Solid tumor screening recommendations in trisomy 18
Am J Med Genet A. 2019 Mar;179(3):455-466. doi: 10.1002/ajmg.a.61029. Epub 2019 Jan 13.
Farmakis SG1, Barnes AM2, Carey JC3, Braddock SR4.
Abstract The purpose of this study was to determine whether trisomy 18 patients are at an increased risk of tumor development and require formal tumor screening recommendations. A literature search of trisomy 18 patients with reports of tumors or malignancies, and compilation of all previously reported as well as new unreported cases was performed. 67 patients with trisomy 18 were found to have documented malignancies. 44 patients had hepatoblastomas, 21 patients had Wilms tumors, one patient had a functional neurogenic neoplasia, and one patient had Hodgkins lymphoma. The increasing numbers of reported malignancies in patients with trisomy 18 supports the indication for an early screening process. Specific screening recommendations are outlined consisting of imaging exams and laboratory values performed at specific intervals. © 2019 Wiley Periodicals, Inc. KEYWORDS: Wilms tumor; hepatoblastoma; risk; screening; trisomy 18 PMID: 30637956 DOI: 10.1002/ajmg.a.61029
Goel N, Morris JK, Tucker D, de Walle HEK, Bakker MK, Kancherla V, Marengo L, Canfield MA, Kallen K, Lelong N, Camelo JL, Stallings EB, Jones AM, Nance A, Huynh MP, Martínez-Fernández ML, Sipek A, Pierini A, Nembhard WN, Goetz D, Rissmann A, Groisman B, Luna-Muñoz L, Szabova E, Lapchenko S, Zarante I, Hurtado-Villa P, Martinez LE, Tagliabue G, Landau D, Gatt M, Dastgiri S & Morgan M. (2019). Trisomy 13 and 18-Prevalence and mortality-A multi-registry population based analysis. Am. J. Med. Genet. A , 179, 2382-2392. PMID: 31566869 DOI.
Trisomy 13 and 18-Prevalence and mortality-A multi-registry population based analysis. Goel N1,2, Morris JK3, Tucker D2, de Walle HEK4, Bakker MK4, Kancherla V5, Marengo L6, Canfield MA6, Kallen K7, Lelong N8, Camelo
Abstract The aim of the study is to determine the prevalence, outcomes, and survival (among live births [LB]), in pregnancies diagnosed with trisomy 13 (T13) and 18 (T18), by congenital anomaly register and region. Twenty-four population- and hospital-based birth defects surveillance registers from 18 countries, contributed data on T13 and T18 between 1974 and 2014 using a common data-reporting protocol. The mean total birth prevalence (i.e., LB, stillbirths, and elective termination of pregnancy for fetal anomalies [ETOPFA]) in the registers with ETOPFA (n = 15) for T13 was 1.68 (95% CI 1.3-2.06), and for T18 was 4.08 (95% CI 3.01-5.15), per 10,000 births. The prevalence varied among the various registers. The mean prevalence among LB in all registers for T13 was 0.55 (95%CI 0.38-0.72), and for T18 was 1.07 (95% CI 0.77-1.38), per 10,000 births. The median mortality in the first week of life was 48% for T13 and 42% for T18, across all registers, half of which occurred on the first day of life. Across 16 registers with complete 1-year follow-up, mortality in first year of life was 87% for T13 and 88% for T18. This study provides an international perspective on prevalence and mortality of T13 and T18. Overall outcomes and survival among LB were poor with about half of live born infants not surviving first week of life; nevertheless about 10% survived the first year of life. Prevalence and outcomes varied by country and termination policies. The study highlights the variation in screening, data collection, and reporting practices for these conditions. © 2019 Wiley Periodicals, Inc. KEYWORDS: Edwards syndrome; Patau syndrome; congenital anomaly register; trisomies; trisomy 13; trisomy 18 PMID: 31566869 PMCID: PMC6848757 DOI: 10.1002/ajmg.a.61365
Bilateral Wilms'Tumor in Trisomy 18 Syndrome: Case Report and Critical Review of the Literature
Ann Clin Lab Sci. 2018 May;48(3):369-372.
Sergi C1,2,3,4, Kos M5,6.
