Karyotype Confirmation Research Articles

A young girl with right ovarian torsion and left ovarian ectopy

BackgroundMayer-Rokitansky-Küster-Hauser (MRKHS) syndrome refers to congenital hypoplasia/aplasia of the uterus, the cervix and the upper 2/3 of the vagina, in females with normal ovaries and fallopian tubes, secondary sexual characteristics and 46 XX karyotype. This condition originates from abnormal development of Müller’s paramesonephric ducts in the early stages of embryonic development. Kidney agenesis or malformations are the most commonly associated with unilateral kidney agenesis. Ovaries may be ectopic in 16–19% of MRKHS patients. Primary amenorrhoea, due to the absence of the uterus, is the most common presentation. Female karyotype confirmation is mandatory to differentiate it from complete androgen insensitivity syndrome and 17-alpha-hydroxylase deficiency. The management of MRKHS is multidisciplinary in order to encompass psychological, medical and surgical issues.Case presentationA four-year-old girl, presented to the emergency department complaining of left groin swelling noted 2 days earlier. The patient had recently been evaluated for an episode of acute abdominal pain and vomiting, with a final diagnosis of right ovarian torsion. At that time, the ultrasound imaging was not able to identify the left kidney, the left ovary and uterus. Surgical abdominal exploration confirmed the right ovarian torsion and was not able to identify the left kidney and the left ovary. Only a remnant of the uterus was present. Therefore, the right ovary was removed, and a diagnosis of MRKHS was made. Ultrasound imaging showed a left inguinal hernia. The hernial sac consisted of a solid oval vascularized formation suggestive of an annexe. The patient underwent a surgical procedure to correct the left inguinal hernia. In the operating setting, the presence of a vascularized, ectopic ovary carrying the tuba inside the hernial sac was observed.ConclusionsIn front of a patient with ovarian torsion and anatomical features suggestive of MRKHS, both the ovaries should always be searched for, with a high suspicion threshold for extrapelvic ovary. Identifying the ectopic ovary, in this case, helped to preserve patient fertility, avoiding a possible torsion.

Cytogenetic analysis of 3387 umbilical cord blood in pregnant women at high risk for chromosomal abnormalities

BackgroundCordocentesis in our practice is most commonly indicated for rapid karyotyping in the second or third trimester and is regarded as the gold standard for foetal chromosomal aberration diagnosis in pregnancies at high risk for chromosomal abnormalities. In this study, we investigated 3387 umbilical cord blood samples for karyotyping from pregnant women who underwent cordocentesis and explored the pregnancy outcomes of foetal sex chromosome mosaicism and chromosomal polymorphism.ResultsOut of the 3387 samples, 182 abnormal karyotypes were detected. Ultrasound soft markers were the most common prenatal diagnostic indication, but the detection rate of abnormal karyotypes was 2.02%, while it was 46.97% in the genome-wide NIPT-positive group. The rate of aneuploidy was lower in the soft marker group than in the other groups. Out of 16 cases with sex chromosome mosaicism, three pregnant women with foetuses with a lower proportion of sex chromosome mosaicism delivered healthy foetuses; the foetus with karyotype 46,X,i(Y)(q10)[20]/45,X[6] showed unclear genitals. Three foetuses with chromosomal polymorphisms had postnatal disorders.ConclusionsNIPT should not be recommended as the first-tier screening for chromosomal aberration for pregnancies with ultrasound soft markers or pathological ultrasound findings, but NIPT can be considered an acceptable alternative for pregnancies with contraindications to cordocentesis or the fear of procedure-related foetal loss. Mosaicism found in amniotic fluid cell culture requires further cordocentesis for karyotype confirmation, and the continuation of pregnancy is safe when a normal karyotype is identified in foetal blood culture. Further genetic testing and parental karyotype analysis are needed for foetal chromosomal polymorphisms.

