Patau syndrome

The Patau syndrome, also called trisomy 13, (syn.: Patau syndrome, Bartholin - Patau syndrome and trisomy D1 ) is one of the Tripling ( trisomy ) of genetic material of chromosome 13 caused disability on the basis of genome mutation. The syndrome is currently one of those chromosomal aberrations that are associated with a higher than average infant mortality and number of miscarriages and stillbirths.

History / discovery

The physical characteristics of children with this syndrome were described in 1657 for the first time by the Dane Erasmus Bartholin in the medical literature. The fact that these are consequences of trisomy 13, discovered in 1960 the German -American geneticist Klaus Patau. The naming of the syndrome is due to these two scientists, with the synonym Patau syndrome is given in the literature of quantitative preference to Bartholin's Patau syndrome.

Frequency of occurrence

The Patau syndrome is one of the comparatively rare chromosome characteristics and average occurs in 1 in 15,000 to 1 in 4000 children. This makes it among live-born children behind the trisomy 21 (Down syndrome) and trisomy 18 ( Edwards syndrome) is the third most common trisomy.

Causes

The cause of Patau syndrome is a chromosomal feature is present in the extra genetic material from chromosome 13. Differences are the following types:

In translocation trisomy 13 may be in some cases a parent " carriers / in ". In such a parent can be a balanced translocation of chromosome 13 detected. The karyotype then shows 45 instead of 46 individual chromosomes because two chromosomes have joined. Since this feature is omitted no relevant genetic or worse, the genetic information ( balanced =) in equilibrium, and there is no trisomy 13 with the person on. However, the likelihood is increased that the person in question bears witness to a child with a translocation trisomy 13. Have 13 connected with the balanced translocation in one parent both chromosomes together, a child conceived by the individual child always has a translocation trisomy 13 / 13th However, this occurs only very rarely.

Symptoms

Note sign on trisomy 13 come in a child with few exceptions always carried out in combination with each other, even if not all have children all the same features and in the same strong expression.

Common signs before birth (prenatal )

As part of the ever-evolving possibilities of prenatal tests ( prenatal diagnosis ) have been documented, which can very often be found with a Patau syndrome during pregnancy in babies with time some special features. Only in very rare cases can be found no features in the presence of trisomy 13 in a child with prenatal examinations. The Note characters together in the presence of trisomy 13 may indicate the unborn child, particularly in combination, and which are sometimes to be seen by ultrasound or blood tests include, for example:

• Heart failure ( left ventricular obstruction, and frequently the tetralogy of Fallot and atrial septal defects or ventricular septal defects / at about 80 % of children )

• Sometimes dextrocardia ( gr dexios = right, kardia = heart ), ie the heart is a mirror image created and / or shifted to the right chest

• White spots ( golf ball phenomenon in the heart) at about 35 % of children

• A comparatively small baby (growth fault / hypotrophic size, underweight )

• A comparatively small head ( microcephaly ) at about 12% of children

• Holoprosencephaly ( developmental disorder of the forebrain and the face) because of an error in the separation of the brain into two hemispheres at about 40 % of children

• Cleft lip and palate (often double-sided) at about 45 % of children

• Comparatively small eyes ( microphthalmia ), which are relatively close to each other ( hypotelorism ), partly no eyes plant ( anophthalmia ) or Monophthalmie.

• Underdevelopment or malformation of the nose and nostrils

• Axial polydactyly ( extra fingers or toes, often six instead of the usual five / hexadactyly )

• Poor posture and / or malformation of extremities

• A comparatively short thigh bone ( femur)

• Erasers feet ( rocker bottom feet / congenital flat feet with. Outwardly curved shape of the sole or dorsum of the foot with curved inwards

• Gap sandals / sandals furrow ( increased distance between the respective first and second toe )

• Malformations of the central nervous system (CNS ) (eg, spina bifida in varying degrees )

• The corpus callosum (absence or severe underdevelopment of the corpus callosum, the connection between the two great halves of the brain )

• Enlargement of the cisterna cerebellomedullary / cisterna magna at about 15% of children ( Cisterna located cerebellomedullary = Liquorkammer neck side ( = dorsal) between the cerebellum and the spinal cord.

