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Trisomy 18

August 28, 2023

Trisomy 18, also known as Edwards syndrome, is a genetic disorder caused by the presence of a third copy of all or part of chromosome 18.[3] Many parts of the body are affected.[3] Babies are often born small and have heart defects.[3] Other features include a small head, small jaw, clenched fists with overlapping fingers, and severe intellectual disability.[3]

Trisomy 18
Other namesTrisomy 18 (T18[1]), chromosome 18 duplication,[2] trisomy E syndrome[3]
Infant with trisomy 18
SpecialtyMedical genetics, pediatrics
SymptomsSmall head, small jaw, clenched fists with overlapping fingers, profound intellectual disability[3]
ComplicationsHeart defects[3]
Usual onsetPresent at birth[3]
CausesThird copy of chromosome 18 (usually new mutation)[3]
Risk factorsOlder mother[3]
Diagnostic methodUltrasound, amniocentesis[2]
TreatmentSupportive care[2]
Prognosis5–10% survive past a year old[3]
Frequency1 per 5,000 births[3]

Most cases of trisomy 18 occur due to problems during the formation of the reproductive cells or during early development.[3] The chance of this condition occurring increases with the mother's age.[3] Rarely, cases may be inherited.[3] Occasionally, not all cells have the extra chromosome, known as mosaic trisomy, and symptoms in these cases may be less severe.[3] An ultrasound during pregnancy can increase suspicion for the condition, which can be confirmed by amniocentesis.[2]

Treatment is supportive.[2] After having one child with the condition, the risk of having a second is typically around one percent.[2] It is the second-most common condition due to a third chromosome at birth, after Down syndrome.[4]

Trisomy 18 occurs in around 1 in 5,000 live births.[3] Many of those affected die before birth.[3] Some studies suggest that more babies that survive to birth are female.[2] Survival beyond a year of life is around 5–10%.[3] It is named after English geneticist John Hilton Edwards, who first described the syndrome in 1960.[5]

Signs and symptoms Edit

 
Clenched hand and overlapping fingers: index finger overlaps third finger and fifth finger overlaps fourth finger, characteristically seen in trisomy 18. This is caused by congenital joint contracture.[6]

Children born with Edwards' syndrome may have some or all of these characteristics: kidney malformations, structural heart defects at birth (i.e., ventricular septal defect, atrial septal defect, patent ductus arteriosus), intestines protruding outside the body (omphalocele), esophageal atresia, intellectual disability, developmental delays, growth deficiency, feeding difficulties, breathing difficulties, and arthrogryposis (a muscle disorder that causes multiple joint contractures at birth).[7][8]

Some physical malformations associated with Edwards' syndrome include small head (microcephaly) accompanied by a prominent back portion of the head (occiput), low-set, malformed ears, abnormally small jaw (micrognathia), cleft lip/cleft palate, upturned nose, narrow eyelid openings (blepharophimosis), widely spaced eyes (ocular hypertelorism), drooping of the upper eyelids (ptosis), a short breast bone, clenched hands, choroid plexus cysts, underdeveloped thumbs and/or nails, absent radius, webbing of the second and third toes, clubfoot or rocker bottom feet, and in males, undescended testicles.[7][8]

In utero, the most common characteristic is cardiac anomalies, followed by central nervous system anomalies such as head shape abnormalities. The most common intracranial anomaly is the presence of choroid plexus cysts, which are pockets of fluid on the brain. These are not problematic in themselves, but their presence may be a marker for trisomy 18.[9][10] Sometimes, excess amniotic fluid or polyhydramnios is exhibited.[7] Although uncommon in the syndrome, trisomy 18 causes a large portion of prenatally diagnosed cases of Dandy–Walker malformation.[11][12]

Genetics Edit

 
Karyotype of a person with trisomy 18. Three copies of the Chromosome 18 are detected.

