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]

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: Introduction | Genetic risk maternal age | Trisomy 21 | Trisomy 18 | Trisomy 13 | Trisomy X | Monosomy | Fragile X | Williams | Alagille | Philadelphia chromosome | Hydatidiform Mole | Prenatal Diagnosis | Neonatal Diagnosis | International Classification of Diseases | Molecular Development - 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.
  • References appear in 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.

Links: References | Discussion Page | Pubmed Most Recent | Journal Searches


Search term: Trisomy 18

Fuman She, Shengwen Dong, Bibo Yuan, Xiaoli Gao Diagnosis of fetal megacystis with chromosomal abnormality by 2D prenatal ultrasound: A case report. Medicine (Baltimore): 2017, 96(46);e8589 PubMed 29145274

Mylène Badeau, Carmen Lindsay, Jonatan Blais, Leon Nshimyumukiza, Yemisi Takwoingi, Sylvie Langlois, France Légaré, Yves Giguère, Alexis F Turgeon, William Witteman, François Rousseau Genomics-based non-invasive prenatal testing for detection of fetal chromosomal aneuploidy in pregnant women. Cochrane Database Syst Rev: 2017, 11;CD011767 PubMed 29125628

Sun Kyung Hoon, Seung-Woo Kang, Sang-Hyun Kwak, Joungmin Kim Hypoxia due to positive pressure ventilation in Edwards' syndrome: A case report. J. Int. Med. Res.: 2017;300060517734680 PubMed 29125001

Jiexia Yang, Yiming Qi, Fangfang Guo, Yaping Hou, Haishan Peng, Dongmei Wang, Haoxin Oy, Aihua Yin A case of placental trisomy 18 mosaicism causing a false negative NIPT result. Mol Cytogenet: 2017, 10;40 PubMed 29093756

Sylvie Langlois, JoAnn Johnson, François Audibert, Jean Gekas, Jean Claude Forest, André Caron, Keli Harrington, Melanie Pastuck, Hasna Meddour, Amélie Tétu, Julian Little, François Rousseau Comparison of first tier cell-free DNA screening for common aneuploidies with conventional publically funded screening. Prenat. Diagn.: 2017; PubMed 29080223


Survival Rate

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

Survival rate from a Japanese study of 73 live-born infants.[5]

Time Percentage
24 h 63%
1 week 43%
1 month 33%
1 year 3%

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. J H EDWARDS, D G HARNDEN, A H CAMERON, V M CROSSE, O H WOLFF A new trisomic syndrome. Lancet: 1960, 1(7128);787-90 PubMed 13819419
  2. K PATAU, D W SMITH, E THERMAN, S L INHORN, H P WAGNER Multiple congenital anomaly caused by an extra autosome. Lancet: 1960, 1(7128);790-3 PubMed 14430807
  3. D W SMITH, K PATAU, E THERMAN, S L INHORN A new autosomal trisomy syndrome: multiple congenital anomalies caused by an extra chromosome. J. Pediatr.: 1960, 57;338-45 PubMed 13831938
  4. Katherine E Nelson, Kari R Hexem, Chris Feudtner Inpatient hospital care of children with trisomy 13 and trisomy 18 in the United States. Pediatrics: 2012, 129(5);869-76 PubMed 22492767
  5. 5.0 5.1 5.2 Hiromi Nagase, Hiroshi Ishikawa, Katsuaki Toyoshima, Yasufumi Itani, Noritaka Furuya, Kenji Kurosawa, Fumiki Hirahara, Michiko Yamanaka Fetal outcome of trisomy 18 diagnosed after 22 weeks of gestation: Experience of 123 cases at a single perinatal center. Congenit Anom (Kyoto): 2015; PubMed 26104883
  6. 6.0 6.1 Anna Cereda, John C Carey The trisomy 18 syndrome. Orphanet J Rare Dis: 2012, 7;81 PubMed 23088440 | Orphanet J Rare Dis.
  7. David T Miller, Margaret P Adam, Swaroop Aradhya, Leslie G Biesecker, Arthur R Brothman, Nigel P Carter, Deanna M Church, John A Crolla, Evan E Eichler, Charles J Epstein, W Andrew Faucett, Lars Feuk, Jan M Friedman, Ada Hamosh, Laird Jackson, Erin B Kaminsky, Klaas Kok, Ian D Krantz, Robert M Kuhn, Charles Lee, James M Ostell, Carla Rosenberg, Stephen W Scherer, Nancy B Spinner, Dimitri J Stavropoulos, James H Tepperberg, Erik C Thorland, Joris R Vermeesch, Darrel J Waggoner, Michael S Watson, Christa Lese Martin, David H Ledbetter Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am. J. Hum. Genet.: 2010, 86(5);749-64 PubMed 20466091
  8. Alexander Egbe, Simon Lee, Deborah Ho, Santosh Uppu, Shubhika Srivastava Prevalence of congenital anomalies in newborns with congenital heart disease diagnosis. Ann Pediatr Cardiol: 2014, 7(2);86-91 PubMed 24987252 | Ann Pediatr Cardiol.

Reviews

Anna Cereda, John C Carey The trisomy 18 syndrome. Orphanet J Rare Dis: 2012, 7;81 PubMed 23088440


Articles

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Cite this page: Hill, M.A. 2017 Embryology Trisomy 18. Retrieved November 18, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/Trisomy_18

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