The Patau Syndrome , including trisomy 13 , ( Syn. : Patau syndrome , Bartholin -Patau syndrome and D1 trisomy ) is a by tripling ( trisomy ) of genetic material of chromosome 13 caused disability based on a genome mutation . The syndrome is currently one of those chromosomal aberrations that are associated with above-average child mortality and the number of miscarriages and stillbirths .
History and discovery
The physical characteristics of children with this syndrome were first described in the medical literature in 1657 by the Dane Erasmus Bartholin . The German-American human geneticist Klaus Pätau discovered in 1960 that these are consequences of trisomy 13 . The name of the syndrome goes back to these two scientists, whereby the synonym Pätau syndrome is given quantitative preference over Bartholin-Pätau syndrome in the literature .
Frequency of occurrence
The Patau syndrome is one of the comparatively rare chromosome peculiarities and occurs on average in 1 in 15,000 to 1 in 4,000 children. This makes it the third most common trisomy among live-born children after trisomy 21 ( Down syndrome ) and trisomy 18 ( Edwards syndrome ).
The cause of the Patau syndrome is a chromosome peculiarity in which additional genetic material from chromosome 13 is present. The following types are distinguished:
- Free trisomy 13
- This most common form of the syndrome occurs when one of the germ cells contains an extra chromosome 13. This can happen if, during the formation of the egg cells or sperm cells, the chromosome pair 13 is not separated as usual and like the other chromosome pairs ( meiotic non-disjunction ). With a few exceptions, such an event occurs randomly. The frequency of occurrence of free trisomy 13 is associated with an increased age of the biological mother, although every woman of childbearing potential at any age can expect a child with trisomy 13. When free trisomy 13 is present, three instead of two chromosomes 13 are present in all body cells. The karyotype is therefore 47, XX, + 13 or 47, XY, + 13.
- Mosaic trisomy 13th
- In genetics, a mosaic is understood to mean the presence of several karyotypes within an organism. In mosaic trisomy 13, a trisome and a disome cell line coexist. The chromosome pairs stay together only during the first cell divisions after fertilization ( mitotic non-disjunction ). The later this process takes place, the fewer cells are trisome. Depending on the proportion of disome cells, the symptoms of Patau's syndrome are sometimes less pronounced. People with mosaic trisomy 13 have both body cells with 46 and body cells with 47 chromosomes. The karyotype is therefore 46XX / 47, XX, + 13 or 46XY / 47, XY, + 13.
- Partial trisomy 13
- In partial (= partial, partial) trisomy 13, chromosomes 13 are present in duplicate in all body cells, as usual, but part of one of the two chromosomes 13 is doubled, which means that one of chromosomes 13 is slightly longer than the other. The hereditary information in this section is therefore available three times. Usually, in people with partial trisomy 13, features of the syndrome are less pronounced, depending on the trisomal chromosome segment, although this should not be generalized, but always viewed on a case-by-case basis.
- Translocation trisomy 13
- In rare cases, the additional chromosome material from chromosome 13 has attached itself to another chromosome, usually to an acrocentric number 14, 15, 21 or 22. This change in location of chromosomes is called translocation in genetics , and the shape of trisomy 13 is accordingly Called translocation trisomy 13. The translocation chromosome is the product of a fusion (fusion) of the long arm of chromosome 13 and the long arm of one of the above acrocentric chromosomes. In exceptional cases the translocation chromosome consists of two long arms of chromosome 13. These types of translocation belong to the group of Robertson translocations . The karyotype of a translocation trisomy 13 is depending on which chromosome one of the number 13 has attached z. B. 46, XX, t (14; 13) or 46, XY, t (14; 13). Here the additional 13th chromosome has attached to one of the two chromosomes of number 14.
In translocation trisomy 13, one parent can be the "carrier" in some cases . A balanced translocation of a 13th chromosome can be detected in such a parent . The karyogram then 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 13. However, the likelihood that the person concerned will father a child with a translocation trisomy 13 is increased. If both chromosomes 13 have connected with each other in a balanced translocation in one of the parents, a child conceived by the person concerned always has a translocation trisomy 13/13. However, this is extremely rare.
With a few exceptions, signs of trisomy 13 always occur in combination with each other in a child, even if not all children show all characteristics at the same time or to the same extent.
Common features before birth
In the course of the steadily developing possibilities of prenatal examinations ( prenatal diagnosis ), some peculiarities have been documented over time, which can very often be detected in babies with Patau syndrome during pregnancy. Only in very rare exceptional cases are there any signs of trisomy 13 in the child during prenatal examinations. The indicators that can indicate the presence of a trisomy 13 in the unborn child, particularly in combination with one another , and which can sometimes be recognized by means of ultrasound or blood tests , include, for example:
- Heart defects (often left ventricular obstruction and Fallot's tetralogy as well as atrial septal defects or ventricular septal defects / in approx. 80% of children)
- sometimes dextrocardia (Greek dexios = right, kardia = heart), d. H. the heart is mirror-inverted and / or shifted to the right side of the chest
- White spots ( golf ball phenomenon in the heart) in approx. 35% of children
- a comparatively small baby (growth disorder / hypotrophic size, underweight )
- a comparatively small head ( microcephaly ) in approx. 12% of children
- Holoprosencephaly (developmental disorder of the forebrain and face ) due to an error in separating the brain into two hemispheres in approximately 40% of children
- Cleft lip and palate (often double-sided) in approx. 45% of children
- comparatively small eyes ( microphthalmia ), which are comparatively close together ( hypotelorism ), sometimes no eye primordia ( anophthalmia ) or monophthalmia .