Trisomy 18 is a chromosomal abnormality characterized by the presence of an extra copy of genetic material on the 18th chromosome, either in whole (trisomy 18) or in part (such as due to translocations). The additional chromosome usually occurs before conception. The effects of the extra copy vary greatly, depending on the extent of the extra copy, genetic history, and chance. Trisomy 18 occurs in all human populations, but is more prevalent in female offspring.[13]

A typical egg or sperm cell contains individual chromosomes, each of which contributes to the 23 pairs of chromosomes needed to form a normal cell with a typical human karyotype of 46 chromosomes. Numerical errors can arise at either of the two meiotic divisions and cause the failure of a chromosome to segregate into the daughter cells (nondisjunction). This results in an extra chromosome, making the haploid number 24 rather than 23. Fertilization of eggs or insemination by sperm that contain an extra chromosome results in trisomy, or three copies of a chromosome rather than two.[14]

Trisomy 18 (47,XX,+18) is caused by a meiotic nondisjunction event. With nondisjunction, a gamete (i.e., a sperm or egg cell) is produced with an extra copy of chromosome 18; the gamete thus has 24 chromosomes. When combined with a normal gamete from the other parent, the embryo has 47 chromosomes, with three copies of chromosome 18.[citation needed]

A small percentage of cases occur when only some of the body's cells have an extra copy of chromosome 18, resulting in a mixed population of cells with a differing number of chromosomes. Such cases are sometimes called mosaic trisomy 18. Very rarely, a piece of chromosome 18 becomes attached to another chromosome (translocated) before or after conception. Affected individuals have two copies of chromosome 18 plus extra material from chromosome 18 attached to another chromosome. With a translocation, a person has a partial trisomy for chromosome 18, and the abnormalities are often less severe than for the typical trisomy 18.[15]

Diagnosis Edit

Ultrasound can increase suspicion for the condition, which can be confirmed by CVS or amniocentesis.[2]

Levels of PAPP-A, AFP, uE3, free β-hCG, all of which are generally decreased during pregnancy.[16]

Prognosis Edit

About 95% of pregnancies that are affected do not result in a live birth.[13] Major causes of death include apnea and heart abnormalities. It is impossible to predict an exact prognosis during pregnancy or the neonatal period.[13] Half of the live infants do not survive beyond the first week of life.[17] The median lifespan is five to 15 days.[18][19] About 8–12% of infants survive longer than 1 year.[20][21][better source needed] One percent of children live to age 10.[13] However, these estimates may be pessimistic; a retrospective Canadian study of 254 children with trisomy 18 demonstrated ten-year survival of 9.8%, and another found that 68.6% of children with surgical intervention survived infancy.[21]

Epidemiology Edit

Trisomy 18 occurs in about 1 in 5,000 live births, but more pregnancies are affected by the syndrome as the majority of those diagnosed with the condition prenatally will not survive to birth.[3] Although women in their 20s and early 30s may conceive babies with trisomy 18, the risk increases with age. The average maternal age for conceiving a child with this disorder is 32.5.[22]

History Edit

Trisomy 18 was first identified by John Hilton Edwards in 1960, although he originally believed it to be caused by a trisomy of chromosome 17.[23] Klaus Patau and Eeva Therman reported another two cases shortly thereafter.[24] They identified the extra chromosome as being part of what Patau's lab called "group E", containing chromosomes 16, 17, and 18, but were unable to determine which chromosome was responsible at the time. Analyzing 5 more cases, they were able to determine that the extra chromosome was in fact chromosome 18.[25]