EP05.03: An atypical case of Turner syndrome

Turner syndrome is a genetic disease with a karyotype of 45, X or 46, XX/45, X (mosaicism). 1/2500 female live births are affected, although 15% of spontaneous miscarriages show an X monosomy and only 1% of fetuses will survive to term. Typical prenatal findings are nuchal cystic hygroma, nonimmune hydrops, and renal and cardiac abnormalities. However, neither sonography nor maternal serum screening can be considered diagnostic of Turner syndrome, and karyotype confirmation is mandatory. A 38-year-old III gravida II para presented for first trimester screening in 13 gestational weeks. The first child was born with biliar atresia and needed living liver donation at the age of 3 weeks. The 2nd child is healthy. This fetus presented with a nuchal fold of 3.3.mm, generalised edema and an early IUGR at a CRL of 55mm. The nasal bone was hypoplastic. The fetus showed hypertelorism, low set ears and a strawberry shaped head. The IT was not visible and a sacral spina bifida was detected. Besides an omphalocele, there was a congenital heart defect, suspicious for TOF with pericardial effusion, cardiomegaly, VSD, overriding aorta and suspected pulmonary stenosis. CVS was performed but probably contaminated by maternal cells. In the framework of scientific research postnatal molecular karyotyping could surprisingly confirm 45/X0 twice. In conclusion, as our case shows, Turner syndrome can present with a broad heterogenity of signs and symptoms. The wide range of prenatal features indicates that a number of different X-located genes are responsible for the complete phenotype. Nevertheless affected fetuses show a substantial number of early-onset signs that can be detected in the first trimester, i.e. cystic hygroma, fetal hydrops, cardiac defects and increased nuchal translucency and can be diagnosed in early pregnancy. The difference in the appearance of NT in each chromosomal defect may reflect the heterogeneity of causes, hence invasive diagnostics is mandatory. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Patient choice and clinical outcomes following positive noninvasive prenatal screening for aneuploidy with cell-free DNA (cfDNA).

Evaluate patient choices and outcomes following positive cfDNA. Retrospective cohort study of women with positive cfDNA through two academic centers between March 2012 and December 2014. Patients were screened based on ACOG indications. Medical records reviewed for counseling, ultrasound findings, diagnostic testing, karyotype and outcome. CfDNA was positive in 114 women; 105 singletons and 9 twin pairs. CfDNA was positive for autosomal trisomy (21, 18, 13) in 96 (84.2%) and sex chromosome aneuploidy in 18 (15.8%). Certified genetic counselors performed 95% of post-cfDNA counseling. Prenatal diagnostic testing was pursued by 71/114 (62%). Karyotype was available in 91/105 (86.7%) singletons and confirmed aneuploidy in 75/91 (82.4%); the PPV of cfDNA with any ultrasound finding was 93.6% versus 58.6% without a finding. An abnormal sonographic finding was seen in 4/16 (25%) singletons with false positive cfDNA. Fetal termination occurred in 53/79 (67%) singletons and 3/5 (60%) twins with prenatal abnormal or unknown karyotype for autosomal trisomy. Eleven fetuses (11/56, 19.6%) were terminated for suspected autosomal trisomy without karyotype confirmation. Patient choices following positive cfDNA are varied. Ultrasound modifies the PPV of cfDNA. Termination rates for aneuploidy are not higher than historical controls. Recommendation for karyotype confirmation prior to termination is not universally followed. © 2016 John Wiley & Sons, Ltd.

Detection of triploid, molar, and vanishing twin pregnancies by a single-nucleotide polymorphism–based noninvasive prenatal test

We sought to determine the ability of single-nucleotide polymorphism-based noninvasive prenatal testing (NIPT) to identify triploid, unrecognized twin, and vanishing twin pregnancies. The study included 30,795 consecutive reported clinical cases received for NIPT for fetal whole-chromosome aneuploidies; known multiple gestations were excluded. Cell-free DNA was isolated from maternal blood samples, amplified via 19,488-plex polymerase chain reaction, and sequenced. Sequencing results were analyzed to determine fetal chromosome copy number and to identify the presence of additional fetal haplotypes. Additional fetal haplotypes, indicative of fetal triploidy, vanishing twin, or undetected twin pregnancy, were identified in 130 (0.42%) cases. Clinical confirmation (karyotype for singleton pregnancies, ultrasound for multifetal pregnancies) was available for 58.5% (76/130) of cases. Of the 76 cases with confirmation, 42.1% were vanishing twin, 48.7% were viable twin, 5.3% were diandric triploids, and 3.9% were nontriploid pregnancies that lacked evidence of co-twin demise. One pregnancy had other indications suggesting triploidy but lacked karyotype confirmation. Of the 5 vanishing twin cases with a known date of demise, 100% of losses occurred in the first trimester; up to 8 weeks elapsed between loss and detection by NIPT. This single-nucleotide polymorphism-based NIPT successfully identified vanished twin, previously unrecognized twin, and triploid pregnancies. As vanishing twins are more likely to be aneuploid, and undetected residual cell-free DNA could bias NIPT results, the ability of this method to identify additional fetal haplotypes is expected to result in fewer false-positive calls and prevent incorrect fetal sex calls.

