Trisomy 18

Embryology - 2 Dec 2023        Expand to Translate
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LD40.2 Complete Trisomy 18

ICD-11 - LD40.2 Complete trisomy 18 Trisomy 18 is a chromosomal abnormality associated with the presence of an extra chromosome 18 and characterized by growth delay, dolichocephaly, a characteristic facies, limb anomalies and visceral malformations.

Introduction

Karyotype Trisomy 18 male

Q91 Edwards' syndrome and Patau's syndrome (ICD-11 beta) - LC20.3 Complete trisomy 18

(Edwards Syndrome, 18T) An aneuploidy, first recognized as a specific clinical entity by the discovery of an extra chromosome 18 in babies with a particular pattern of malformation by independent groups and named after one of the key authors, John Hilton Edwards.

In many cases associated abnormalities include: fetal growth restriction, polyhydramnios and congenital heart defects.

Both trisomy 13 and trisomy 18 are generally considered fatal anomalies, with a majority of infants dying in the first year after birth, see also the recent Japanese study.

Some Recent Findings

Trisomy 13 and Trisomy 18-Prevalence and mortality-A multi-registry population based analysis "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. Solid tumor screening recommendations in trisomy 18 "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." Sensitivity of prenatal ultrasound for detection of Trisomy 18 "To evaluate the sensitivity of prenatal ultrasound (US) for trisomy (T18) diagnosis and describe US findings in a large tertiary care institution in the USA. Materials and methods: This was a retrospective cohort of all T18 cases diagnosed at our institution from October 2004 to October 2014 based on prenatal or postnatal genetic diagnostic testing. We included all women with a fetus affected by T18 who had a comprehensive US by a maternal-fetal medicine specialist performed at our institution. US findings were reviewed, classified by organ system, and categorized as an anomaly or soft marker. Chi-square or t-test was used for statistical analysis. Results: We included 128 cases of T18 with confirmed cytogenetic analysis -110 (86%) of which were diagnosed prenatally or suspected by cell-free DNA and confirmed postnatally, and 18 of which underwent neonatal blood sampling alone. One hundred and twenty-one (95%) had at least one abnormal US finding. Anomalies were more frequently identified on US at ≥20 weeks as compared with <20 weeks (93% versus 76%; p = .004). The mean number of findings detected per fetus was 5.1 ± 3.0. Fetuses diagnosed by postnatal sampling alone had a similar number of US exams performed and number of abnormal findings compared to those diagnosed prenatally. Conclusion: Ninety-five percent of fetuses with T18 had at least one abnormal US finding. This sensitivity of is higher than reported in most prior studies, but is not 100%, and should be considered when counseling women regarding prenatal diagnosis of T18. Rationale: Historical detection rates for abnormal sonographic findings in trisomy 18 fetuses range from 70% to 100%. These studies are limited by small sample sizes. This is a contemporary study of ultrasound findings in a large group of women with confirmed trisomy 18 by prenatal or postnatal genetic diagnosis. We provide expansive detail on soft markers and anomalies broken down by organ-system and gestational age."

More recent papers

This table allows an automated computer search of the external PubMed database using the listed "Search term" text link. This search now requires a manual link as the original PubMed extension has been disabled. The displayed list of references do not reflect any editorial selection of material based on content or relevance. References also appear on this list based upon the date of the actual page viewing. References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability. More? References | Discussion Page | Journal Searches | 2019 References | 2020 References Search term: Trisomy 18 | Edwards Syndrome

Older papers

These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table. See also the Discussion Page for other references listed by year and References on this current page. Fetal outcome of trisomy 18 diagnosed after 22 weeks of gestation: Experience of 123 cases at a single perinatal center "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." Recent Trisomy 18 Review. "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). " Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies

Survival Rate

Stillbirths occurs prenatally in 40% cases with fetal demise also occurring before and during onset of labor.

Trisomy 18 Survival Rate

Time	Percentage
24 h	63%
1 week	43%
1 month	33%
1 year	3%
Survival rate from a Japanese study of 73 live-born infants.    Trisomy 18

Prevalence

Abnormalities from USA Nationwide Inpatient Sample database (1998 to 2008)

Features

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 craniofacial eye limb	omphalocele, esophageal atresia with tracheo-esophageal fistula, pyloric stenosis, Meckel diverticulum cerebellar hypoplasia, agenesis of corpus callosum, polymicrogyria, spina bifida orofacial clefts microphthalmia, coloboma, cataract, corneal opacities radial aplasia/hypoplasia
Table modified from

Pedbase Entry

Definition

A chromosomal disorder resulting in a syndrome characterized by specific (small) dysmorphic features and organ malformations.