See also Edit

References Edit

  1. ^ "Edwards' syndrome (T18): Information for parents".
  2. ^ a b c d e f g h "Trisomy 18". Orphanet. May 2008. from the original on 3 October 2016. Retrieved 1 October 2016.
  3. ^ a b c d e f g h i j k l m n o p q r s t "trisomy 18". GHR. March 2012. from the original on 2 October 2016. Retrieved 1 October 2016.
  4. ^ Jorde, Lynn B.; Carey, John C.; Bamshad, Michael J. (2009). Medical Genetics (4 ed.). Elsevier Health Sciences. p. 109. ISBN 978-0323075763. from the original on 2016-10-02.
  5. ^ "Edwards syndrome (John Hilton Edwards)". WhoNamedIt.com. from the original on 2008-07-09. Retrieved 2008-07-24.
  6. ^ Cereda, Anna; Carey, John C (2012-10-23). "The trisomy 18 syndrome". Orphanet Journal of Rare Diseases. 7: 81. doi:10.1186/1750-1172-7-81. ISSN 1750-1172. PMC 3520824. PMID 23088440.
  7. ^ a b c "What is Trisomy 18?". Trisomy 18 Foundation. from the original on 2009-03-23. Retrieved 2008-07-24.
  8. ^ a b "Trisomy 18". Medline. from the original on 2008-10-01. Retrieved 2008-07-24.
  9. ^ Hurt K, Sottner O, Záhumenský J, et al. (2007). "[Choroid plexus cysts and risk of trisomy 18. Modifications regarding maternal age and markers]". Ceska Gynekol (in Czech). 72 (1): 49–52. PMID 17357350.
  10. ^ Papp C, Ban Z, Szigeti Z, Csaba A, Beke A, Papp Z (2007). "Role of second trimester sonography in detecting trisomy 18: a review of 70 cases". J Clin Ultrasound. 35 (2): 68–72. doi:10.1002/jcu.20290. PMID 17206726. S2CID 23836946.
  11. ^ Imataka, George; Yamanouchi, Hideo; Arisaka, Osamu (2007). "Dandy–Walker syndrome and chromosomal abnormalities". Congenital Anomalies. 47 (4): 113–118. doi:10.1111/j.1741-4520.2007.00158.x. ISSN 1741-4520. PMID 17988252. S2CID 32024323.
  12. ^ Stambolliu, Emelina; Ioakeim-Ioannidou, Myrsini; Kontokostas, Kimonas; Dakoutrou, Maria; Kousoulis, Antonis A. (2017-09-01). "The Most Common Comorbidities in Dandy-Walker Syndrome Patients: A Systematic Review of Case Reports" (PDF). Journal of Child Neurology. 32 (10): 886–902. doi:10.1177/0883073817712589. ISSN 0883-0738. PMID 28635420. S2CID 20046766.
  13. ^ a b c d Chen, MD, Harold. "Introduction to Trisomy 18". EMedicine. from the original on 2008-08-04. Retrieved 2008-07-24.
  14. ^ For a description of human karyotype see Mittleman, A., ed. (1995). . Archived from the original on 2006-07-07. Retrieved 2006-06-04.
  15. ^ "Edwards' syndrome (trisomy 18)". nhs.uk. 2017-10-18. Retrieved 2021-07-05.
  16. ^ . Archived from the original on 2018-08-17. Retrieved 2018-08-17.
  17. ^ "Trisomy 18: MedlinePlus Medical Encyclopedia". Nlm.nih.gov. 2011-12-14. from the original on 2012-01-21. Retrieved 2012-01-04.
  18. ^ Rodeck, Charles H.; Whittle, Martin J. (1999). Fetal Medicine: Basic Science and Clinical Practice. Elsevier Health Sciences. ISBN 0-443-05357-X.[permanent dead link]
  19. ^ Zoler, Mitchel L. (March 1, 2003). "Trisomy 13 survival can exceed 1 year". OB/GYN News. Archived from the original on 2012-07-18. Retrieved 2008-07-24.
  20. ^ . Find Articles. 2003-03-01. Archived from the original on 2012-02-21. Retrieved 2012-01-04.
  21. ^ a b Nelson, Katherine E.; Rosella, Laura C.; Mahant, Sanjay; Guttmann, Astrid (2016). "Survival and Surgical Interventions for Children With Trisomy 13 and 18". JAMA. 316 (4): 420–8. doi:10.1001/jama.2016.9819. PMID 27458947. from the original on 17 November 2016. Retrieved 3 December 2016.
  22. ^ "Prevalence and Incidence of Edwards Syndrome". Diseases Center-Edwards Syndrome. Adviware Pty Ltd. 2008-02-04. from the original on 2004-06-25. Retrieved 2008-02-17. mean maternal age for this disorder is 32½
  23. ^ Edwards, J.H.; Harnden, D.G.; Cameron, A.H.; Crosse, V. Mary; Wolff, O.H. (April 9, 1960). "A new trisomic syndrome". The Lancet. 275 (7128): 787–790. doi:10.1016/S0140-6736(60)90675-9. PMID 13819419.
  24. ^ Smith, David W.; Patau, Klaus; Therman, Eeva; Inhorn, Stanley L. (September 1, 1960). "A new autosomal trisomy syndrome: multiple congenital anomalies caused by an extra chromosome". The Journal of Pediatrics. 57 (3): 338–345. doi:10.1016/S0022-3476(60)80241-7. PMID 13831938.
  25. ^ Patau, Klaus; Therman, Eeva; Smith, David W.; DeMars, Robert I. (January 19, 1961). "Trisomy for chromosome no. 18 in man". Chromosoma. Berlin. 12 (1): 280–5. doi:10.1007/BF00328924. PMID 13733243. S2CID 2105207.

