Edwards Syndrome

from Wikipedia, the free encyclopedia
Classification according to ICD-10
Q91.0 Trisomy 18, meiotic non-disjunction
Q91.1 Trisomy 18, mosaic (mitotic non-disjunction)
Q91.2 Trisomy 18, translocation
Q91.3 Edwards syndrome, unspecified
ICD-10 online (WHO version 2019)

The Edwards syndrome of Man will also Trisomy 18 , Trisomy E or E1 trisomy named because it on aneuploidy of the 18th chromosome is based, the triple ( trisom ) is present. This chromosome aberration allocates excess genetic material to a cell nucleus. As a genome mutation , it causes a variety of physical characteristics and leads to disabilities that cannot be cured. The syndrome is associated with higher than average child mortality rates during pregnancy. But even after that, infant mortality is high: half of newborns die within about 6 days. Only 15% of girls reach the age of 5. Trisomy 18 is the second most common aneuploidy after trisomy 21 . In rare cases, trisomy 18 and trisomy 21 occur together.

The syndrome is not to be confused with orofacio-digital syndrome of the Edward type .

History / discovery

The syndrome was first described in 1960 by the British human geneticist John Hilton Edwards as a result of a tripling ( trisomy ) of genetic material of the 18th chromosome and named after him.

The numerous anatomical anomalies of the syndrome were first compiled by Jean de Grouchy.

Frequency of occurrence

The risk of having a child with trisomy 18 is highly dependent on the age of the mother. For an eighteen-year-old woman, the risk of having a child with trisomy 18 in the womb in the 12th week of pregnancy is about 1: 2500. This risk increases to about 1: 180 for a woman of forty. Since around 80 percent of children with trisomy 18 die in the womb between the 12th week of pregnancy and birth, the probability of having a child is accordingly about a factor of 5 to 6 lower than indicated for the 12th week of pregnancy. This makes Edwards syndrome the second most common disease caused by a trisomy among live born children, after Down's syndrome ( trisomy 21 ).

Girls are affected significantly more often than boys: out of 100 children with Edwards syndrome, an average of 75 are female and 25 are male ( gynecotropy / ratio f: m = 3: 1).

Emergence

In people with trisomy 18, chromosome 18 or part of it is present three times (= trisome ) instead of usually two times (= disome ) in all or some of the body cells. The following types are distinguished:

Free trisomy 18

In most people with Edwards syndrome (approx. 95%) all cells in the body have triplicate chromosome 18. This form of the syndrome occurs when one of the germ cells contains an extra chromosome 18. The error occurs when the chromosome pair 18 is not separated as usual (like the other chromosome pairs) during the formation of the egg cells or sperm cells. Such a non-disjunction occurs accidentally in meiosis . The incidence of free trisomy 18 increases with the age of the mother, although every woman of childbearing potential at any age can expect a child with trisomy 18. The karyotype of free trisomy 18 is 47, XX, + 18 for a girl and 47, XY, + 18 for a boy.

Mosaic trisomy 18

In genetics, a mosaic is understood to be the presence of several karyotypes in the same organism. In mosaic trisomy 18, which affects about 3% of people with Edwards syndrome, a trisome and a disome cell line coexist. Some of the body's cells have normal nuclei with 2n = 46, the other cells have diseased nuclei with 47 chromosomes. The karyotype of the mosaic is therefore formulated as 46, XX / 47, XX, + 18 or 46, XY / 47, XY, + 18. After fertilization, the first divisions proceed normally, so that regular mitoses result in disome cell nuclei. If, however, the separation of the sister chromatids from chromosome 18 is not carried out, a cell nucleus receives the 18 threefold. In this case, non-disjunction occurs in mitosis and is the origin of the trisome cell line. Such a pathological chromosome distribution causes monosomy 18 in the other (sibling) cell nucleus at the same time. However, the mosaic formula ignores this event because complete monosomy of an autosome is fatal for the affected cell.

The later in embryogenesis the chromatids of chromosome 18 are incorrectly distributed, the fewer trisome cells arise. The more disome cells that remain, the weaker the symptoms of the syndrome appear.

