, suggested it is a ring chromosome 14. Genetic counselling concerning these findings was provided to the parents who chose to continue the pregnancy. The male infant had no apparent abnormal phenotype at birth.

Prenatal diagnosis of ring chromosome 14 after intracytoplasmic sperm injection

To collect extensively abnormal cytogenetic results in pregnancies obtained after intracytoplasmic sperm injection (ICSI). Case report. University Hospital of Nantes, France. A couple with 5 years of primary infertility and severe male factor undergoing ICSI procedure. Ultrasound-guided transvaginal follicular aspiration, amniocentesis, and medical abortion. Serum levels of E2, beta-hCG, and fetal chromosomal karyotype. Ultrasonic observation at 12 weeks revealed an 8-mm thick cystic hygroma in the nuchal area. Because the karyotypic analysis was [46,XX,r(14)/45,XX,-14], medical abortion was performed at 14 weeks, after the patients gave their informed consent. According to the prevalence of this unusual chromosomal abnormality in humans, such abnormal cytogenetic results have to be collected extensively to assess the feasibility of using ICSI procedure.

Prenatal diagnosis of ring chromosome 6

An amniocentesis was performed on a gravida 1, para 0 23-year-old female because of high maternal serum alpha-fetoprotein and nuchal thickening/cystic mass apparent on the fetal ultrasound. Detailed ultrasound examination revealed multiple anomalies including brain abnormalities. The fetus was found to have a mosaic female karyotype: 45,XX, - 6/46,XX,r(6) (p25q27) (62 per cent:38 per cent). This is the first report of a prenatally diagnosed case of ring chromosome 6.

Familial pericentric inversion incidentally detected at prenatal diagnosis

A case of familial heterozygous pericentric inversion of chromosome 1 [inv(1)(p13q23)] is presented. The inversion was incidentally detected in a fetus whose mother received prenatal chromosomal diagnosis due to her age (40 years old), and thereafter the same inversion was detected in the father whose phenotype was normal. No abnormalities were found in the phenotype of the newborn carrier. Semen analysis of the father revealed normal findings. The couple had no history of spontaneous abortion.

Der Triple-Test

Until the late 80s advanced maternal age was the main indication for prenatal chromosomal diagnosis. The triple test has introduced a noninvasive method for all women to determine the risk of chromosomal abnormality. Not only women aged over 35 years, but also those less than 35 years of age may benefit from the triple test. An exactly performed triple test will allow a diagnosis in 70% of all cases with trisomy 21. Additionally, a positive triple test will be found in 9% of all screened women. 1-2% of the women with a positive triple test will exhibit a fetus with trisomy 21. A false-negative result will be found in 0.1%. Beside trisomy 21, the triple test allows also the diagnosis of pregnancies with a high risk of trisomy 18 and Turner syndrome. The value of the triple test is mainly determined by the quality of the laboratory and the exactness of the determination of the gestational age, which is done mainly by means of ultrasound. Ultrasound investigation also provides information about structural abnormalities. In future the triple test will increase in accuracy and it will be performed in the first trimester.

The Outcome of Pregnancy and Prenatal Chromosomal Diagnosis of Fetuses in Couples Including a Translocation Carrier

In order to evaluate the relation between chromosomal translocation and the outcome of pregnancy, 50 couples were examined. Subjects consisted of 35 couples that included a reciprocal translocation carrier; 13 included a Robertsonian translocation carrier and 2 included a carrier of a mosaic reciprocal translocation. The reasons for performing chromosomal examinations were mainly infertility and abnormality of neonates. The rates of miscarriages and neonatal abnormalities in prior pregnancies were significantly higher than the birth rate of morphologically normal newborns. The presence of a translocation is closely related to reproductive failure because of the chromosomal imbalance. However, prenatal chromosomal examination after the 15th gestational week in subsequent pregnancies revealed that almost half of the fetuses showed normal karyotypes and only 12.8 per cent of the fetuses showed a chromosomal imbalance. Many chromosomally imbalanced fetuses are spontaneously aborted before amniocentesis. The risk of chromosomal imbalance is relatively low in prenatal diagnosis, but partial trisomies of small rearrangements tend to be preserved.