External links Edit

  • Trisomy 18 at Curlie
  • Perinatal Hospice Care - Preparing for birth and death" 2007-11-02 at the Wayback Machine
  • Humpath #5389

August 28, 2023
trisomy, also, known, edwards, syndrome, genetic, disorder, caused, presence, third, copy, part, chromosome, many, parts, body, affected, babies, often, born, small, have, heart, defects, other, features, include, small, head, small, clenched, fists, with, ove. Trisomy 18 also known as Edwards syndrome is a genetic disorder caused by the presence of a third copy of all or part of chromosome 18 3 Many parts of the body are affected 3 Babies are often born small and have heart defects 3 Other features include a small head small jaw clenched fists with overlapping fingers and severe intellectual disability 3 Trisomy 18Other namesTrisomy 18 T18 1 chromosome 18 duplication 2 trisomy E syndrome 3 Infant with trisomy 18SpecialtyMedical genetics pediatricsSymptomsSmall head small jaw clenched fists with overlapping fingers profound intellectual disability 3 ComplicationsHeart defects 3 Usual onsetPresent at birth 3 CausesThird copy of chromosome 18 usually new mutation 3 Risk factorsOlder mother 3 Diagnostic methodUltrasound amniocentesis 2 TreatmentSupportive care 2 Prognosis5 10 survive past a year old 3 Frequency1 per 5 000 births 3 Most cases of trisomy 18 occur due to problems during the formation of the reproductive cells or during early development 3 The chance of this condition occurring increases with the mother s age 3 Rarely cases may be inherited 3 Occasionally not all cells have the extra chromosome known as mosaic trisomy and symptoms in these cases may be less severe 3 An ultrasound during pregnancy can increase suspicion for the condition which can be confirmed by amniocentesis 2 Treatment is supportive 2 After having one child with the condition the risk of having a second is typically around one percent 2 It is the second most common condition due to a third chromosome at birth after Down syndrome 4 Trisomy 18 occurs in around 1 in 5 000 live births 3 Many of those affected die before birth 3 Some studies suggest that more babies that survive to birth are female 2 Survival beyond a year of life is around 5 10 3 It is named after English geneticist John Hilton Edwards who first described the syndrome in 1960 5 Contents 1 Signs and symptoms 2 Genetics 3 Diagnosis 4 Prognosis 5 Epidemiology 6 History 7 See also 8 References 9 External linksSigns and symptoms Edit Clenched hand and overlapping fingers index finger overlaps third finger and fifth finger overlaps fourth finger characteristically seen in trisomy 18 This is caused by congenital joint contracture 6 Children born with Edwards syndrome may have some or all of these characteristics kidney malformations structural heart defects at birth i e ventricular septal defect atrial septal defect patent ductus arteriosus intestines protruding outside the body omphalocele esophageal atresia intellectual disability developmental delays growth deficiency feeding difficulties breathing difficulties and arthrogryposis a muscle disorder that causes multiple joint contractures at birth 7 8 Some physical malformations associated with Edwards syndrome include small head microcephaly accompanied by a prominent back portion of the head occiput low set malformed ears abnormally small jaw micrognathia cleft lip cleft palate upturned nose narrow eyelid openings blepharophimosis widely spaced eyes ocular hypertelorism drooping of the upper eyelids ptosis a short breast bone clenched hands choroid plexus cysts underdeveloped thumbs and or nails absent radius webbing of the second and third toes clubfoot or rocker bottom feet and in males undescended testicles 7 8 In utero the most common characteristic is cardiac anomalies followed by central nervous system anomalies such as head shape abnormalities The most common intracranial anomaly is the presence of choroid plexus cysts which are pockets of fluid on the brain These are not problematic in themselves but their presence may be a marker for trisomy 18 9 10 Sometimes excess amniotic fluid or polyhydramnios is exhibited 7 Although uncommon in the syndrome trisomy 