Partial trisomy 18

This type occurs in about 2% of people with Edwards syndrome. In partial (partial) trisomy 18, chromosomes 18 are present in duplicate in all body cells as usual, but part of one of the two chromosomes 18 is duplicated. As a result, one of chromosomes 18 is slightly longer than the other, and the affected cell nuclei contain the genetic information of this section three times. People with partial trisomy 18 do not show the features of the syndrome to a high degree. But this expectation is not to be generalized, but always to be considered on a case-by-case basis, because the expression in each case depends on the information content of the triple chromosome segment.

Translocation trisomy

The type in which the trisome chromosome material from chromosome 18 attaches to another chromosome is very rare, and therefore hardly mentioned in the statistics. This change in the location of chromosomes is called translocation in genetics , the form of trisomy 18 is called translocation trisomy 18. The karyotype is, depending on the chromosome with which the connection is made, for example: 46, XX, t (18; 22) or 46, XY, t (18; 22). In the case of a translocation trisomy 18, one parent may in some cases be the "carrier" . A balanced translocation of an 18th chromosome can be demonstrated in such a parent . The karyogram shows 45 instead of 46 individual chromosomes because two chromosomes have joined together. Since no relevant genetic material is lost or added to this peculiarity, the genetic information is in equilibrium (= balanced ) and the person does not experience trisomy 18. However, the probability that the person concerned will father a child with a translocation trisomy 18 is increased. If both chromosomes 18 have combined with each other in a balanced translocation in one of the parents, a child conceived by the person concerned always has a translocation trisomy 18/18.

Symptoms

Signs of trisomy 18 are always combined in a child, although not all affected children have all the characteristics or not all characteristics are equally pronounced.

Common features before birth (prenatal)

In the course of the steadily developing possibilities of prenatal examinations ( prenatal diagnosis ), some peculiarities have been documented over time, which can often be detected in babies with Edwards syndrome before birth. Only about 15 out of 100 children with trisomy 18 cannot find any prenatal signs.

The almost certain diagnosis of trisomy 18 is only possible through a chromosome examination. Prenatally, invasive examination procedures ( e.g. chorionic villus sampling , amniocentesis ) or the chromosome analysis that follow these methods are no longer necessary . Instead, tests are now available that can analyze gene fragments from the fetus in the mother's blood.

The features that can indicate the presence of a trisomy 18 in the unborn child, especially in combination with one another , and which can sometimes be recognized by ultrasound or blood tests , include, for example:

heart

Skull, brain, face

extremities

  • Flexion contracture of the fingers: often the index fingers are above the middle and ring fingers and / or the little fingers are above the ring fingers so that the fist cannot be opened ( clenched fist )
  • Malformation or absence of the thumb
  • Absence of the radial bone on the forearm ( radial aplasia )
  • Polydactyly (extra fingers and / or toes)
  • comparatively short thigh ( femur ) and humerus ( humerus )
  • Ink eraser feet ( rocker bottom feet , innate flat feet with outwardly arched soles or with inward arched backs of the feet or club feet )
  • a sandal gap / sandal furrow (increased distance between the first and second toe )
  • comparatively short big toes, protruding heel bone ( calcaneus )

Abdomen

Others

  • a comparatively small baby (early growth deficit, often before the 18th week of pregnancy, later mostly low birth weight) in 50% of children
  • a comparatively large amount of amniotic fluid ( polyhydramnios ) in about 25% of children
  • in the triple test frequently decreased values ​​for AFP, HCG and estriol; AFP value often below 60% of the usual median value
  • Placental insufficiency (poor performance of the mother cake)
  • sometimes significantly reduced child movements are noticeable during pregnancy

Common postpartum features (postnatal)

In many children with trisomy 18, other peculiarities can be determined after birth. Not all children have all characteristics or not all characteristics can be identified to the same extent. The most common features include:

diagnosis

Edwards syndrome can be suspected prenatally based on certain signs (see above) and after birth (postnatally) based on external features (suspected diagnosis). During pregnancy it is possible to diagnose trisomy 18 in the unborn child with a high degree of certainty by means of a chromosome analysis. The material required for this analysis must contain cells from the unborn child and is obtained through an invasive examination ( e.g. chorionic villus sampling or amniocentesis ). A prenatal chromosome analysis is open to all women in Germany and must be offered to women aged 35 and over.

