Patau Syndrome

2024 Author: Josephine Shorter | [email protected]. Last modified: 2024-01-07 17:49

Content:

Symptoms of Patau Syndrome

Causes of Patau syndrome

Diagnostics of the Patau syndrome

Treatment of Patau syndrome

Patau syndrome is one of the long-established and studied chromosomal diseases. Back in 1657, the symptoms of this disease were described by Erasmus Bartholin, although it was not until 1960 that it was possible to prove that it was provoked by a genetic defect from Dr. Klaus Patau, after whom it got its name. Interestingly, frequent cases of Patau syndrome were observed among the inhabitants of the tribes from the Pacific Islands, which gave reason to believe that the main cause of the disease was radiation, which was widespread in that area as a result of field tests of atomic bombs.

Normally, the human chromosome set contains 44 homologous (paired) and two sex chromosomes. For various reasons, in very rare cases, errors are possible when the chromosomes diverge during the division of the embryonic cells, due to which aneuploidy occurs - a change in the karyotype. The case when an additional chromosome is synthesized is defined as trisomy.

In essence, Patau syndrome is a pathological condition of the human genome, in which an extra thirteenth chromosome is found. In this regard, the disease received the scientific name trisomy 13. The frequency of this pathology reaches 1: 7000, but usually this figure fluctuates in the region of 1: 10000-1: 14000. The sex ratio of patients with trisomy 13 chromosome is approximately 1: 1. A characteristic feature of newborns with this disease is true prenatal hypoplasia in 25-30%, which manifests itself during normal pregnancy (without minor prematurity).

The structure of trisomy 13 consists of a variety of developmental defects:

Central nervous system - microcephaly, holoproencephaly (defects of the hemispheres at the stage of formation), meningomyelocele of the spinal cord, deficiencies in motor and mental development;
Peripheral nervous system and sensory organs - microphthalmia, cataracts, deformation of the auricles;
Musculoskeletal system and skin - extra fingers, umbilical hernia (omphalocele), cleft upper lip (cleft lip) and palate (up to the cleft palate), protruding heel, no skin or hair (most often eyebrows);
Heart - congenital heart disease (defect of the interventricular septum);
Genitourinary organs - kidney pathology and abnormal development of the genital organs.

To reliably determine the presence of Patau syndrome before the birth of a child, prenatal screening is performed, and after birth, a karyotype analysis is performed.

Genetic details

Basically, there are two genetic forms of trisomy on the thirteenth chromosome:

Simple trisomy - three chromosomes of the same species exist freely and realize their genetic potential.
Robertsonian translocation - two chromosomes remain free, and the third is fused by long arms with another acrocentric chromosome (for example, from 14 or 21). Since the acrocentric chromosomes in short arms have only rRNA genes duplicated many times in the karyotype, their functionality is preserved in most cases.

In any case, the karyotype of a patient with Patau syndrome is determined by the formula 47 XX (XY) 13+. Cases of non-Robertsonian translocations, isochromosomal and mosaic forms of trisomy 13 are sometimes recorded.

The pathological picture and symptomatology in the genetic varieties of Patau syndrome does not differ. In 3/4 of patients, an extra 13 chromosome is found, the remaining quarter of patients suffer from the involvement of 13 pairs of chromosomes in the translocation, which in 75% of cases is due to the denovo mutation (a new one that has arisen on its own) - the so-called "genetic error". Studies of the inheritance of Patau syndrome show that the remaining 25% of cases of trisomy 13 are due to the transfer of translocalized chromosome thirteen from one of the parents. In this case, the risk of recurrence in the next child (recurrent risk) is 14%.

Symptoms of Patau Syndrome

Patau syndrome has many characteristics that appear before and after childbirth:

In half of the cases, a pregnancy complication such as polyhydramnios is recorded - an excess of the amount of amniotic fluid in the amniotic cavity, characteristic for a certain period of pregnancy. It is determined by the amniotic fluid index, calculated during an ultrasound examination of the fetus.
Newborn babies with trisomy 13 have an underestimated body weight of about 2.5 kg.
Defects indicating insufficient formation of the cardiovascular system: atrial or interventricular septal defect, vascular transposition, one umbilical artery, are present in 80% of patients.
The widest list of defects is recorded on the part of the musculoskeletal system and the musculoskeletal system: a sloping and lowered forehead, narrowing of the orbits and a decrease in the distance between them, retraction of the bridge of the nose, widening of the nose at the base, deformation of the auricles, cleft lip, cleft palate, cleft palate, extra fingers and toes, shortened neck, umbilical hernias.
Ophthalmic pathologies are also common: corneal opacity, congenital coloboma (splitting of the lens, retina, optic nerve, choroid, crystalline, or eyelid), which occurs due to improper closure of the optic cup slit, microphthalmia (congenital reduction of the eyeball).
In some organs of the digestive system, severe pathological processes occur: fibrocystic formations in the pancreas, the development of excess spleens.
From the genitourinary system, the genitals and kidneys are affected. The size of the kidneys exceeds the norm, cysts form in their cortical tissue, and the bodies of the organs are too divided into lobes. The genitals are abnormally enlarged or deformed.
Severe mental and motor developmental retardation is characteristic of all surviving children with complete Patau syndrome - their condition is characterized as idiocy. This is accompanied by such pathologies of the development of the central nervous system as microcephaly (underdevelopment of the brain) and holoproencephaly (disorders of the formation of the cerebral hemispheres).