• A significantly increased concentration of the hormone alpha -1 -fetoprotein (alpha - fetoprotein ) in the blood of pregnant women ( as an indication of an open malformation of the central nervous system )

• Renal anomalies, polycystic kidney disease and other malformations in the urogenital tract in about 30% of the children

• Omphalocele ( umbilical cord = break: The umbilical cord to the baby is bloated baggy and abdominal organs emerge through the navel ) at less than 20% of children

• Comparatively large amount of amniotic fluid ( polyhydramnios ) in about 15 % of the children, but partly also comparatively small amount of amniotic fluid ( oligohydramnios )

• A strikingly large accumulation of fluid in the neck region of the unborn baby (large nuchal translucency )

• Hygroma colli at about 21 % of children

Common signs after birth ( postnatal)

In many children, more features can be detected after birth. Not all children have all features in the same expression. The most common features include:

• Hypotrophic size and low birth weight ( small- for- gestational -age baby / SGA baby)

• Special features of the eyes: eg tissue defects of the iris / iris or places at which the iris or iris " missing" ( coloboma ), defective development of the retina / retinal clouding of the eye lenses ( cataracts), increased intraocular pressure ( glaucoma)

• Fontanelle, scarred defect of the scalp ( scalp ) along the sagittal suture, trigonocephaly ( triangular head shape by a promintente, keel -like forehead

• Hemangioma ( strawberry mark ) on the upper eyelid of the eye, nevus flammeus ( port-wine stain )

• Blindness

• Specially formed ( dysplastic ) and unusually low-set ears (left)

• Hearing impairment or deafness

• Special features of dermatoglyphics (fingerprints), simian crease ( about 75 out of 100 children / right)

• Unusually curved and narrow fingernails and toenails, missing finger and toe nails

• Malformations of the digestive system (eg unusual arrangement of loops of bowel / intestinal malrotation, hyperplastic bile ducts )

• Special features of the reproductive organs, such as: testicles are not in the scrotum, urethra ends below / ventral to the usual discharge point ( hypospadias ), urethra ends above / dorsal to the usual discharge point ( epispadias ), malformation of the uterus

• Muscle weakness ( hypotonia )

• Seizures (epilepsy / heaped West syndrome )

• Sleep disorders, especially in children who are deaf and blind at the same time (for problems to find the day-night rhythm).

Diagnosis

The Patau syndrome can be prenatally (prenatal ) by particular flag ( see above) and after birth ( postnatal) suspected because of external characteristics ( diagnosis ). During pregnancy, there is a possibility that trisomy 13 to diagnose or eliminate the unborn child by chromosomal analysis with high security. The required material for this analysis must contain cells of the fetus and is an invasive investigation collected (eg, chorionic villus sampling or amniocentesis ). Prenatal chromosome analysis is in Germany all the women must be offered openly and women aged 35 years.

For almost 100 percent reliable diagnosis after birth, a chromosome analysis must connect. By chromosome analysis of lymphocytes in 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.

Treatment

Trisomy 13 is not incurable. Therefore, the therapy is limited to treatment of the individual physiological defects and otherwise symptoms. This may, for example, surgical procedures, as well as acting therapeutic measures such as physical therapy or speech therapy.

Forecast

Many of the affected children die before birth. Children who survive pregnancy and childbirth, have been mostly a reduced life expectancy, wherein it has now shown that the lifetime strongly depends on which features ( in physical- organic region in particular ) applicable to them in which form and whether they after the birth be treated medically and socially adequate.

Most children who survive pregnancy and childbirth, dying so far during the first twelve months after the birth. The prognosis is more favorable for girls than for boys: Average 3 out of 10 girls with trisomy 13 reach the fifth and one tenth year of 10, while boys do not usually 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 depend on the proportion of disomic cells usually less pronounced and their life expectancy is further often positively influenced.

Repetition probability

Trisomy 13 can be brought about by anything and is not incurable. A general prophylaxis (prevention) is not possible. With the option of (late) abortion for medical reasons, the live birth of the child can be prevented by the secured prenatal diagnosis at best. For a woman who was already pregnant with a child with Free trisomy 13, is the chance to get again a child with Patau syndrome, low ( 1%) on the probability of their appropriate age group. The small increase is due particularly to the possibility can not be excluded a mosaic in the parental germ cells.

Similarly with a translocation trisomy 13 when the chromosome analysis of the parents is unremarkable. However, there is evidence of age dependence. If one parent a balanced translocation of chromosome 13 detected, the probability of children lies with the translocation type of syndrome theory at 25 %. Experience values ​​are well below that, as often early and often unnoticed by the pregnant woman dies in chromosomal Inbalance the fetus. However, the probability for trisomy 13 in the child 100% when in balanced translocation of a parent, the two chromosomes 13 are a pair of interconnected ( translocation 13/13). This is extremely rare.