Epidemiology

incidence: 1/8000 live births most die in embryonic or fetal life 2nd most common autosomal aberration 2nd most common multiple malformation syndrome age of onset: newborn risk factors: advanced maternal age F > M (4:1)

History

1960 first recognized as a specific clinical entity by the discovery of an extra chromosome 18 in babies with a particular pattern of malformation by three independent groups (Edwards et al., Patau et al., Smith et al.)

Pathogenesis - Genetics

Trisomy 18

90% of cases due to meiotic nondisjunction less than 1% recurrence rate

Mosaicism

10% of cases due to postzygotic (postfertilization) mitotic nondisjunction leads to the partial clinical expression of Trisomy 18 with a longer survival

Translocations

very rare give rise to partial trisomy 18 syndromes short arm: causes non-specific clinical features with mild or no mental deficiency long arm: entire: clinically indistinguishable from trisomy 18 distal 1/3 -> : partial clinical picture of trisomy 18 with a longer survival and less profound mental retardation

Clinical Features

Dysmorphic Features

1. Facial

• microcephaly with prominent occiput
• narrow bifrontal diameter
• short palpabral fissures
• low-set malformed ears
• cleft lip +/- palate
• narrow palatal arch
• micrognathia

2. Skeletal

• neck - webbed
• chest - short sternum, widely spaced nipples
• hips - small pelvis, congenital dislocation of the hips, limited hip abduction
• extremities - phocomelia, rockerbottom feet or equinovarus, short dorsiflexed big toes, fixed flexion deformity of the fingers (overlapping of the 2nd and 5th fingers over the 3rd and 4th fingers), simple arch pattern of the fingers and toes, hypoplasia of fingernails, single crease of 5th finger or all fingers (absence of interphalangeal flexion creases), simian crease

Organ Malformations

1. Central Nervous System

• severe mental retardation
• hypotonia -> hypertonia
• neural tube defects
• poor suck and weak cry
• failure to thrive
• ocular anomalies

2. Respiratory

• apnea

3. Cardiovascular( >95%)

• major: VSD, ASD, PDA
• minor: transposition, ToF, coarctation, anomalous coronary artery, dextrocardia, aberrant subclavian artery, arteriosclerosis, PS, bicuspid aortic and/or pulmonic valves

4. Gastrointestinal

• inguinal, umbilical, and/or diaphragmatic hernia
• congenital defects: diastasis recti, heterotopic pancreas, malrotation, Meckel's, tracheoesophageal fistula

5. Genitourinary

• cryptorchidism
• congenital defects: double ureter, ectopic kidney, horseshoe kidney, hydronephrosis, polycystic kidney

Investigations

Imaging Studies

• to rule out organ malformations:
• cardiovascular anomalies - Echo
• gastrointestinal anomalies - Barium Swallow, Endoscope
• genitourinary anomalies - Ultrasound

Management

Supportive, very poor prognosis.

• 30% dying by 1 month of age
• 50% dying by 2 months of age
• 90% dying by 12 months of age

Genetic counselling, recurrence rate depends on genotype.

(modified from original 1999 Pedbase entry)

References

Articles

Mudaliyar US & Mudaliyar SU. (2017). Strawberry skull in Edwards syndrome. BJR Case Rep , 3, 20170045. PMID: 30363185 DOI.

Reviews

Satgé D, Nishi M, Sirvent N & Vekemans M. (2016). A tumor profile in Edwards syndrome (trisomy 18). Am J Med Genet C Semin Med Genet , 172, 296-306. PMID: 27474103 DOI.

Roberts W, Zurada A, Zurada-ZieliŃSka A, Gielecki J & Loukas M. (2016). Anatomy of trisomy 18. Clin Anat , 29, 628-32. PMID: 27087248 DOI.

Janvier A, Farlow B & Barrington K. (2016). Cardiac surgery for children with trisomies 13 and 18: Where are we now?. Semin. Perinatol. , 40, 254-60. PMID: 26847083 DOI.

Cereda A & Carey JC. (2012). The trisomy 18 syndrome. Orphanet J Rare Dis , 7, 81. PMID: 23088440 DOI.

Rosa RF, Rosa RC, Zen PR, Graziadio C & Paskulin GA. (2013). Trisomy 18: review of the clinical, etiologic, prognostic, and ethical aspects. Rev Paul Pediatr , 31, 111-20. PMID: 23703053

Search Pubmed

Search Pubmed: trisomy 13 | Edwards Syndrome

External Links

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• Medlineplus - Trisomy 18
• Trisomy 18 Organization
• Better Health Victoria - trisomy disorders
• SOFT USA Support Organization For Trisomy 18, 13, and Related Disorders
• SOFT UK Support Organisation for trisomy 13/18 and related disorders
• Trisomy 18 Support Program
• The Chromosome 18 Registry & Research Society

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Cite this page: Hill, M.A. (2023, December 2) Embryology Trisomy 18. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Trisomy_18

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© Dr Mark Hill 2023, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G