Trisomy 18

Last updated
Trisomy 18
Other namesTrisomy 18 (T18 [1] ), chromosome 18 duplication, [2] trisomy E syndrome [3]
Trisomy 17-18 2.jpg
Infant with trisomy 18
Specialty Medical genetics, pediatrics
Symptoms Small head, small jaw, clenched fists with overlapping fingers, profound intellectual disability [3]
Complications Heart defects [3]
Usual onsetPresent at birth [3]
CausesThird copy of chromosome 18 (usually new mutation) [3]
Risk factors Older mother [3]
Diagnostic method Ultrasound, amniocentesis [2]
Treatment Supportive care [2]
Prognosis 5–10% survive past a year old [3]
Frequency1 per 5,000 births [3]

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.

Contents

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 for a third chromosome 21. [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 the English geneticist John Hilton Edwards, who first described the syndrome in 1960. [5]

Signs and symptoms

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. Overlapping fingers.JPG
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.

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

Karyotype of a person with trisomy 18. Three copies of the Chromosome 18 are detected. Trisomia 18.jpg
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. In nondisjunction, a pair of chromosomes fails to separate during cell division; thus, a gamete (i.e., a sperm or egg cell) is produced with an extra copy of chromosome (for a total of 24 chromosomes). When combined with a normal gamete from the other parent, the resulting embryo has 47 chromosomes, with three copies of the problematic chromosome (in this case, chromosome 18). (Although an embryo could inherit a trisomy from both parents, it is, as a rule, extremely rare, and worse in terms of clinical perspective and prognosis.)

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

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

Levels of PAPP-A, AFP, uE3, all of which are generally decreased during pregnancy and free beta HCG which is elevated. [16]

Prognosis

About 95% of pregnancies that are affected do not result in a live birth. [13] Major causes of death include hypoxia 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, 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] Though rare, some persons with Trisomy 18 do survive into their twenties and thirties. [22]

Epidemiology

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. [23]

History

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. [24] Klaus Patau and Eeva Therman reported another two cases shortly thereafter. [25] 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. [26]

See also

Related Research Articles

<span class="mw-page-title-main">Autosome</span> Any chromosome other than a sex chromosome

An autosome is any chromosome that is not a sex chromosome. The members of an autosome pair in a diploid cell have the same morphology, unlike those in allosomal pairs, which may have different structures. The DNA in autosomes is collectively known as atDNA or auDNA.

<span class="mw-page-title-main">Trisomy</span> Abnormal presence of three copies of a particular chromosome

A trisomy is a type of polysomy in which there are three instances of a particular chromosome, instead of the normal two. A trisomy is a type of aneuploidy.

<span class="mw-page-title-main">Aneuploidy</span> Presence of an abnormal number of chromosomes in a cell

Aneuploidy is the presence of an abnormal number of chromosomes in a cell, for example a human cell having 45 or 47 chromosomes instead of the usual 46. It does not include a difference of one or more complete sets of chromosomes. A cell with any number of complete chromosome sets is called a euploid cell.

<span class="mw-page-title-main">Patau syndrome</span> Chromosomal disorder in which there are three copies of chromosome 13

Patau syndrome is a syndrome caused by a chromosomal abnormality, in which some or all of the cells of the body contain extra genetic material from chromosome 13. The extra genetic material disrupts normal development, causing multiple and complex organ defects.

<span class="mw-page-title-main">Nondisjunction</span> Failure to separate properly during cell division

Nondisjunction is the failure of homologous chromosomes or sister chromatids to separate properly during cell division (mitosis/meiosis). There are three forms of nondisjunction: failure of a pair of homologous chromosomes to separate in meiosis I, failure of sister chromatids to separate during meiosis II, and failure of sister chromatids to separate during mitosis. Nondisjunction results in daughter cells with abnormal chromosome numbers (aneuploidy).