- Underdevelopment or malformation of the nose and nostrils
- postaxial polydactyly (extra fingers or toes, often six instead of the usual five / hexadactyly )
- Bad posture and / or malformation of extremities , e.g. B. Radial aplasia
- a comparatively short thigh bone (femur)
- Ink eraser feet ( rocker bottom feet / innate flat feet with outwardly arched soles or with inward arched backs of the feet.)
- Sandal gap / sandal furrow (increased distance between the first and second toe )
- Malformations of the central nervous system (CNS) (e.g. spina bifida in different degrees)
- Bar agenesis (absence or severe underdevelopment of the corpus callosum , the connection between the two large halves of the brain )
- Enlargement of the Cisterna cerebellomedullaris / Cisterna magna in approx. 15% of the children (Cisterna cerebellomedullaris = CSF chamber on the neck side (= dorsal) between the cerebellum and the spinal cord ).
- a significantly increased concentration of the hormone alpha-1-fetoprotein ( alpha-feto-protein ) in the blood of the pregnant woman (as an indication of an open malformation of the central nervous system)
- Kidney malformations , polycystic kidney degeneration and other malformations in the urogenital tract in about 30% of children
- Omphalocele (= umbilical cord break: the umbilical cord on the baby is inflated like a bag and abdominal organs protrude through the navel) in less than 20% of children
- comparatively large amount of amniotic fluid ( polyhydramnios ) in approx. 15% of children, but sometimes also a comparatively small amount of amniotic fluid ( oligohydramnios )
- a noticeably large accumulation of fluid in the neck area of the unborn baby (high neck transparency )
- Hygroma colli in about 21% of children
Common features after childbirth
In many children, other peculiarities can be determined after birth. Not all children show all characteristics to the same extent. The most common features include:
- hypotrophic height and low birth weight ( small-for-gestational-age-baby / SGA-baby )
- Special features of the eyes : z. B. Tissue defects of the iris / iris or places where the iris or iris is "missing" ( coloboma ), defective development of the retina / retina , opacity of the eye lenses ( congenital cataract ), increased intraocular pressure ( glaucoma ), also persistent hyperplastic primary Vitreus
- large fontanel , scarred defect of the scalp along the sagittal suture ( aplasia cutis congenita ), trigonocephaly (triangular head shape due to a prominent, keel-like forehead)
- Hemangioma (blood sponge) on the upper lid of the eye, nevus flammeus (fire mark)
- Hearing loss or deafness
- specially shaped (dysplastic) and unusually deep-set ears
- Special features of the dermatoglyphs ( fingerprints ), four-finger furrow (in about 75 out of 100 children)
- unusually curved and narrow fingernails and toenails, missing fingernails and toenails
- Malformations of the digestive system (e.g. unusual arrangement of intestinal loops / malrotation , hyperplastic bile ducts )
- Special features of the genital organs, e.g. B .: testicles are not in the scrotum, urethra ends below / ventral to the usual mouth ( hypospadias ), urethra ends above / dorsal to the usual mouth ( epispadia ), malformation of the uterus
- Muscle weakness ( hypotonia )
- cerebral seizures ( epilepsy / frequent West syndrome )
- Sleep disorders, especially in children who are deaf and blind at the same time (due to problems finding the day-night rhythm).
Pätau syndrome can be suspected prenatally based on certain signs (see above ) and after birth (postnatal) based on external characteristics (suspected diagnosis). During pregnancy it is possible to diagnose trisomy 13 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 by an invasive (e.g. chorionic villus sampling or amniocentesis ) or non-invasive examination (using maternal blood). 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% reliable diagnosis after the birth. By chromosome analysis of lymphocytes of the blood not only the diagnosis can be confirmed, but also the type of trisomy 13 (Free trisomy 13, translocation trisomy 13, mosaic trisomy 13) are detected.
The following are to be distinguished:
- Edwards Syndrome
- Pseudotrisomy 13 Syndrome
- partial duplication 13q
- Smith-Lemli-Opitz syndrome
- Cerebro-Kosto-Mandibular Syndrome .
Trisomy 13 cannot be cured causally. Therapy is therefore limited to treating the individual physiological defects and other symptoms. This can be, for example, surgical interventions as well as therapeutic measures such as physiotherapy or speech therapy.
Many of the children affected die before they are born. Children who survive pregnancy and childbirth have so far mostly had a reduced life expectancy, although it has meanwhile been shown that the life span depends heavily on which peculiarities (especially in the physical-organic area) are present in them in which extent and whether they are after birth receive adequate medical and social treatment.
Most children who survive pregnancy and childbirth so far die in the first twelve months after birth. Girls often survive longer than boys: an average of 3 in 10 girls with trisomy 13 reach the age of five and 1 in 10 reach the age of ten, while boys generally do not survive the first five years after birth. The most common causes of death are heart failure, cardiovascular failure, respiratory failure and pneumonia.
In children with mosaic trisomy 13, the symptoms are usually less pronounced, depending on the proportion of disome cells, and their life expectancy is often positively influenced by this.
Trisomy 13 cannot be brought about by anything and is not causally curable. 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 13, the probability of having another child with Patau syndrome is slightly (1%) higher than the probability for her corresponding age group. The slight increase results in particular from the possibility of a mosaic in the parental germ cells, which cannot be ruled out .
The same applies to a translocation trisomy 13 if the chromosome findings of the parents are normal. However, there are indications of age dependency. If a balanced translocation of a 13th 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 13 in a child is 100% if the two chromosomes 13 of a pair are connected to one another in the balanced translocation of one parent (translocation 13/13). This is extremely rare.
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