18 causes a large portion of prenatally diagnosed cases of Dandy Walker malformation 11 12 Genetics Edit Karyotype of a person with trisomy 18 Three copies of the Chromosome 18 are detected Trisomy 18 is a chromosomal abnormality characterized by the presence of an extra copy of genetic material on the 18th chromosome either in whole trisomy 18 or in part such as due to translocations The additional chromosome usually occurs before conception The effects of the extra copy vary greatly depending on the extent of the extra copy genetic history and chance Trisomy 18 occurs in all human populations but is more prevalent in female offspring 13 A typical egg or sperm cell contains individual chromosomes each of which contributes to the 23 pairs of chromosomes needed to form a normal cell with a typical human karyotype of 46 chromosomes Numerical errors can arise at either of the two meiotic divisions and cause the failure of a chromosome to segregate into the daughter cells nondisjunction This results in an extra chromosome making the haploid number 24 rather than 23 Fertilization of eggs or insemination by sperm that contain an extra chromosome results in trisomy or three copies of a chromosome rather than two 14 Trisomy 18 47 XX 18 is caused by a meiotic nondisjunction event With nondisjunction a gamete i e a sperm or egg cell is produced with an extra copy of chromosome 18 the gamete thus has 24 chromosomes When combined with a normal gamete from the other parent the embryo has 47 chromosomes with three copies of chromosome 18 citation needed A small percentage of cases occur when only some of the body s cells have an extra copy of chromosome 18 resulting in a mixed population of cells with a differing number of chromosomes Such cases are sometimes called mosaic trisomy 18 Very rarely a piece of chromosome 18 becomes attached to another chromosome translocated before or after conception Affected individuals have two copies of chromosome 18 plus extra material from chromosome 18 attached to another chromosome With a translocation a person has a partial trisomy for chromosome 18 and the abnormalities are often less severe than for the typical trisomy 18 15 Diagnosis EditUltrasound can increase suspicion for the condition which can be confirmed by CVS or amniocentesis 2 Levels of PAPP A AFP uE3 free b hCG all of which are generally decreased during pregnancy 16 Prognosis EditAbout 95 of pregnancies that are affected do not result in a live birth 13 Major causes of death include apnea and heart abnormalities It is impossible to predict an exact prognosis during pregnancy or the neonatal period 13 Half of the live infants do not survive beyond the first week of life 17 The median lifespan is five to 15 days 18 19 About 8 12 of infants survive longer than 1 year 20 21 better source needed One percent of children live to age 10 13 However these estimates may be pessimistic a retrospective Canadian study of 254 children with trisomy 18 demonstrated ten year survival of 9 8 and another found that 68 6 of children with surgical intervention survived infancy 21 Epidemiology EditTrisomy 18 occurs in about 1 in 5 000 live births but more pregnancies are affected by the syndrome as the majority of those diagnosed with the condition prenatally will not survive to birth 3 Although women in their 20s and early 30s may conceive babies with trisomy 18 the risk increases with age The average maternal age for conceiving a child with this disorder is 32 5 22 History EditTrisomy 18 was first identified by John Hilton Edwards in 1960 although he originally believed it to be caused by a trisomy of chromosome 17 23 Klaus Patau and Eeva Therman reported another two cases shortly thereafter 24 They identified the extra chromosome as being part of what Patau s lab called group E containing chromosomes 16 17 and 18 but were unable to determine which chromosome was responsible at the time Analyzing 5 more cases they were able to determine that the extra chromosome was in fact chromosome 18 25 See also Edit18q deletion syndromeReferences Edit Edwards syndrome T18 Information for parents a b c d e f g h Trisomy 18 Orphanet May 2008 Archived from the original