An infant with double trisomy (48,XXX, + 18)

We report on an infant with double trisomy 48,XXX, + 18. She presented with manifestations of trisomy 18: prominent occiput, microphthalmia, small mouth, micrognathia, malformed ears, congenital heart defect, overlapping fingers, talipes equinovarus, and rockerbottom feet. An extra palmar crease was present only on the right hand. This patient was alive at 12 months. The clinical manifestations are compared with those of 10 previosly reported cases. © 1994 Wiley-Liss, Inc.     

48,XXX, +18 double trisomy

An infant who died at 127 days with gross congenital deformities is described. Cytogenetic analysis showed double trisomy of 18 and X which was confirmed by autoradiography and fluorescent banding techniques.     

Ullrich-Turner phenotype with unusual manifestation in a patient with mosaicism 45,X/47,XX,+18

We report on a girl with Ullrich-Turner phenotype and 45,X/47,XX,+18 chromosomal mosaicism. Only two other patients with similar mosaicism have been reported, both girls with XY sex chromosome constitution. The face of the patient was highly asymmetric, the right side being almost normal, the left showing a typical Ullrich-Turner syndrome appearance. This clinical impression was strengthened by photographic doubling of both hemifaces. The patient had normal intelligence and did not show any stigmata of trisomy 18. © 1996 Wiley-Liss, Inc.     

Clinical,cytogenetic, and molecular findings in 45,X/47,XX,+18 mosaicism: Clinical report and review of the literature

We report cytogenetic and molecular findings performed in a patient with double mosaic aneuploidy. Chromosome analysis of amniotic fluid cells from a 17‐week‐old fetus was performed because of advanced maternal age. Two karyotypes were detected: 45,X and 47,XX,+18 (50:50%). The same cell lines were determined in uncultured and cultured amniocytes of a second amniotic fluid sample, in fetal lymphocytes, and in uncultured and cultured cells of achilles tendon by conventional cytogenetics and fluorescence in situ hybridization (FISH). In the different investigated tissues, the percentage of cells with 45,X karyotype ranged from 20–99% and the percentage of cells with 47,XX,+18 ranged from 1–80%. The pregnancy was terminated at 22 + 0 weeks because of a severe cardiac malformation. Pathologic examination showed a fetus with aspects typical for manifestation of trisomy 18 and monosomy X, especially in the internal organs. The parent and cell stage of origin was determined by short tandem repeat typing and revealed a maternal meiotic division error that led to trisomy 18, as well as a somatic loss of a paternal sex chromosome. Only two other patients with the same mosaicism have been reported so far. Genetic counseling and prognosis remains challenging. © 2002 Wiley‐Liss, Inc.     

Retrieval of aneuploidy by fish-technique in a case with 46,XX/47,XXX/47,XX,+8

Summary We report on a 46 year old female with a new chromosomal finding [46,XX/47,XXX/47,XX,+8] who was referred for ovarian failure. The clinical presentation was highly unusual and the patient does not exhibit the characteristic phenotype of trisomy 8 syndrome. Interphase cytogenetics using FISH-technique revealed discrepancies with a different population of cells when compared with its metaphase index. Therefore, it is advised that patients with mosaic karyotypes should be evaluated by analyzing metaphase as well as interphase nuclei labeled with chromosome specific molecular tags, especially in the situations where the incidence of a mosaic cell line is very low. Nevertheless, in a cost-conscious environment, we must exercise caution prior to making universal recommendations concerning the usefulness of medical devices which are increasing at a logarithmic rate.     

The impact of cardiac surgery in patients with trisomy 18 and trisomy 13 in Japan

Congenital heart defects (CHD) are very common in patients with trisomy 18 (T18) and trisomy 13 (T13). The surgical indication of CHD remains controversial since the natural history of these trisomies is documented to be poor. To investigate the outcome of CHD in patients with T18 and T13, we collected and evaluated clinical data from 134 patients with T18 and 27 patients with T13 through nationwide network of Japanese Society of Pediatric Cardiology and Cardiac Surgery. In patients with T18, 23 (17%) of 134 were alive at this survey. One hundred twenty-six (94%) of 134 patients had CHDs. The most common CHD was ventricular septal defect (VSD, 59%). Sixty-five (52%) of 126 patients with CHD developed pulmonary hypertension (PH). Thirty-two (25%) of 126 patients with CHD underwent cardiac surgery and 18 patients (56%) have survived beyond postoperative period. While palliative surgery was performed in most patients, six cases (19%) underwent intracardiac repair for VSD. Operated patients survived longer than those who did not have surgery (P < 0.01). In patients with T13, 5 (19%) of 27 patients were alive during study period. Twenty-three (85%) of 27 patients had CHD and 13 (57%) of 27 patients had PH. Atrial septal defect was the most common form of CHD (22%). Cardiac surgery was done in 6 (26%) of 23 patients. In this study, approximately a quarter of patients underwent surgery for CHD in both trisomies. Cardiac surgery may improve survival in selected patients with T18.     

