Syndrome of Down - SpeedyLook encyclopedia

The syndrome of Down , also called trisomy 21 , is a chromosomal Maladie congenital caused by the presence of a supernumerary chromosome for the 21 {{E}} even. Its clinical signs are very Nets, one observes a cognitive delay, associated with particular morphological modifications.

The disease was described by the British doctor John Langdon Down in an article of 1866. He is the author of the words mongolien and mongolism , suggested in reference to the attached eyes of the subjects reached by the syndrome (the use of these terms is officially disadvised today).

The chromosomal origin of this disease was discovered by Jerome Lejeune, French doctor, in July 1958. It was the first disease for which was highlighted the relation between the Génotype and the Phénotype. It gave him the name of " trisomy 21" what breaks up into " tri" wanting to say " trois" , " some" wanting to say " chromosome": i.e. three chromosomes 21.

Clinical description

Morphology of the patients

The people reached of this syndrome have in particular small a size, member S courts, a round facies, a nape of the neck punt, palpebral slits (of the Paupière S) oblique and narrow with a fold of the cutaneous angle interns eyelids (épicanthus). The Oreille S are established low, badly hemmed. Another characteristic sign is a Langue thick, associated rather often with a narrow Mâchoire, involving, in the absence of operation, a considerable embarrassment for the patient and bringing it, especially in the child, to frequently leave it the mouth (protrusion of the language). The hands are barred of only one very marked palmar fold, the fingers are short. The musculo-skeletal anomalies are constant and source of complications (Scoliose, Luxation S, articular instability, etc): muscular Hypotonia and Hyperlaxité Ligament surface. Malformation S of body are very frequent and will have to be required as of the diagnosis of certainty posed (by the chromosomic chart, to see low): atrio-ventricular channel, digestive atresy, urinary, ocular, ostéo-articular anomalies.

Psychomotricity

the Backwardness is heterogeneous: goes from light (60) to deep (30)
acquisitions are delayed (Marche around 2 years, Langage)
the development of the aptitudes social and emotional is, in the large majority of the case, normal.

Growth

The final size is generally lower than the average.

Adolescence and puberty, will involve as in the other young people, of the sexual and emotional behaviors which will require to be accompanied, explained by the adults. Groups of word with a professional can enable them to advance in the construction of their identity of teenager and adult. A trisomic woman 21 has a probability of 50% of having a child reached. Ageing is accelerated.

Causes of the syndrome of Down

The presence of a third chromosome 21 is the cause of pathology. The mechanism of the presence of the additional chromosome is important to know for the genetic council. The realization of the Caryotype makes it possible to know the mechanism.

Trisomy 21 free

The chromosomal Formule of the person reached of trisomy 21 is thus 47,21+ . Additional chromosome 21 almost always comes from the mother. The origin of this genetic disease is at the time of the Gamétogénèse, and more precisely with the bad distribution of the chromosomes homologous during the first Métaphase with the Méiose. One of the Gamète S thus formed will comprise two Chromosome S of the even 21e, instead of only one, which, after Fécondation of this gamète by another “normal” will form a cell egg whose even 21e has 3 chromosomes.

Trisomy 21 by translocation

It is about the fusion of two Chromosome S 21 by the mechanism known as of Translocation. It is thus about an apparent chromosome having the genetic contents of two chromosomes. The chromosomal formula of the person reached of this form of trisomy 21 is thus 45, XY DER (21) T (21; 21) or 45, XX DER (21) T (21; 21) . Trisomy 21 by translocation is always inherited the one of the parents. It is necessary in this case to practice a chromosomic chart in the parents if one wants to identify the carrier of the anomaly.

Anténatale evaluation of the risk of trisomy 21

Trisomy 21 is the most frequent cause of Backwardness responsible for 25% of the mental handicaps in the children of school age. It is, among the chromosomal anomalies observed in the course of pregnancy, about that whose incidence is highest: in the neighborhoods of 1/770 births is 1,3/1000 births. Currently, with the use of modern technologies of tracking the proportion was pushed back with 1/2000 births. In France one belongs to 65.000 to 70.000 individuals carrying trisomy 21.