Clinical experience and follow-up with large scale single-nucleotide polymorphism–based noninvasive prenatal aneuploidy testing

We sought to report on laboratory and clinical experience following 6 months of clinical implementation of a single-nucleotide polymorphism-based noninvasive prenatal aneuploidy test in high- and low-risk women. All samples received from March through September 2013 and drawn ≥9 weeks' gestation were included. Samples that passed quality control were analyzed for trisomy 21, trisomy 18, trisomy 13, and monosomy X. Results were reported as high or low risk for fetal aneuploidy for each interrogated chromosome. Relationships between fetal fraction and gestational age and maternal weight were analyzed. Follow-up on outcome was sought for a subset of high-risk cases. False-negative results were reported voluntarily by providers. Positive predictive value (PPV) was calculated from cases with an available prenatal or postnatal karyotype or clinical evaluation at birth. Samples were received from 31,030 patients, 30,705 met study criteria, and 28,739 passed quality-control metrics and received a report detailing aneuploidy risk. Fetal fraction correlated positively with gestational age, and negatively with maternal weight. In all, 507 patients received a high-risk result for any of the 4 tested conditions (324 trisomy 21, 82 trisomy 18, 41 trisomy 13, 61 monosomy X; including 1 double aneuploidy case). Within the 17,885 cases included in follow-up analysis, 356 were high risk, and outcome information revealed 184 (51.7%) true positives, 38 (10.7%) false positives, 19 (5.3%) with ultrasound findings suggestive of aneuploidy, 36 (10.1%) spontaneous abortions without karyotype confirmation, 22 (6.2%) terminations without karyotype confirmation, and 57 (16.0%) lost to follow-up. This yielded an 82.9% PPV for all aneuploidies, and a 90.9% PPV for trisomy 21. The overall PPV for women aged ≥35 years was similar to the PPV for women aged <35 years. Two patients were reported as false negatives. The data from this large-scale report on clinical application of a commercially available noninvasive prenatal test suggest that the clinical performance of this single-nucleotide polymorphism-based noninvasive prenatal test in a mixed high- and low-risk population is consistent with performance in validation studies.

Cloacal exstrophy: An epidemiologic study from the International Clearinghouse for Birth Defects Surveillance and Research

Cloacal exstrophy presents as a complex abdominal wall defect thought to result from a mesodermal abnormality. Anatomically, its main components are Omphalocele, bladder Exstrophy and Imperforate anus. Other associated malformations include renal malformations and Spine defects (OEIS complex). Historically, the prevalence ranges from 1 in 200,000 to 400,000 births, with higher rates in females. Cloacal exstrophy is likely etiologically heterogeneous as suggested by its recurrence in families and occurrence in monozygotic twins. The defect has been described in infants with limb-body wall, with trisomy 18, and in one pregnancy exposed to Dilantin and diazepam. Due to its rarity, the use of a nonspecific diagnostic code for case identification, and lack of validation of the clinical findings, cloacal exstrophy remains an epidemiologic challenge. The purpose of this study was to describe the prevalence, associated anomalies and maternal characteristics among infants born with cloacal exstrophy. We used data from the International Clearinghouse for Birth Defects Surveillance and Research submitted from 18 birth defect surveillance programs representing 24 countries. Cases were clinically evaluated locally and reviewed centrally by two authors. Cases of persistent cloaca were excluded. A total of 186 cases of cloacal exstrophy were identified. Overall prevalence was 1 in 131,579 births: ranging from 1 in 44,444 births in Wales to 1 in 269,464 births in South America. Live birth prevalence was 1 in 184,195 births. Prevalence ratios did not vary by maternal age. Forty-two (22.6%) cases met the criteria for the OEIS complex, whereas 60 (32.3%) were classified as OEI and 18 (9.7%) as EIS (one with suspected VATER (0.5%)). Other findings included two cases with trisomy 13 (one without a karyotype confirmation), one with mosaic trisomy 12 (0.5%), one with mosaic 45,X (0.5%) and one classified as having amnion band sequence (0.5%). Twenty-seven (14.5%) infants had other anomalies unrelated to cloacal exstrophy. Cloacal exstrophy is a rare anomaly with variability in prevalence by geographic location. The proportion of cases classified as OEIS complex was lower in this study than previously reported. Among all cases, 54.8% were reported to have an omphalocele.