<span class="mw-page-title-main">Prenatal testing</span> Testing for diseases or conditions in a fetus

Prenatal testing is a tool that can be used to detect some birth defects at various stages prior to birth. Prenatal testing consists of prenatal screening and prenatal diagnosis, which are aspects of prenatal care that focus on detecting problems with the pregnancy as early as possible. These may be anatomic and physiologic problems with the health of the zygote, embryo, or fetus, either before gestation even starts or as early in gestation as practicable. Screening can detect problems such as neural tube defects, chromosome abnormalities, and gene mutations that would lead to genetic disorders and birth defects, such as spina bifida, cleft palate, Down syndrome, trisomy 18, Tay–Sachs disease, sickle cell anemia, thalassemia, cystic fibrosis, muscular dystrophy, and fragile X syndrome. Some tests are designed to discover problems which primarily affect the health of the mother, such as PAPP-A to detect pre-eclampsia or glucose tolerance tests to diagnose gestational diabetes. Screening can also detect anatomical defects such as hydrocephalus, anencephaly, heart defects, and amniotic band syndrome.

<span class="mw-page-title-main">Robertsonian translocation</span> Human chromosomal abnormality

Robertsonian translocation (ROB) is a chromosomal abnormality where the entire long arms of two different chromosomes become fused to each other. It is the most common form of chromosomal translocation in humans, affecting 1 out of every 1,000 babies born. It does not usually cause medical problems, though some people may produce gametes with an incorrect number of chromosomes, resulting in a risk of miscarriage. In rare cases this translocation results in Down syndrome and Patau syndrome. Robertsonian translocations result in a reduction in the number of chromosomes. A Robertsonian evolutionary fusion, which may have occurred in the common ancestor of humans and other great apes, is the reason humans have 46 chromosomes while all other primates have 48. Detailed DNA studies of chimpanzee, orangutan, gorilla and bonobo apes has determined that where human chromosome 2 is present in our DNA in all four great apes this is split into two separate chromosomes typically numbered 2a and 2b. Similarly, the fact that horses have 64 chromosomes and donkeys 62, and that they can still have common, albeit usually infertile, offspring, may be due to a Robertsonian evolutionary fusion at some point in the descent of today's donkeys from their common ancestor.

<span class="mw-page-title-main">Coloboma</span> Hole in one of the structures of the eye

A coloboma is a hole in one of the structures of the eye, such as the iris, retina, choroid, or optic disc. The hole is present from birth and can be caused when a gap called the choroid fissure, which is present during early stages of prenatal development, fails to close up completely before a child is born. Ocular coloboma is relatively uncommon, affecting less than one in every 10,000 births.

Trisomy 8 causes Warkany syndrome 2, a human chromosomal disorder caused by having three copies (trisomy) of chromosome 8. It can appear with or without mosaicism.

<span class="mw-page-title-main">Polysomy</span> Abnormal multiples of one or more chromosomes

Polysomy is a condition found in many species, including fungi, plants, insects, and mammals, in which an organism has at least one more chromosome than normal, i.e., there may be three or more copies of the chromosome rather than the expected two copies. Most eukaryotic species are diploid, meaning they have two sets of chromosomes, whereas prokaryotes are haploid, containing a single chromosome in each cell. Aneuploids possess chromosome numbers that are not exact multiples of the haploid number and polysomy is a type of aneuploidy. A karyotype is the set of chromosomes in an organism and the suffix -somy is used to name aneuploid karyotypes. This is not to be confused with the suffix -ploidy, referring to the number of complete sets of chromosomes.