The possibility of making it possible to the parents to know the risk to have a child reached of this disease thus appeared obvious.

The principle of the evaluation thus consists in evaluating the risk of trisomy 21 in order to be able to decide if the risk of the puncture is tolerable. The goal of the evaluation of the risk is, when the risk is raised, to make it possible to the future parents to decide or not to practice a Amniocentèse in order to make the diagnosis. The tolerance level is an arbitrary choice, it is indeed difficult to compare the risk to kill a healthy fetus with that to allow the birth of a trisomic child.

The goal of the examinations of tracking is according to one or several clinical parameters or para-private clinics, to separate the expectant mothers in two pennies populations:

a population whose risk is judged low and for which one will abstain from carrying out any invasive taking away while explaining to him nevertheless why the null risk does not exist and that it must thus not ignore the fact that a tiny risk persists.
a population considered high-risk for which an invasive examination will be proposed with the couple after information concerning the risk related to the method of diagnosis employed.

The evaluation of a risk calls upon statistical methods and following probabilities:

To have relevant signs, i.e. to know the sensitivity, specificity, the positive and negative predictive value and finally the prevalence of the sign.

In practice, the calculation of the risk of trisomy 21

The calculation of the risk is based on the risk a priori which is function of the age gestationnel and the age of the mother. Indeed, the risk of trisomy 21 decreases during the pregnancy because approximately 30% of the fetuses reached of trisomy 21 die in utero .

Before the test, a woman has a risk to have a fetus reached of trisomy 21: it is the pretest risk. After the test, a woman has a risk to have a fetus reached of trisomy 21: it is the post-test risk. The report/ratio of probability or likehood ratio is the multiplying number which makes it possible to pass from the pretest risk to the post-test risk.

If a sign is present in 50% of the fetuses reached from trisomy and 5% at the fetuses unfulfilled, the report/ratio of probability is of 10 i.e. the risk is multiplied by 10. The report/ratio of probability is also true in the other direction. If a sign is present in 20% of the fetuses reached from trisomy and 40% at the fetuses unfulfilled, the report/ratio of probability is of 0,5 i.e. the risk is divided by 2.

It is necessary also to be on which the signs used are not dependant between them i.e. one does not depend on the other. It is necessary that the signs is statistically independent.

The integrated risk carried out by certain obstetricians i.e. the risk given by the measurement of clearness nucale and risks it given by proportionings of the H.C.G and of the alpha-fetoprotein (the blood test suggested in France with all the expectant mothers) is the integration of all the reports/ratios of probability. It requires the use of software which eliminates the maternal risk in one from two calculations.

the risk from which a chromosomic chart is carried out depends on the countries; it is of 1/300 in England and 1/250 in France.

Various signs

To have relevant sign: this table inspired of the article published in the British Medical Journal summarizes the whole of the signs available within the framework of a tracking of the syndrome of Down. The markers in italic are in the course of evaluation.

Signs of the first quarter

Echography

This technique of evaluation of trisomy 21 (and others Aneuploïdie S) must much to the Professor K. Nicolaides of the Fetal Medicine Foundation of London.
the echographic marker used is the Clarté nucale. The measurement technique must answer strict criteria.
There exists another echographic marker but of more delicate measurement: the clean bone of the nose.

Biology

the substances used are free HCG and the DAD ( pregnancy-associated plasma protein has )

Signs of the second quarters

Echography

No echographic sign is symptomatic trisomy 21. However, one can sometimes highlight a certain number of minor or major anomalies which more frequently meet in this chromosomal disease.

minor Anomalies :

Hypoplasie or absence of the clean bones of the Nose,
short femur, lower than the 5th Centile for the age,
thickness of Nape of the neck higher than 6 mm at 20 weeks,
important spacing enters the first and the second Orteil,
brevity of the third phalange of the fifth Doigt,
language protruse…

major Anomalies :

of cardiac malformations (atrio-ventricular Channel in particular) and
of the digestive Sténose S (image in “double bubble” of sténose duodénale).