A chromosome examination must follow for an almost 100 percent reliable diagnosis after the birth. A chromosome analysis from lymphocytes of the blood can not only confirm the diagnosis, but also determine the type of trisomy 18 (free trisomy 18, translocation trisomy 18, mosaic trisomy 18).

The differential diagnoses are Freeman-Sheldon syndrome , Pena-Shokeir syndrome ( pseudo-trisomy 18 ), Smith-Lemli-Opitz syndrome , Réthore syndrome , triploidy , cerebro-costo-mandibular syndrome and other syndromes with prenatal growth retardation in question.

development

Free trisomy 18 in particular usually causes severe disabilities. Gross motor skills (sitting, crawling, standing, walking) are developed much later than regular children.

The use of expressive spoken language (speech expression) is rarely possible for children with trisomy 18; many children learn supportive signs faster and better (for example using methods such as the GuK principle). Your receptive language (language understanding) can, however, be rated as significantly better.

A survey of twelve parents of a child with Edwards syndrome revealed the following: " The parents of the children who survived longer than a year reported in retrospect that most children learned to follow things in the course of the first year and made their first simple sounds, Rolled on their side, smiled responsively, reached for things and recognized familiar adults. In the next two years, supported or free sitting succeeded in many cases. They noted where an attractive object was, made the first attempts to imitate it, participated At the age of 4 to 6, some children managed to crawl, independent play in a simple form, were able to carry out simple prompts, help with body care, stand independently, perceive relationships and use first gestures. The oldest Children could run free and understand simple commands Running and linguistic communication has only been reported in individual cases "(Sarimski, 2003, page 456 in relation to Ray et al. 1986 and Woldorf & Johnson, 1994).

As food intake is often difficult, many children are fed at least temporarily through a gastric tube. In the studies cited above, it was 66%. 8% could be breastfed and 33.2% were bottle-fed (cf. ibid.).

forecast

Trisomy 18 cannot be cured causally. 95% of cases die before birth . Of the children who survive their birth, a further 87% –95% die in the course of the first year of life. Their lifespan depends to a large extent on which peculiarities (especially in the physical-organic area) are present in them and whether they are adequately medically and socially treated after the birth . Depending on the proportion of disomic cells, the symptoms in children with the mosaic type of trisomy 18 are usually less severe and their life expectancy is often more favorable. The same applies to children with a partial trisomy 18. On average, girls have a higher life expectancy than boys. In particular, " if a child does not have any serious organ malformations or does not depend entirely on any oxygen supply in the first few weeks , there is a good prospect of a longer lifetime ": Around 40 out of 100 children born reach the first and 15 out of 100 girls the fifth with treatment Age. The most common causes of death in children / adolescents with trisomy 18 are currently cardiac arrest , circulatory failure and respiratory failure . Only a few patients with trisomy 18 reach adolescence and young adulthood.

Repetition probability

Trisomy 18 cannot be brought about by anything. A general prophylaxis (prevention) is not possible. The option of (late) abortion for medical reasons can at most prevent the live birth of the child after the confirmed prenatal diagnosis.

For a woman who was already pregnant with a child with free trisomy 18, the likelihood of having another child with Edwards syndrome is slightly (1%) higher than the likelihood for her corresponding age group. The slight increase results from the possibility of a mosaic in the parental germ cells, which cannot be ruled out .

The same applies to a translocation trisomy 18 if the parent's chromosome findings are normal. However, there is no age dependency here. If a balanced translocation of an 18th chromosome is detected in one of the parents , the probability for children with the translocation type of the syndrome is theoretically 25%. However, empirical values ​​are far below that, since with chromosomal imbalance the fetus often dies prematurely and often unnoticed by the pregnant woman. However, the probability of trisomy 18 in a child is 100% if the two chromosomes 18 of a pair are connected to one another in the balanced translocation of one parent ( translocation 18/18 ). This is extremely rare.