Treatment of scoliosis in patients affected with Prader-Willi syndrome using various techniques

BackgroundThe incidence of spinal deformity in children with Prader-Willi syndrome (PWS) is high, with 86% of these patients found to have a significant structural scoliosis; however, there are very few case reports describing surgical treatment for this deformity.MethodsThe authors reviewed a case series consisting of 6 patients who underwent spine surgery for scoliosis. Children's mean age at index surgery was 12 years and 10 months (range, 10 to 15 yrs). Clinical evaluation revealed the typical phenotypic features of the PWS in all of the patients; 4 subjects had a karyotype confirmation of PWS. Major structural curves showed preoperative mean Cobb angles of 80.8° (range, 65° to 96°). Hybrid instrumentation with sublaminar wires, hooks and screws was used in the first 2 patients, while the remaining 4 were treated with titanium pedicle screw constructs.ResultsThe mean clinical and radiological follow-up was 3 years and 10 months (range, 2 years to 9 years). Major complication rate was 50%. One patient who developed a major intraoperative complication (paraparesis) prevented spinal fusion to be obtained: the neurologic deficit resolved completely after instrumentation removal. Solid arthrodesis and deformity correction in both coronal and sagittal plane was, however, achieved in the other 5 cases and no significant curve progression was observed at follow-up. Another major short-term complication was encountered 3 months after surgery in a patient who experienced the detachment of a distally located rod and required correction through revision surgery and caudal extension by one level. Cervico-thoracic kyphosis was seen in 1 patient who did not require revision surgery.ConclusionsSpine reconstructive surgery in patients with PWS is rare and highly demanding.The best method of reconstruction is posterior multilevel pedicle screw fixation. Moreover, even with modern techniques, the risk of complications is still high. These new techniques, however, have shown to improve the postoperative course by allowing for immediate mobilization without any brace or cast. The use of the growing rod techniques, requiring repeated surgeries, should be carefully evaluated in each single case.

Utility of Fetal Karyotype in the Evaluation of Phenotypically Abnormal Stillbirths

The objectives of this study are to test the hypothesis that stillbirths without aneuploidy-associated phenotypes have a low incidence of karyotypic abnormalities, similar among those with and without other anatomic defects. We employed a uniform postmortem protocol to examine fetuses and placentas in 962 consecutive stillbirths measuring > or =20 weeks in clinically determined gestational age submitted to the Women and Infants Hospital Division of Perinatal Pathology from 1990 through 2005. Classification of anatomic (macroscopic) abnormalities was based on a priori criteria. Anatomic fetal abnormalities were noted in 387 cases. Conventional karyotype analysis was successfully performed on 346 fetal tissue samples, 114 in anatomically normal and 232 in anatomically abnormal fetuses. The distribution of karyotypic abnormalities among cases with and without anatomic abnormalities was compared. Of the 962 stillbirths, 40% (387) had malformations. Tissue culture for karyotype analysis was attempted in 412 cases from both groups and failed in 66 cases (16%). At the 450 to 500-band resolution level, 60 of the remaining 346 karyotypes were abnormal. Of the 232 malformation cases with successful karyotyping, 59 had phenotypic attributes indicative of aneuploidy, all of which had later karyotype confirmation. Of the remaining 173 anomalous fetuses with karyotype analysis, only 1 demonstrated a karyotypic abnormality. All 114 karyotypes performed in stillbirths without anatomic abnormalities were normal. Among > or =20-week stillbirths, aneuploid karyotypes are uncommon except in fetuses with suspect phenotypes. The 95% probability estimates of karyotype abnormality in the phenotypically abnormal and normal stillbirths, 5.5% and 5.6%, respectively, do not differ. These data do not have sufficient power to detect a small difference in rates ofkaryotypic abnormalities between the 2 groups of > or =20-week stillbirths. However, this series indicates that this technology is uninformative among stillborn fetuses that lack aneuploidy phenotypes.