Biochemistry

The evaluation is made between 14+0 weeks of amenorrhoea and 17+6 weeks of amenorrhoea. The markers used are the Alpha-fœtoprotéine and free HCG. Certain laboratories add the Estriol plasma ticks but the addition of this third marker does not increase the sensitivity and is in fact little employed. This technique of evaluation by three serum markers names the Triple test. Certain laboratories balance the result according to the weight of the patient and/or the number of cigarettes fume per day.

Diagnosis

The diagnosis can be made only by the description of the Chromosome 21 additional by the Caryotype. In the first quarter by a taking away of Trophoblaste which is made as from 11 weeks up to 14 weeks. Beyond that, the iatrogenic risk of abortion increases in an important way. Before it is of 1% as for the amniocentèse. After one needs a puncture of Amniotic liquid to examine the cells of the fetus. When the date of confinement is close, it is necessary to carry out a puncture of fetal blood by puncturing the Umbilical cord because the realization of the chromosomic chart takes only a few days whereas it takes several weeks by the amniocentèse.

The genetic Council

Social life of the subject reached

The people reached of the syndrome have a life a little more difficult than the average: they are of course victims of their physical and intellectual delay, but more often still of the anxious or hostile glance that some relate to their anomaly which is however not contagious and which is more familiar and less despairing for the families that many affections congénitales.
the “trisomic ones” require to develop an emotional and sociable life, like each and everyone. It is necessary for the families to take the council of specialists who will help them to cause and to encourage intellectual and physical progress (muscular rehabilitation, adapted Physical-activities) of the subject.
Inter alia rules of communication, it is recommended to be expressed by clear and concise sentences, to answer the questions with relevance and with a time court.
As much as possible it is advised not to confine the trisomic children with the frequentation of a specialized milieu: many studies show that the contact of the school and “ordinary” children has an extremely positive influence on the general development and the Intelligence quotient of the subject reached of trisomy (IQ going from 20 to approximately 80, according to various parameters, in particular the intellectual stimulations offered by the environment).
On a long time hid in specialized places the children reached of the syndrome of Down. Their existence was then terrible and very short, their average life expectancy did not exceed adolescence. With a taking into account of their physiological insufficiencies and treating them like the thinking beings and magnets that they are, medicine manages today to give them an almost normal life expectancy and it is not rare that they take a place in the working life.

Trisomic 21 famous

Pascal Duquenne, actor, prize winner ( ex-æquo with Daniel Auteuil) of the price of male interpretation to the Cannes festival 1996 for its interpretation in the film the Eighth Day of Jaco Van Dormael.
Stephan Ginnsz, first trisomic actor to obtain, in 1995, the first role in a film entitled Duet , telling the history of a young trisomic boy in love with a violonist (Eden Riegel) and whose dream would be of being able one day to accompany it with the piano. Winner of the Price Martin Scorsese (1996), victorious of the Price Warner Bros Pictures (1996), Been included official with the 23e Academy Awards in the category student films (1996), finalist with the International film festival of Chicago for the children (1996), and nominated for a TASH Award (1997).
Chris Burke, known American actor to have played during four seasons, the role of Corky in the televised series Corky, a teenager not like the others (1989).
Émeline Dubois, raises Courses Rene Réaumur with Paris.
Nathalie Nechtschein, écrivaine and poet Frenchwoman, of which one of the text finds on the album They of Céline Dion.

Seek

Recent work reveals that the people carriers of trisomy 21 have a less activity of the gyrus toothed Hippocampe. This would be the physiopathological explanation of the variable deficiency of the memory of this subjects.

Surexprimés genes would be in question and in particular cystathionine beta synthase (CBS) and DYRK1A start to be recognized like two major targets by the international scientific community. Work to develop inhibiters of CBS and DYRK1A is in hand in France and abroad. To control the expression of these genes by the administration of these inhibiters would allow to increase way can be important the IQ from the trisomic 21 .

Others

Several sculptures of the Terrasse of the elephants to Angkor Thom would represent people having the morphotype trisomic 21.

Sources

References

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