The Pallister–Killian syndrome (PKS), also termed tetrasomy 12p mosaicism or the Pallister mosaic aneuploidy syndrome, is an extremely rare and severe genetic disorder. PKS is due to the presence of an extra and abnormal chromosome termed a small supernumerary marker chromosome (sSMC). sSMCs contain copies of genetic material from parts of virtually any other chromosome and, depending on the genetic material they carry, can cause various genetic disorders and neoplasms. The sSMC in PKS consists of multiple copies of the short arm of chromosome 12. Consequently, the multiple copies of the genetic material in the sSMC plus the two copies of this genetic material in the two normal chromosome 12's are overexpressed and thereby cause the syndrome. Due to a form of genetic mosaicism, however, individuals with PKS differ in the tissue distributions of their sSMC and therefore show different syndrome-related birth defects and disease severities. For example, individuals with the sSMC in their heart tissue are likely to have cardiac structural abnormalities while those without this sSMC localization have a structurally normal heart.

<span class="mw-page-title-main">Genetics of Down syndrome</span>

Down syndrome is a chromosomal abnormality characterized by the presence of an extra copy of genetic material on chromosome 21, either in whole or part. The effects of the extra copy varies greatly from individual to individual, depending on the extent of the extra copy, genetic background, environmental factors, and random chance. Down syndrome can occur in all human populations, and analogous effects have been found in other species, such as chimpanzees and mice. In 2005, researchers have been able to create transgenic mice with most of human chromosome 21.

A chromosomal abnormality, chromosomal anomaly, chromosomal aberration, chromosomal mutation, or chromosomal disorder is a missing, extra, or irregular portion of chromosomal DNA. These can occur in the form of numerical abnormalities, where there is an atypical number of chromosomes, or as structural abnormalities, where one or more individual chromosomes are altered. Chromosome mutation was formerly used in a strict sense to mean a change in a chromosomal segment, involving more than one gene. Chromosome anomalies usually occur when there is an error in cell division following meiosis or mitosis. Chromosome abnormalities may be detected or confirmed by comparing an individual's karyotype, or full set of chromosomes, to a typical karyotype for the species via genetic testing.

Klaus Patau was a German-born American geneticist. He received his PhD from the University of Berlin in 1936, worked from 1938 to 1939 in London, and then returned to Germany, where he worked at the Kaiser Wilhelm Institute for Biology until 1947. He emigrated to the United States in 1948 and obtained American citizenship. In 1960 he first reported the extra chromosome in trisomy 13. The syndrome caused by trisomy 13 is often called Patau syndrome. It is also known as Bartholin-Patau syndrome, since the clinical picture associated with trisomy 13 was described by Thomas Bartholin in 1656. At the time, laboratory techniques were unable to distinguish between chromosomes of similar size, so chromosomes were grouped into seven groups by size, lettered A through G. Chromosomes 13 through 15 were in group D, so Patau originally named his eponymous syndrome "trisomy D".

<span class="mw-page-title-main">Trisomy 22</span> Medical condition

Trisomy 22 is a chromosomal disorder in which three copies of chromosome 22 are present rather than two. It is a frequent cause of spontaneous abortion during the first trimester of pregnancy. Progression to the second trimester and live birth are rare. This disorder is found in individuals with an extra copy or a variation of chromosome 22 in some or all cells of their bodies.

<span class="mw-page-title-main">Eeva Therman</span> Finnish geneticist (1916–2004)

Eeva Maria Therman-Patau (1916–2004) was a Finnish-born American geneticist. She worked to characterize the effects and cytogenetics of trisomy 13 and trisomy 18, two rare and usually fatal genetic disorders caused by an extra copy of chromosome 13 and 18, respectively. Her works include Human Chromosomes: Structure, Behavior, Effects, a textbook on cytogenetics which is in its 4th edition. Her research specialties included X-inactivation in mammals and chromosomal abnormalities in cancer.

<span class="mw-page-title-main">Tetrasomy X</span> Chromosomal disorder with 4 X chromosomes

Tetrasomy X, also known as 48,XXXX, is a chromosomal disorder in which a female has four, rather than two, copies of the X chromosome. It is associated with intellectual disability of varying severity, characteristic "coarse" facial features, heart defects, and skeletal anomalies such as increased height, clinodactyly, and radioulnar synostosis. Tetrasomy X is a rare condition, with few medically recognized cases; it is estimated to occur in approximately 1 in 50,000 females.