on 3 October 2016 Retrieved 1 October 2016 a b c d e f g h i j k l m n o p q r s t trisomy 18 GHR March 2012 Archived from the original on 2 October 2016 Retrieved 1 October 2016 Jorde Lynn B Carey John C Bamshad Michael J 2009 Medical Genetics 4 ed Elsevier Health Sciences p 109 ISBN 978 0323075763 Archived from the original on 2016 10 02 Edwards syndrome John Hilton Edwards WhoNamedIt com Archived from the original on 2008 07 09 Retrieved 2008 07 24 Cereda Anna Carey John C 2012 10 23 The trisomy 18 syndrome Orphanet Journal of Rare Diseases 7 81 doi 10 1186 1750 1172 7 81 ISSN 1750 1172 PMC 3520824 PMID 23088440 a b c What is Trisomy 18 Trisomy 18 Foundation Archived from the original on 2009 03 23 Retrieved 2008 07 24 a b Trisomy 18 Medline Archived from the original on 2008 10 01 Retrieved 2008 07 24 Hurt K Sottner O Zahumensky J et al 2007 Choroid plexus cysts and risk of trisomy 18 Modifications regarding maternal age and markers Ceska Gynekol in Czech 72 1 49 52 PMID 17357350 Papp C Ban Z Szigeti Z Csaba A Beke A Papp Z 2007 Role of second trimester sonography in detecting trisomy 18 a review of 70 cases J Clin Ultrasound 35 2 68 72 doi 10 1002 jcu 20290 PMID 17206726 S2CID 23836946 Imataka George Yamanouchi Hideo Arisaka Osamu 2007 Dandy Walker syndrome and chromosomal abnormalities Congenital Anomalies 47 4 113 118 doi 10 1111 j 1741 4520 2007 00158 x ISSN 1741 4520 PMID 17988252 S2CID 32024323 Stambolliu Emelina Ioakeim Ioannidou Myrsini Kontokostas Kimonas Dakoutrou Maria Kousoulis Antonis A 2017 09 01 The Most Common Comorbidities in Dandy Walker Syndrome Patients A Systematic Review of Case Reports PDF Journal of Child Neurology 32 10 886 902 doi 10 1177 0883073817712589 ISSN 0883 0738 PMID 28635420 S2CID 20046766 a b c d Chen MD Harold Introduction to Trisomy 18 EMedicine Archived from the original on 2008 08 04 Retrieved 2008 07 24 For a description of human karyotype see Mittleman A ed 1995 An International System for Human Cytogenetic Nomenclature Archived from the original on 2006 07 07 Retrieved 2006 06 04 Edwards syndrome trisomy 18 nhs uk 2017 10 18 Retrieved 2021 07 05 Prenatal Diagnose Archived from the original on 2018 08 17 Retrieved 2018 08 17 Trisomy 18 MedlinePlus Medical Encyclopedia Nlm nih gov 2011 12 14 Archived from the original on 2012 01 21 Retrieved 2012 01 04 Rodeck Charles H Whittle Martin J 1999 Fetal Medicine Basic Science and Clinical Practice Elsevier Health Sciences ISBN 0 443 05357 X permanent dead link Zoler Mitchel L March 1 2003 Trisomy 13 survival can exceed 1 year OB GYN News Archived from the original on 2012 07 18 Retrieved 2008 07 24 Trisomy 13 survival can exceed 1 year OB GYN News Find Articles 2003 03 01 Archived from the original on 2012 02 21 Retrieved 2012 01 04 a b Nelson Katherine E Rosella Laura C Mahant Sanjay Guttmann Astrid 2016 Survival and Surgical Interventions for Children With Trisomy 13 and 18 JAMA 316 4 420 8 doi 10 1001 jama 2016 9819 PMID 27458947 Archived from the original on 17 November 2016 Retrieved 3 December 2016 Prevalence and Incidence of Edwards Syndrome Diseases Center Edwards Syndrome Adviware Pty Ltd 2008 02 04 Archived from the original on 2004 06 25 Retrieved 2008 02 17 mean maternal age for this disorder is 32 Edwards J H Harnden D G Cameron A H Crosse V Mary Wolff O H April 9 1960 A new trisomic syndrome The Lancet 275 7128 787 790 doi 10 1016 S0140 6736 60 90675 9 PMID 13819419 Smith David W Patau Klaus Therman Eeva Inhorn Stanley L September 1 1960 A new autosomal trisomy syndrome multiple congenital anomalies caused by an extra chromosome The Journal of Pediatrics 57 3 338 345 doi 10 1016 S0022 3476 60 80241 7 PMID 13831938 Patau Klaus Therman Eeva Smith David W DeMars Robert I January 19 1961 Trisomy for chromosome no 18 in man Chromosoma Berlin 12 1 280 5 doi 10 1007 BF00328924 PMID 13733243 S2CID 2105207 External links EditTrisomy 18 at Curlie Perinatal Hospice Care Preparing for birth and death Archived 2007 11 02 at the Wayback Machine Humpath 5389 Retrieved from https en wikipedia org w index php title Trisomy 18 amp oldid 1170694551, wikipedia, wiki, book, books, library,

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