See also

Individual evidence

  1. ^ H Goldstein, KG Nielsen: Rates and survival of individuals with trisomy 13 and 18 data from a 10-year period in Denmark. In: Clinical Genetics Volume 34, 1988: 366-372, doi: 10.1111 / j.1399-0004.1988.tb02894.x .
  2. ↑ W Roberts, A Zurada, A Zurada-Zielinska, J Gielecki, M Loukas: Anatomy of trisomy 18 in: Clin Anat 29 (5), 2016: 628-632, doi: 10.1002 / ca.22725 .
  3. ↑ PK Grosse, G Schwanitz: Double autosomal trisomy: Case report (48, XX, +18, +21) and review of the literature. In: J Mental Deficiency Research 21, 1978: 299-308. doi: 10.1111 / j.1365-2788.1977 .tb01593.x.
  4. ↑ JH Edwards, DG Harnden, AH Cameron, VM Crosse, OH Wolff: A new trisomic syndrome. In: The Lancet , Vol. 1, 1960, pp. 787-790, PMID 13819419 .
  5. ^ Jean de Grouchy: Clinical cytogenetics: autosomal disorders. In: H Busch (ed): The cell nucleus. Academic, New York 1974, pp. 371-414.
  6. ↑ W Roberts, A Zurada, A Zurada-Zielinska, J Gielecki, M Loukas: Anatomy of trisomy 18 in: Clin Anat 29 (5), 2016: 628-632, doi: 10.1002 / ca.22725 .
  7. ↑ K. Spencer in: Prenat. Diagn. Volume 22, 2002, pp. 877-879.
  8. ↑ JH Donovan, G Krigbaum, DA Bruns: Medical interventions and survival by gender of children with trisomy 18. Am J Med Genet C Semin Med Genet 172 (3), 2016: 272–278, doi: 10.1002 / ajmg.c.31522 .
  9. ^ Adrian T Sumner: Chromosomes: Organization and function. Blackwell Publishing, Berlin 2003. There p. 206. ISBN 0-632-05407-7 .
  10. ↑ Chih-Ping Chen, Fang-Yu Hung, Schu-Rern Chern et al .: Prenatal diagnosis of low-level mosaicism for trisomy 18 associated with a favorable fetal outcome. In: Taiwanese J Obstetrics & Gynecology 55 (6), 2016: 902-903. [1] PDF
  11. ↑ http://www.zeit.de/2015/04/praenataldiagnostik-down-syndrom-krankenkasse , accessed on February 9, 2015
  12. ↑ a b Harold Chen, MD: Introduction to Trisomy 18 . EMedicine. August 8, 2007. Archived from the original on August 4, 2008. Retrieved October 12, 2019.
  13. ↑ Katherine E. Nelson, Laura C. Rosella, Sanjay Mahant, Astrid Guttmann: Survival and Surgical Interventions for Children With Trisomy 13 and 18 Archived from the original on November 17, 2016. In: JAMA . 316, No. 4, 2016, p. 420. doi : 10.1001 / jama.2016.9819 . Retrieved October 12, 2019.
  14. ↑ Sarimski, 2003, page 456

literature

  • Müller / Bruehwiler: HELLP syndrome and trisomy 18 in a multipara in: Zeitschrift für Obstetrilfe und Neonatologie; 200; 3; 119-121; 1996
  • Sommer / Dunitz: Psychosomatic care and support for trisomy 18 in: Pediatric nurse; 13; 6; 197-198; 1994
  • Klaus Sarimski: Developmental Psychology of Genetic Syndromes (3rd edition, 2003)
  • D. Scott Showalter, John C. Carey: A guide for professionals
  • Ann M. Barnes, John Carey: Common problems of babies with trisomy 18 or 13. , 1998
  • Barnes, Carey: Care of the infant and child with trisomy 18 or 13: medical problems, reported treatments and milestones , 1996