<span class="mw-page-title-main">Pentasomy X</span> Chromosomal disorder

Pentasomy X, also known as 49,XXXXX, is a chromosomal disorder in which a female has five, rather than two, copies of the X chromosome. Pentasomy X is associated with short stature, intellectual disability, characteristic facial features, heart defects, skeletal anomalies, and pubertal and reproductive abnormalities. The condition is exceptionally rare, with an estimated prevalence between 1 in 85,000 and 1 in 250,000.

<span class="mw-page-title-main">Trisomy X</span> Chromosome disorder in women

Trisomy X, also known as triple X syndrome and characterized by the karyotype 47,XXX, is a chromosome disorder in which a female has an extra copy of the X chromosome. It is relatively common and occurs in 1 in 1,000 females, but is rarely diagnosed; fewer than 10% of those with the condition know they have it.

<span class="mw-page-title-main">XXXYY syndrome</span> Chromosomal disorder

XXXYY syndrome, also known as 49,XXXYY, is a chromosomal disorder in which a male has three copies of the X chromosome and two copies of the Y chromosome. XXXYY syndrome is exceptionally rare, with only eight recorded cases. Little is known about its presentation, but associated characteristics include intellectual disability, anomalies of the external genitalia, and characteristic physical and facial features. It is not caused by characteristics of the parents, but rather occurs via nondisjunction, a random event in gamete development. The karyotype observed in the syndrome is formally known as 49,XXXYY, which represents the 49 chromosomes observed in the disorder as compared to the 46 in normal human development.

References

  1. ↑ "Edwards' syndrome (T18): Information for parents". December 2020.
  2. 1 2 3 4 5 6 7 8 "Trisomy 18". Orphanet. May 2008. Archived from the original on 3 October 2016. Retrieved 1 October 2016.
  3. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 "trisomy 18". GHR. March 2012. Archived 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. Archived from the original on 2016-10-02.
  5. ↑ "Edwards syndrome (John Hilton Edwards)". WhoNamedIt.com. Archived 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. 1 2 3 "What is Trisomy 18?". Trisomy 18 Foundation. Archived from the original on 2009-03-23. Retrieved 2008-07-24.
  8. 1 2 "Trisomy 18". Medline. Archived 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. 1 2 3 4 Chen, MD, Harold. "Introduction to Trisomy 18". EMedicine. Archived from the original on 2008-08-04. Retrieved 2008-07-24.
  14. ↑ 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.
  15. ↑ "Edwards' syndrome (trisomy 18)". nhs.uk. 2017-10-18. Retrieved 2021-07-05.
  16. ↑ "Prenatal Diagnose". Archived from the original on 2018-08-17. Retrieved 2018-08-17.
  17. ↑ "Trisomy 18: MedlinePlus Medical Encyclopedia". Nlm.nih.gov. 2011-12-14. Archived 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. ↑ "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.
  21. 1 2 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.
  22. ↑ Alshami, Abbas; Douedi, Steven; Guida, Melissa; Ajam, Firas; Desai, Dhaval; Zales, Vincent; Calderon, Dawn M (7 December 2020). "Unusual Longevity of Edwards Syndrome: A Case Report". Genes. 11 (12): 1466. doi: 10.3390/genes11121466 . ISSN   2073-4425. PMC   7762407 . PMID   33297534.
  23. ↑ "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 32½
  24. ↑ 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.
  25. ↑ 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.
  26. ↑ Patau, Klaus; Therman, Eeva; Smith, David W.; DeMars, Robert I. (January 19, 1961). "Trisomy for chromosome no. 18 in man". Chromosoma. 12 (1). Berlin: 280–5. doi:10.1007/BF00328924. PMID   13733243. S2CID   2105207.
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