We present a patient with trisomy 18 syndrome and bilateral Wilms' tumor representing the second case of the literature. Physicians should remain alert to the possibility of WT in patients with trisomy 18 who may survive beyond infancy. In this event, it may be essential to consider periodic abdominal ultrasound for screening purposes. A critical review of the literature is presented. KEYWORDS: karyotype; nephroblastoma; trisomy 18 PMID: 29970442
Fetal fraction-based risk algorithm for non-invasive prenatal testing: screening for trisomy 13, 18, and triploidy in women with low cell-free fetal DNA
Ultrasound Obstet Gynecol. 2018 Jul 16. doi: 10.1002/uog.19176. [Epub ahead of print]
McKanna T1, Ryan A1, Krinshpun S1, Kareht S1, Marchand K2, Grabarits C3, Ali M4, McElheny A5, Gardiner K6, LeChien K7, Hsu M8, Saltzman D9, Stosic M1, Martin K1, Benn P10.
OBJECTIVE: To identify pregnancies at increased risk for trisomy 13, trisomy 18, and triploidy attributable to low fetal fraction (FF). METHODS: A FF-based risk (FFBR) model was built using data from >165,000 singleton pregnancies referred for SNP-based non-invasive prenatal testing (NIPT). Based on maternal weight and gestational age, FF distributions for normal, trisomy 13, trisomy 18, and triploid pregnancies were constructed and used to adjust prior risks for these abnormalities. A risk cutoff of ≥1% was chosen to define pregnancies at high risk for trisomy 13, trisomy 18, or triploidy (i.e., a high FFBR score). The model was evaluated on an independent blinded set of pregnancies for which SNP-based NIPT did not return a result, and for which retrospectively gathered pregnancy outcome information was available. RESULTS: The evaluation cohort comprised 1,148 cases, of which approximately half received a high FFBR score. Compared with incidence rates expected based on maternal age (MA) and gestational age (GA), cases with a high FFBR score had a significantly increased rate of trisomy 13, trisomy 18, or triploidy combined (5.7% vs. 0.7%; p<0.001) and of unexplained pregnancy loss (14.7% vs 10.4% p<0.001). For cases that did not receive a high FFBR score, the incidence of a chromosome abnormality or loss was not significantly different than that expected based on MA and GA. In the study cohort, the sensitivity of the FFBR model for detection of trisomy 13, trisomy 18, or triploidy was 91.4% (95% CI: 76.9-98.2) with a positive predictive value of 5.7% (32/564; 95% CI: 3.9-7.9). CONCLUSIONS: For pregnancies with a FF too low to receive a result on standard NIPT, the FFBR algorithm can identify a subset of cases at increased risk for trisomy 13, trisomy 18, or triploidy. For the remainder of cases, the risk for a fetal chromosome abnormality was unchanged. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved. KEYWORDS: NIPT; fetal fraction; guidelines; maternal weight; pregnancy loss; prenatal screening; triploidy; trisomy PMID: 30014528 DOI: 10.1002/uog.19176
Enhanced First Trimester Aneuploidy Screening with Placental Growth Factor and Alpha Feto-Protein: Detection of Trisomies 18 and 13
J Obstet Gynaecol Can. 2018 Jul 16. pii: S1701-2163(18)30005-7. doi: 10.1016/j.jogc.2018.01.007. [Epub ahead of print]
Huang T1, Meschino WS2, Rashid S3, Dennis A3, Mak-Tam E3, Cuckle H4. Author information Abstract OBJECTIVES: To assess the performance of first trimester combined screening (FTS) when enhanced with placental growth factor and alpha feto-protein in the detection of trisomies 18 and 13. METHODS: A retrospective case-control study. Marker parameters were derived using frozen serum samples. Multivariate Gaussian modelling predicted the detection rate (DR) and false-positive rate (FPR) for trisomies 18 and 13 with FTS and enhanced first trimester screening (eFTS) using the risk of trisomy 21 alone and an additional risk cut-off for trisomy 18, or trisomies 18 or 13. RESULTS: There were 83 trisomy 18, 22 trisomy 13, and 588 controls. The median placental growth factor levels in trisomies 18 and 13 were 0.75 and 0.65 multiple of the median of controls, respectively (both P <0.0001). There were no statistically significant differences in alpha feto-protein levels. Modelling predicts that using a trisomy 21 risk cut-off alone, at FPR of 3%, eFTS increases the DR for trisomies 18 and 13 by 0.6-0.8% compared with FTS. Additionally using a trisomy 18 risk cut-off, at an extra FPR of 0.2%, eFTS increased the DR by 0.6-0.9% over FTS; using a trisomy 18 or 13 risk cut-off did not further increase detection for FTS or eFTS. The increase in DR was greater at higher FPR. CONCLUSION: eFTS increases the detection of trisomies 18 and 13 to a small extent. Copyright © 2018 Society of Obstetricians and Gynaecologists of Canada. Published by Elsevier Inc. All rights reserved. KEYWORDS: First trimester; alpha feto-protein; placental growth factor; screening; trisomy 13; trisomy 18 PMID: 30025867 DOI: 10.1016/j.jogc.2018.01.007
Fetal outcome of trisomy 18 diagnosed after 22 weeks of gestation: Experience of 123 cases at a single perinatal center
Congenit Anom (Kyoto). 2016 Jan;56(1):35-40. doi: 10.1111/cga.12118.