Going down a different road: first support and information needs of families with a baby with Down syndrome

To explore the experiences of families with a baby with Down syndrome at the time of diagnosis, and their preferences for information and support in the early period after diagnosis. A qualitative, interview-based study of 18 families living in Victoria with a child with Down syndrome born between 2002 and 2004 who had not been diagnosed with the syndrome before birth. Interviews were transcribed verbatim and interpretive content analysis was undertaken. Parental coping with the unexpected diagnosis of Down syndrome in their infant was influenced by the time interval between birth and disclosure of clinical suspicion of Down syndrome, the level of certainty of the attending physician at the time of disclosure, and the time interval between disclosure of clinical suspicion and confirmation of karyotype. Initial uncertainty and a delay in the diagnosis were detrimental to parental coping, as was premature communication of the news. Perinatal complications increased parental anxiety regarding their child's condition and future. Individual communication style of midwives and physicians was a powerful predictor of parental adaptation. Parental needs for support and information were facilitated through normalising postnatal care, ensuring privacy, and providing early access to peer support and up-to-date written information. Many parents would have appreciated access to a liaison worker. The experiences of parents in this study provide practice points for improving postnatal care with minimal changes to formal service systems.

Acute Promyelocytic Leukemia with T(15;17): Frequency of Additional Clonal Chromosome Abnormalities and FLT3

Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML) characterized by t(15;17)(q22;q21), a balanced reciprocal translocation involving PML and RARA genes. Studies conducted in animal models with PML/RARA suggest that this gene rearrangement is not sufficient for the development of APL, emphasizing the importance of additional mutations. Another gene that could be involved in APL leukemogenesis is FLT3, a Fms-like tyrosine kinase receptor which mutations have been observed in different AML subtypes as the internal tandem duplications (ITD), in around 18–37% of APL cases or less frequently, the D835Y mutation. The association of FLT3/ITD in APL gave rise to the proposition that it could provide a common class of cooperative mutation in the development of the disease. Indeed, APL represents 21% of all cases of AML with karyotype confirmation in our institution, located in São Paulo, Southeast region of Brazil. Bone marrow samples from 92 consecutive APL patients at diagnosis were enrolled in the study. Mean age was 29.5 years old, varying from 4 months to 67 years old, with the following age distribution: 35.7% of the patients were younger than 20 years old; 55.2% were between 20 and 49 years old and only 17.2% were older than 50 years. There were 50 males and 42 females. The WBC count demonstrated a wide variation, from severe leukopenia (<500 leukocytes/μL) until marked leukocytosis (174.600/μL), most of them presenting circulating blasts. Hemoglobin level varied from 3.7g/dL to 14g/dL and platelets counts were frequently low. Cases included five (5.4%) microgranular variant patients. We observed that 23 (25%) out of 92 cases presented chromosomal abnormalities in addition to t(15;17), among which trisomy 8 was the most frequent (21.7%, 5/23). Other abnormalities included tetraploidy, trisomy 6, trisomy 21 (non constitutional), nulissomy Y, ider(17q), trisomy 11, del(9)(q22q32), add(3)(p26), del(6)(p21), abnormalities of chromosome 7 and 1, t(1;3)(q21;q29); t(7;9)(q36;q31); monosomy of chromosomes 6, 7, 8 and 9; dup(1)(q23q42), del(10)(q24); add(7)(q36) and marker chromosomes. Seventy nine cases had enough DNA for complimentary molecular studies; in the remaining 13 cases we could not retrieve any DNA amount from fixed cells. Among those, FLT3/ITD was detected in 29 (36.7%), 5 of them showing additional karyotype abnormalities and D835Y mutation was present in only 2 (2.8%) of the cases. None of the two patients with D835Y showed additional chromosomal abnormality, but one of them presented ITD and D835Y mutation simultaneously at diagnosis. No correlation was found between age, sex, WBC count, hemoglobin level, platelet count or clinical symptoms and the presence or absence of additional karyotype abnormalities, FLT3-ITD and D835Y. The frequencies of additional karyotype abnormalities as well as FLT3/ITD in Brazilian APL patients were similar to those reported in several worldwide published papers. On the other hand, the incidence of D835Y was lower than that described elsewhere (2.8% versus 7% in AML or 5.7% in APL). So although Latin American population has an increased incidence of APL, it seems not to bear a higher frequency of clonal additional chromosome abnormalities or mutations in FLT3 gene. Moreover, FLT3/ITD was not over-represented in cases with additional chromosomal abnormalities (17.2% versus 36.7%, p=0,2), thus suggesting an independent role for each FLT3/ITD and extra clonal chromosomal abnormalities in t(15;17) APL. In the present study, a significant proportion of APL patients (56%) showed additional karyotype alterations and/or FLT3/ITD or D835Y mutation. In fact, one fourth of APL cases presented additional chromosomal abnormalities at diagnosis while 1/3 of the cases showed the FLT3/ITD and only two patients presented D835Y mutation. So, roughly more than one half of the cases presented at least one of the alterations investigated, raising the possibility that these abnormalities may be complimentary events to PML/RARA in the process of leukemogenesis. The influence of additional chromosomal abnormalities predisposing to genomic instability and cooperating with genetic mutations in acute leukemia still deserves investigation, since about 45% of APL cases have not been shown to bear any detectable molecular abnormality to date.