Three cell line mosaicism involving structural and numerical abnormalities of chromosome 18 in a 3.5‐Year‐old girl: 47,XX,+18/47,XX,+del(18)(q22)/46,XX

We report on a 3.5‐year‐old girl with a mosaic karyotype including full trisomy 18, normal cells and a majority of cells with partial trisomy involving an extra chromosome 18 deleted at band q22. She had cardiac and CNS anomalies, dysmorphic facial features failure to thrive and developmental delay. A gastrostomy tube was placed at 2 years of age. The combination of improved nutrition and optimal developmental therapy has led to her sitting supported, attempting to stand and enhancement of her cognitive and non‐verbal communication abilities. Molecular investigation of the patient and her parents using microsatellite analysis has led to the conclusion that, as expected, the additional copy of chromosome 18 constituting the full trisomic cell line is maternal meiosis I in origin. The data, however, indicate that in the trisomic cell line containing the deleted chromosome 18q, the structurally abnormal 18 was of paternal origin. We think this case is the first described with both structural and numerical trisomic mosaicism involving chromosome 18 in a liveborn infant. We propose a mechanism of origin and review the literature, comparing the clinical presentation of this case with individuals having full or partial trisomy 18. © 2001 Wiley‐Liss, Inc.     

Natural outcome of trisomy 13, trisomy 18, and triploidy after prenatal diagnosis

Trisomy 13, trisomy 18, and triploidy belong to the chromosomal abnormalities which are compatible with life, but which are also associated with a high rate of spontaneous abortion, intrauterine death, and a short life span. This study was conducted to analyze natural outcome after prenatal diagnosis of these disorders. Between January 1, 1999 and December 31, 2009, we investigated all amniocenteses and chorionic villus biopsies carried out at our department. All cases with fetal diagnosis of triploidy, trisomy 13, and 18 were analyzed, with a focus on cases with natural outcome. Overall, 83 (78%) cases of pregnancy termination and 24 (22%) patients with natural outcome (NO) were identified. The NO group included 15 cases of trisomy 18, six cases of triploidy, and three cases of trisomy 13. No case of triploidy was born alive. The live birth rate was 13% for trisomy 18 and 33% for trisomy 13. The three live-born infants with trisomy 13 and 18 died early after a maximum of 87 hr postpartum. Our data are consistent with the literature concerning outcome of triploidy, with none or only a few live births. Analyzes of trisomy 13 and 18 indicate a very short postnatal life span. Different study designs and diverse treatment strategies greatly affect the fetal and neonatal outcome of fetuses with triploidy, trisomy 13, and 18. More studies analyzing natural outcome after prenatal diagnosis of these chromosomal abnormalities are needed. Non-termination of these pregnancies remains an option, and specialists advising parents need accurate data for counseling.     

Natural history of trisomy 18 and trisomy 13: II. Psychomotor development

Developmental data were abstracted from medical records on 50 trisomy 18 individuals ranging in age from 1 to 232 months and 12 trisomy 13 individuals ranging in age from 1 to 130 months. Data on the age when trisomy 18 and trisomy 13 children achieved developmental skills were collected from a larger group of 62 trisomy 18 individuals and 14 trisomy 13 individuals whose families filled out parent questionnaires. Developmental quotient (DQ), defined as developmental age divided by chronological age, averaged 0.18 for trisomy 18 and 0.25 for trisomy 13. There was a dramatic drop in DQ from infancy to later childhood. The highest DQs and the greatest variation in DQs were in the first 2–3 years of life. Developmental ages in 7 skill areas were significantly different, with daily living and receptive language having the highest values and motor and communication skills having the lowest. When chronological age was taken into account, there was no significant difference in DQs in the same 7 skill areas, although there was a trend that was similar to the pattern of differences with developmental age. Older children could use a walker, understand words and phrases, use a few words and/or signs, crawl, follow simple commands, recognize and interact with others, and play independently. Walking and some toileting skills were also reported for trisomy 13. Although individuals with trisomy 18 and trisomy 13 were clearly functioning in the severe to profound developmentally handicapped range, they did achieve some psychomotor maturation and always continued to learn. © 1994 Wiley-Liss, Inc.     

Survival in trisomy 18

Prenatal diagnosis of trisomy 18 by amniocentesis in the latter half of pregnancy is now a common event. Accurate prognostic information is crucial for families making decisions about delivery management. Three recently published studies showed much shorter survival for trisomy 18 than was reported by earlier papers. For this reason, we studied trisomy 18 survival. We examined chromosome laboratory records to find all trisomy 18 diagnoses made in Utah between 1979 and 1988. Death certificates and hospital records were used to determine survival. We found 64 live-born cases with trisomy 18 out of 388,563 total births over the 10-year period, a prevalence of 1/6071. Our results show a median survival of 4 days and a 1 week survival of 45%, similar to that reported in the 3 recent studies. However, we had a significantly greater survival at 6 months (9% in Utah versus 3% in Denmark) and 1 year (5% versus 0 in the 3 studies). In contrast to recent studies, earlier investigations showed 80% survival at 2 weeks and 8% at 1 year. It is not surprising that recent studies show shorter survival, since in the 1960s the diagnosis was typically not made until age 2 months. With prenatal and neonatal diagnosis many cases which would have died prior to detection in earlier times are now diagnosed. The longer survival discrepancies are more difficult to explain, but may simply be due to small numbers. © 1994 Wiley-Liss, Inc.     