Nagase H1,2, Ishikawa H1, Toyoshima K3, Itani Y3, Furuya N4, Kurosawa K5, Hirahara F2, Yamanaka M6.
To investigate the pregnancy outcome of the fetuses with trisomy 18, we studied 123 cases of trisomy 18 who were born at our hospital from 1993 to 2009. Among them, 95.9% were diagnosed with trisomy 18 prenatally. Prenatal ultrasound findings showed fetal growth restriction in 77.2%, polyhydramnios in 63.4% and congenital heart defects in 95.1%. For 18 cases, cesarean section (C-section) was chosen, and for 75 cases, transvaginal delivery was chosen. Premature delivery occurred in 35.5%. Stillbirths occurred in 50 cases (40.7%). Fetal demise before onset of labor occurred in 30 cases and fetal demise during labor occurred in 20 cases which was 26.7% of vaginal deliveries. Among the 73 live-born infants, the survival rate for 24 h, 1 week, 1 month and 1 year were 63%, 43%, 33% and 3%. The median survival time was 3.5 days. There was no significant difference between the survival time of C-section and that of vaginal delivery. However, for the births involving breech presentation, the survival time of C-section was significantly longer than that of vaginal delivery. When the fetus is diagnosed with trisomy 18, the parents have to make many choices. These findings constitute critical information in prenatal counseling to the couples whose fetuses have been found to have trisomy 18, especially when they choose palliative approaches in the perinatal management. © 2015 Japanese Teratology Society. KEYWORDS: management; palliative care; prenatal ultrasound findings; prognosis; trisomy 18
- Fetal outcome of trisomy 18 diagnosed after 22 weeks of gestation: Experience of 123 cases at a single perinatal center
- 123 cases (1993 to 2009) 95.9% prenatal diagnosis
- ultrasound - fetal growth restriction in 77.2%, polyhydramnios in 63.4% and congenital heart defects in 95.1%.
- 18 cases, cesarean section (C-section)
- 75 cases, transvaginal delivery Premature delivery occurred in 35.5%.
- Stillbirths occurred in 50 cases (40.7%).
- Fetal demise before onset of labor in 30 cases and fetal demise during labor in 20 cases which was 26.7% of vaginal deliveries.
- 73 live-born infants, the survival rate for 24 h, 1 week, 1 month and 1 year were 63%, 43%, 33% and 3%. The median survival time was 3.5 days."
- SOFT USA Support Organization For Trisomy 18, 13, and Related Disorders
- SOFT UK Support Organisation for trisomy 13/18 and related disorders
- Trisomy 18 Foundation, Inc.
- Trisomy 18 Support Program
- The Chromosome 18 Registry & Research Society
- Perinatal Hospice Care - Preparing for birth and death”
- Humpath #5389
The trisomy 18 syndrome
Orphanet J Rare Dis. 2012 Oct 23;7(1):81. [Epub ahead of print]
Cereda A, Carey JC.