In some cases, there is a coincidence of some of the symptoms of Patau syndrome with other congenital malformations characteristic of a number of diseases, for example, Mohr and Meckel syndromes or Opitz trigonocephaly. To correctly, accurately and reliably determine the disease, it is necessary to study the karyotype. Even if the pregnancy is terminated surgically or the child died within a short time, it is imperative to carry out a cytogenetic diagnosis of chromosomal disease, which is necessary to warn parents about the danger and determine its probability.

Causes of Patau syndrome

The main reason for all the above destructive features of insufficient fetal development is the third thirteenth chromosome. It is assumed that, being an extra copy, it makes it difficult for cells to read the genome, which interferes with the normal formation of tissues and the timely completion of their growth and development.

Studies of the exact reasons for the nondisjunction of the thirteenth chromosome in meiosis have not been carried out, since this requires the organization of a large-scale collection of data for all cases and comparison with various data on the putative factors affecting the genome. The situation is also complicated by the fact that it is not known for certain when exactly the aforementioned failure occurs - at the stage of formation of germ cells or during the formation of a zygote. Simpler analyzes of these anamnesis allowed scientists to conclude that the chance of developing trisomy 13 with age of the mother increases, although this relationship is less significant than the proven relationship of the occurrence of Down syndrome.

It is assumed that Patau syndrome can be triggered by ionized radiation, infectious diseases, the influence of various toxicants, poor environmental conditions and even bad habits.

Many scientists argue that the above-described mutation of a sex or germ cell occurs by chance, like many other denovo mutations, to which every person is susceptible. It follows from this that Patau syndrome is a natural deviation for each type, which with an insignificant probability can occur with any person.

This can be said of complete trisomy 13, but the balanced translocation form of the disease is hereditary. It can occur in a child with a small probability, or it can be inherited without the manifestation of the syndrome, since the "extra third" chromosome 13 in this case is associated with another chromosome and is a danger only for the next generation.

Diagnostics of the Patau syndrome

To confirm or refute the suspicion of trisomy 13, as in the case of other genetic diseases of the embryo (Edwards, Down syndromes, etc.), it is necessary to undergo screening.

Diagnostics begins with an ultrasound examination and analysis of special biochemical markers, which make it possible to roughly calculate the risk of the disease in the child of the examined woman.

According to the results of the first stage, the expectant mother can be attributed to the risk group.

In this case, prenatal diagnosis is carried out using invasive methods:

At 8-12 weeks - a biopsy of the chorionic villi;
At 14-18 weeks - amniocentesis;
After the twentieth week - cordocentesis.

The obtained samples from biological materials of the fetus are subjected to operations to search for trisomy of the thirteenth chromosome using karyotype analysis by differential staining of chromosomes or PCR diagnostics.

If the specialist did not find reasons for additional examinations on the ultrasound, and prenatal diagnosis was not carried out, the neonatologist can determine the genetic abnormality in the infant due to clinical symptoms and dermatographic changes. However, only the analysis of the karyotype can be the basis for confirming the diagnosis of trisomy on the thirteenth chromosome.

Treatment of Patau syndrome

It is impossible to correct chromosomal abnormalities. The complex work of a group of different specialists is to constantly monitor the patient's health and support the family. At the moment, medicine does not have the means that can influence the body at the genetic level, and chromosomal abnormalities in Patau syndrome affect most cells.

In general, the prognosis for people with Patau syndrome is disappointing - less than 15% live up to the age of five, and in countries with a high level of health care system 2-3% of patients live up to the age of ten. At the same time, children need constant care and, even in the absence of fatal organ damage, suffer from mental disability and will never be able to socially adapt and take care of themselves on their own.

There is no chance of recovery, the only thing that can be done for the patient is to improve his living conditions, to correct his condition and associated pathologies. Children with this disease should be constantly examined by a pediatrician, neurologist, ophthalmologist, geneticist, otolaryngologist and other specialists. Surgical intervention to correct pathologies of the heart, kidneys and abdominal organs is performed according to the indications of a general surgeon.

Thus, maintaining the viability of a patient with Patau syndrome is impossible without the participation of several specialists and their interaction, since chromosomal abnormalities can affect different organs and systems and disrupt their work.