Sonographic features of the triploid fetus

The sonographic characteristics of six viable triploid fetuses, with gestational ages ranging from 16 to 33 weeks, are presented. Each pregnancy was associated with decreased amniotic fluid volume, a significant lag in biparietal diameter and femur length, and severe head-to-body disproportion. No placental abnormalities were noted on ultrasound and only one placenta demonstrated hydropic change (15% to 20% of villi) on pathologic examination. Since the nonmolar triploid fetus often presents with unexplained intrauterine growth retardation, identification of its characteristic sonographic features allows for karyotype confirmation and the avoidance of inappropriate obstetric management.

Trisomy 18, esophageal atresia, anomalies of the radius, and congenital hypoplastic thrombocytopenia.

Since the initial description of trisomy 17–18 as a clinical syndrome (1), a large number of reports have delineated a variety of its clinical and roentgen features (2–4). The combination of characteristic findings often permits diagnosis prior to chromosomal confirmation. We have recently observed three cases of trisomy 18 with unusual manifestations that warrant inclusion in the expanding clinical spectrum of this syndrome. These changes were esophageal atresia, malformations of the radius, and congenital thrombocytopenia. Radial anomalies were present in all three infants, esophageal atresia and thrombocytopenia in two. One child died within thirty hours after birth, and a chromosomal karyotype was not obtained. The clinical, roentgenological, and pathological findings, however, were characteristic of trisomy 18. Karyotype confirmation of trisomy 18 was obtained in the other two infants. CASE I: A 1600 g female was delivered by a 30-year-old mother following a forty-week gestation. Labor was induced because of polyhydramnios. At birth, the infant was in no distress. Multiple congenital anomalies, however, were apparent. The head was large, the chin receded, the mouth fish-like, and the ears low and posterior. There was marked flexion deformity of both wrists and incurving of the forearms. Only four fingers were present on the right hand. A harsh presystolic murmur was noted over the entire precordium. The infant regurgitated excessive amounts of mucus and, on the second day of life, roentgen examination revealed a distended proximal esophageal pouch with no air within the abdominal viscera (Fig. 1, A). Gastrografin was instilled, and the diagnosis of esophageal atresia without tracheoesophageal fistula was confirmed (Fig. 1, B). On the following day, an esophagostomy and gastrostomy were performed, with placement of a feeding tube. Roentgen study of the skeleton revealed a small narrow pelvis demonstrating the so-called antimongoloid configuration. The right arm (Fig. 1, C) exhibited hypoplasia of the radius and a curved ulna. Only four digits and four metacarpals were present. The first digit of the left hand (Fig. 1, D) was hypoplastic, and the second digit overlay the third. The middle and distal phalanges of the fifth digit were also hypoplastic. A V-shaped notch separated the fourth and fifth digits. An elongated skull was also noted, with a large posterior fossa and a small mandible. An intravenous urogram demonstrated a left-sided, crossed, fused ectopia with a double collecting system and double ureters draining the left kidney. The diagnosis of trisomy 18 was suggested, and chromosome configuration was obtained. The child did moderately well for approximately one month but gained little weight. During this time no hematological abnormalities were noted. At two months of age, she became dyspneic and cyanotic. X-ray examination of the chest showed a right upper lobe pneumonia and cardiac enlargement.