Trisomy 18

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Chromosome- trisomy 18.jpg

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[1][2][3] and named after one of the key authors, John Hilton Edwards.[1]

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[4], see also the recent Japanese study.[5]

International Classification of Diseases: Q91 Edwards' syndrome and Patau's syndrome


Genetic Links: genetic abnormalities | Genetic risk maternal age | Trisomy 21 | Trisomy 18 | Trisomy 13 | Trisomy X | Monosomy | Fragile X | Williams | Alagille | Philadelphia chromosome | mitochondria | hydatidiform mole | epigenetics | Prenatal Diagnosis | Neonatal Diagnosis | meiosis | mitosis | International Classification of Diseases | genetics

Some Recent Findings

  • Fetal outcome of trisomy 18 diagnosed after 22 weeks of gestation: Experience of 123 cases at a single perinatal center[5] "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.[6] "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[7]
More recent papers  
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This table shows an automated computer PubMed search using the listed sub-heading term.

  • Therefore the list of references do not reflect any editorial selection of material based on content or relevance.
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Search term: Trisomy 18

Wencheng Dai, Yulin Jiang, Mijiti Gulinazi, Xuan Liu, Zhen Yu, Ning Liu, Lixia Wang, Guangjuan Ma [Application for prenatal diagnosis using both chromosomal karyotype analysis and BACs-on-Beads assay]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi: 2018, 35(3);357-360 PubMed 29896731

Anna Keravnou, Marios Ioannides, Charalambos Loizides, Kyriakos Tsangaras, Achilleas Achilleos, Petros Mina, Elena Kypri, Michael D Hadjidaniel, Maria Neofytou, Skevi Kyriacou, Carolina Sismani, George Koumbaris, Philippos C Patsalis MeDIP combined with in-solution targeted enrichment followed by NGS: Inter-individual methylation variability of fetal-specific biomarkers and their implementation in a proof of concept study for NIPT. PLoS ONE: 2018, 13(6);e0199010 PubMed 29889893

Kaixuan Xing, Yazhou Cui, Jing Luan, Xiaoyan Zhou, Liang Shi, Jinxiang Han Establishment of a human trisomy 18 induced pluripotent stem cell line from amniotic fluid cells. Intractable Rare Dis Res: 2018, 7(2);94-99 PubMed 29862150

Wei Tang Modeling the rare diseases process in dish. Intractable Rare Dis Res: 2018, 7(2);72 PubMed 29862146

Jing Wang, Lin Chen, Cong Zhou, Li Wang, Hanbin Xie, Yuanyuan Xiao, Hongmei Zhu, Ting Hu, Zhu Zhang, Qian Zhu, Zhiying Liu, Shanlin Liu, He Wang, Mengnan Xu, Zhilin Ren, Fuli Yu, David S Cram, Hongqian Liu Prospective chromosome analysis of 3429 amniocentesis samples in China using copy number variation sequencing. Am. J. Obstet. Gynecol.: 2018; PubMed 29852155


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.[5]


Prevalence

Syndrome abnormalities USA 1998-2008 graph.jpg

Abnormalities from USA Nationwide Inpatient Sample database (1998 to 2008)[8]

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[6]

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

Karyotyping

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

  1. 1.0 1.1 EDWARDS JH, HARNDEN DG, CAMERON AH, CROSSE VM & WOLFF OH. (1960). A new trisomic syndrome. Lancet , 1, 787-90. PMID: 13819419
  2. PATAU K, SMITH DW, THERMAN E, INHORN SL & WAGNER HP. (1960). Multiple congenital anomaly caused by an extra autosome. Lancet , 1, 790-3. PMID: 14430807
  3. SMITH DW, PATAU K, THERMAN E & INHORN SL. (1960). A new autosomal trisomy syndrome: multiple congenital anomalies caused by an extra chromosome. J. Pediatr. , 57, 338-45. PMID: 13831938
  4. Nelson KE, Hexem KR & Feudtner C. (2012). Inpatient hospital care of children with trisomy 13 and trisomy 18 in the United States. Pediatrics , 129, 869-76. PMID: 22492767 DOI.
  5. 5.0 5.1 5.2 Nagase H, Ishikawa H, Toyoshima K, Itani Y, Furuya N, Kurosawa K, Hirahara F & Yamanaka M. (2016). Fetal outcome of trisomy 18 diagnosed after 22 weeks of gestation: Experience of 123 cases at a single perinatal center. Congenit Anom (Kyoto) , 56, 35-40. PMID: 26104883 DOI.
  6. 6.0 6.1 Cereda A & Carey JC. (2012). The trisomy 18 syndrome. Orphanet J Rare Dis , 7, 81. PMID: 23088440 DOI.
  7. Miller DT, Adam MP, Aradhya S, Biesecker LG, Brothman AR, Carter NP, Church DM, Crolla JA, Eichler EE, Epstein CJ, Faucett WA, Feuk L, Friedman JM, Hamosh A, Jackson L, Kaminsky EB, Kok K, Krantz ID, Kuhn RM, Lee C, Ostell JM, Rosenberg C, Scherer SW, Spinner NB, Stavropoulos DJ, Tepperberg JH, Thorland EC, Vermeesch JR, Waggoner DJ, Watson MS, Martin CL & Ledbetter DH. (2010). Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am. J. Hum. Genet. , 86, 749-64. PMID: 20466091 DOI.
  8. Egbe A, Lee S, Ho D, Uppu S & Srivastava S. (2014). Prevalence of congenital anomalies in newborns with congenital heart disease diagnosis. Ann Pediatr Cardiol , 7, 86-91. PMID: 24987252 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

Articles

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Cite this page: Hill, M.A. (2018, June 22) Embryology Trisomy 18. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Trisomy_18

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