Choroid plexus cysts diagnosed prenatally as an independent risk factor for cytogenetic abnormality

Zerres et al. (1992) state on the basis of six cases reported in the literature with trisomy 21 and choroid plexus cysts that "prenatally diagnosed choroid plexus cysts should in all cases be regarded as an indication for prenatal chromosomal diagnosis because additional abnormalities in trisomy 21 are sometimes absent in the second trimester" (emphasis added). But the fact that some reported trisomy 21 cases have choroid plexus cysts but no other ultrasonically detectable abnormalities is of uncertain relevance to clinical practice. One needs pertinent data on controls. The authors' reported data indicate only that the presence of choroid plexus cyst is at best an equivocal finding. They report that of 823 fetuses exhibiting developmental abnormalities defined as "growth retardation/malformation," 168 (20.4%) had a cytogenetic disorder. In the 25 of the 823 in which choroid plexus cysts were diagnosed, they report 5 (20%) in which there was a cytogenetic disorder. Thus, one may calculate that in those without choroid plexus cyst but with growth retardation/malformation, the proportion with cytogenetic abnormally actually is 163/798 = 20.4%, or actually slightly higher than in those with such cysts. This result casts significant doubt on the clinical utility of observation of the cyst, or the authors' conclusion cited above. Their data do tend, however, to support the inference that the presence of "abnormalities" in addition to choroid plexus cyst in those with "growth retardation," is suggestive of a cytogenetic defect, but primarily trisomy 18. Of the 11 with such additional abnormalities 5 (45%) had a cytogenetic defect, (4 with 47 + 18, one with 47 + 21), whereas one may calculate from the authors' data that none (0/14) of those without other defects had normal karyotype. This difference has a two-tailed probability of about 0.002, and is thus nominally significant. Unfortunately, interpretation of even these data from a clinical perspective requires knowledge of the level of intensity with which they scanned the ultrasound after finding choroid plexus cysts, and when in gestation malformation was noted. The likelihood of recognition of fetal malformation in ultrasound varies markedly with the size of the lesion, knowledge of the region likely to be affected, and the age of the fetus. Some abnormalities may be very difficult to diagnose and only recognized retrospectively on ultrasound after knowledge of presence of the malformation, or only at late stages of pregnancy, when, in many jurisdictions, a patient may no longer have the option to terminate pregnancy. At best the results suggest that in a conceptus with choroid plexus cyst and growth retardation, the presence of another malformation on ultrasound may increase the likelihood that a karyotypic abnormality is present. The precise nature of this increase in likelihood cannot be evaluated from the data.

The outcome of pregnancy and prenatal chromosomal diagnosis of fetuses in couples including a translocation carrier.

In order to evaluate the relation between chromosomal translocation and the outcome of pregnancy, 50 couples were examined. Subjects consisted of 35 couples that included a reciprocal translocation carrier; 13 included a Robertsonian translocation carrier and 2 included a carrier of a mosaic reciprocal translocation. The reasons for performing chromosomal examinations were mainly infertility and abnormality of neonates. The rates of miscarriages and neonatal abnormalities in prior pregnancies were significantly higher than the birth rate of morphologically normal newborns. The presence of a translocation is closely related to reproductive failure because of the chromosomal imbalance. However, prenatal chromosomal examination after the 15th gestational week in subsequent pregnancies revealed that almost half of the fetuses showed normal karyotypes and only 12.8 per cent of the fetuses showed a chromosomal imbalance. Many chromosomally imbalanced fetuses are spontaneously aborted before amniocentesis. The risk of chromosomal imbalance is relatively low in prenatal diagnosis, but partial trisomies of small rearrangements tend to be preserved.

Chromosomal findings in fetuses with prenatally diagnosed cysts of the choroid plexus.

Choroid plexus cysts were diagnosed in 25 out of 823 fetuses with prenatally diagnosed abnormalities (growth retardation/malformations). Among these, 5 revealed a chromosomal disorder (4 cases with trisomy 18 and one case with a translocation trisomy 21). Additional abnormalities, such as growth retardation, holoprosencephaly, hydrocephalus and club foot, were found in 6 out of the 20 fetuses with no chromosomal abnormality. All fetuses with a chromosomal disorder revealed further typical prenatally recognizable abnormalities. Our observation indicates that prenatally diagnosed choroid plexus cysts should be considered as an indication for prenatal chromosomal diagnosis, although the risk of there being an underlying chromosomal disorder is low in cases with no additional abnormalities.