The trisomy 18 syndrome, also known as Edwards syndrome, is a common chromosomal disorder due to the presence of an extra chromosome 18, either full, mosaic trisomy, or partial trisomy 18q. The condition is the second most common autosomal trisomy syndrome after trisomy 21. The live born prevalence is estimated as 1/6,000-1/8,000, but the overall prevalence is higher (1/2500-1/2600) due to the high frequency of fetal loss and pregnancy termination after prenatal diagnosis. The prevalence of trisomy 18 rises with the increasing maternal age. The recurrence risk for a family with a child with full trisomy 18 is about 1%.Currently most cases of trisomy 18 are prenatally diagnosed, based on screening by maternal age, maternal serum marker screening, or detection of sonographic abnormalities (e.g., increased nuchal translucency thickness, growth retardation, choroid plexus cyst, overlapping of fingers, and congenital heart defects ). The recognizable syndrome pattern consists of major and minor anomalies, prenatal and postnatal growth deficiency, an increased risk of neonatal and infant mortality, and marked psychomotor and cognitive disability. Typical minor anomalies include characteristic craniofacial features, clenched fist with overriding fingers, small fingernails, underdeveloped thumbs, and short sternum. The presence of major malformations is common, and the most frequent are heart and kidney anomalies. Feeding problems occur consistently and may require enteral nutrition.Despite the well known infant mortality, approximately 50% of babies with trisomy 18 live longer than 1 week and about 5-10% of children beyond the first year. The major causes of death include central apnea, cardiac failure due to cardiac malformations, respiratory insufficiency due to hypoventilation, aspiration, or upper airway obstruction and, likely, the combination of these and other factors (including decisions regarding aggressive care). Upper airway obstruction is likely more common than previously realized and should be investigated when full care is opted by the family and medical team.The complexity and the severity of the clinical presentation at birth and the high neonatal and infant mortality make the perinatal and neonatal management of babies with trisomy 18 particularly challenging, controversial, and unique among multiple congenital anomaly syndromes. Health supervision should be diligent, especially in the first 12 months of life, and can require multiple pediatric and specialist evaluations.
|Frequency||Organ/System||Prevalent type of malformation|
|Common (>75%)||heart||septal defects, patent ductus arteriosus, and polyvalvular disease|
|Frequent (25-75%)||genitourinary||horseshoe kidney|
|Less frequent (5-25%)||gastrointestinal
central nervous system
|omphalocele, esophageal atresia with tracheo-esophageal fistula, pyloric stenosis, Meckel diverticulum
cerebellar hypoplasia, agenesis of corpus callosum, polymicrogyria, spina bifida
microphthalmia, coloboma, cataract, corneal opacities
J Am Coll Cardiol. 1989 Jun;13(7):1586-97. Cardiac malformations in trisomy-18: a study of 41 postmortem cases. Van Praagh S1, Truman T, Firpo A, Bano-Rodrigo A, Fried R, McManus B, Engle MA, Van Praagh R. Author information Abstract The cardiac malformations in 41 karyotyped and autopsy cases of trisomy-18 are presented in detail. The salient findings were a ventricular septal defect in all cases; tricuspid valve anomalies in 33 cases (80%); pulmonary valve anomalies in 30 (70%); aortic valve malformations in 28 (68%); mitral valve anomalies in 27 (66%); polyvalvular disease (that is, malformations of more than one valve) in 38 (93%); a subpulmonary infundibulum (conus) in 40 (98%); a bilateral conus with a short subaortic infundibulum in 1 case with double outlet right ventricle (this being the only documented case of bilateral infundibulum in trisomy-18); double outlet right ventricle in 4 cases (10%), three having a subpulmonary infundibulum only and all 4 having mitral atresia; tetralogy of Fallot in 6 cases (15%), 2 having pulmonary atresia; and a striking absence of transposition of the great arteries and inversion at any level (visceral or cardiac), findings that appear to be characteristic of all trisomies. These data suggest that excessive chromosomal material (as in trisomies) may result in situs solitus at all levels. The malformations of the atrioventricular and semilunar valves were characterized by redundant or thick myxomatous leaflets, long chordae tendineae and hypoplastic or absent papillary muscles. The ventricular septal defect was associated with anterosuperior conal septal malalignment in 25 cases (61%). On the basis of the characteristic valvular lesions, the type of ventricular septal defect and the absence of transposition or inversions, two-dimensional echocardiographic diagnosis of trisomy-18 in the fetus may become possible. PMID: 2723271
The cardiac malformations in 41 karyotyped and autopsy cases of trisomy-18 are presented in detail. The salient findings were a ventricular septal defect in all cases; tricuspid valve anomalies in 33 cases (80%); pulmonary valve anomalies in 30 (70%); aortic valve malformations in 28 (68%); mitral valve anomalies in 27 (66%); polyvalvular disease (that is, malformations of more than one valve) in 38 (93%); a subpulmonary infundibulum (conus) in 40 (98%); a bilateral conus with a short subaortic infundibulum in 1 case with double outlet right ventricle (this being the only documented case of bilateral infundibulum in trisomy-18); double outlet right ventricle in 4 cases (10%), three having a subpulmonary infundibulum only and all 4 having mitral atresia; tetralogy of Fallot in 6 cases (15%), 2 having pulmonary atresia; and a striking absence of transposition of the great arteries and inversion at any level (visceral or cardiac), findings that appear to be characteristic of all trisomies.