Double mosaic aneuploidy: 45, X/47,XY,+8 in a male infant

We report on a 13-month-old boy with abnormalities consistent with mosaic trisomy 8 syndrome and male genitalia with partial peno-scrotal transposition without hypospadias, a retractile left testis in inguinal canal, and an absent right testis. A voiding cystourethrogram showed an outpouching close to the lower right side of the bladder (utriculum) and bilateral hydronephrosis secondary to vesicoureteral reflux. Peripheral blood karyotype was 45,X/47,XY,+8. The karyotype of cultured skin fibroblasts was 47,XY,+8 with no 45,X cells detected among 20 cells counted. Tissues removed during surgery documented a 45,X/47,XY,+8 complement in the left testicle and utriculum, but only a 45,X line among 20 cells counted from vas deferens tissue. A possible mechanism for the origin of this previously unreported mosaicism might be an abnormal zygote with a 47,XY,+8 complement with subsequent simultaneous loss of chromosome Y and 8 in a cell at a very early embryonic stage. © 1992 Wiley-Liss, Inc.     

Natural history of trisomy 18 and trisomy 13: I. Growth,physical assessment,medical histories,survival, and recurrence risk

The natural history of trisomy 18 and trisomy 13 was investigated using data derived from parent questionaires and medical records from 98 families with an index case of trisomy 18 and 32 families with an index case of trisomy 13. Data are presented on pregnancy, delivery, survival, medical complications, immunizations, growth, cause of death, cytogenetics, and recurrence risk. Half of the trisomy 18 babies were delivered by C-section. Fetal distress was a factor in half, and the only reason in a third of C-section deliveries. One minute Apgar scores were significantly lower in C-section and breech deliveries. There were more small for gestational age babies than in the general population, but most of the low birth weight new borns were small for gestational age, unlike the general population. Survival in this group of children was better than in other studies due to ascertainment bias. There were more girls than boys at all ages for both conditions, and the sex ratio decreased with time. Growth curves for length, weight, head circumference, and weight vs height are provided. Long-term survival did not appear to be due to mosaicism. We found no adverse reactions attributable to immunizations. At age 1 year there was an average of approximately 2 operations per living child. We report the second case of successful major cardiac surgery in a trisomy 18 child. Almost 70% of deaths were attributed to cardiopulmonary arrest. The sibling recurrence risk for trisomy 18 or trisomy 13 was 0.55%. © 1994 Wiley-Liss, Inc.     

Trisomy 13/trisomy 18 mosaicism in an infant

Cytogenetic analysis of amniotic fluid cells from a 31-week-old fetus suffering from polyhydramnios revealed that there were two cell lines, each with either trisomy 13 or trisomy 18. We studied the origin and mechanism of formation of this unique mixoploidy by tracing chromosomal heteromorphisms as genetic markers, and showed no discordance of parent-child transmission between the two cell lines in any of the heteromorphisms examined. The result indicated that the mixoploidy is not chimerism but mosaicism and that the mechanism of mosaic development is most likely due to two non-disjunctional events which had occurred independently at the two-cell stage of the zygote. A girl was born at the 38th gestational week and her clinical features were mainly those for trisomy 13. Chromosome analysis of the newborn confirmed +13/+18 mosaicism in fibroblasts from the skin and chorionic plate, while cord blood lymphocytes and chorionic villus cells showed only the +18 cell line.     

A mildly retarded woman with 46,XX/47,XX,+18 mosaicism

We describe a mildly retarded woman with trisomy 18 mosaicism. The phenotype did not suggest trisomy 18, but the mild mental retardation, asymmetric face with bushy eyebrows and thick lips, short stature, and older maternal age raised the suspicion of a chromosomal cause for her condition.     

Pregnancy: Abnormal amniotic fetal antigen 2 concentrations in trisomy 18 and trisomy 21

Fetal antigen 2 (FA-2) is a human protein, first identifiedin amniotic fluid, and shown to be identical to the aminopropeptideof the ₁ chain of collagen type I. It exists in several differentsize and charge forms. In the present study, FA-2 was measuredin amniotic fluid using two different assays: a rocket lineimmunoelectrophoretic assay which measured total FA-2, and aradioimmunoassay which was specific for the high molecular massforms of FA-2. Both assays gave similar results. FA-2 concentrationswere measured in amniotic fluid samples collected fi om normalpregnancies at 10–23 weeks gestation; they we e shownto rise steeply from 10–14 weeks, peak at 17 weeks andthen fall slightly by 23 weeks. Comparison between amnioticfluid from normal pregnancies and pregnancies affected by trisomy,showed significantly higher FA-2 concentrations in trisomy 21and significantly lower concentrations in trisomy 18.