Patau syndrome or Trisomy 13 syndrome is the least common yet the most severe of all the viable autosomal trisomies; median survival is reported to be fewer than 3 days (Jonathan P Wyllie et al., 1994). This syndrome was first brought to the attention of the medical community in 1960's and was labeled as a cytogenetic syndrome. The cause of Patau syndrome is the addition of an extra copy of chromosome 13 in the form of an acrocentric chromosome of a medium-length. The presence of this extra copy of chromosome 13 will disturbs the normal course of development of the fetus resulting in the characteristic features of this syndrome (Philippe Moerman et al., 1988).
Patau Syndrome is not considered as an inherited disorder, but rather it develops as a result of random events during the process in which reproductive cells - as in the sperm and egg - are developed. Throught the process of cell division non-disjunction will occur resulting in faulty reproductive cell carrying an extra chromosome (S. Shikiriyama et al., 1984). In this case, an additional copy of chromosome 13 will be present in the egg or sperm. If any of these defected cells are used in fertilization, then the developing fetus will carry the extra copy of chromosome 13 in it genetic makeup and thus in all of its cells.
Mosaic Patau syndrome is another variation of the syndrome, which is also not governed by the rules of genetic inheritance. This version of the syndrome is similarly the result of a random process that happen in cell division (S. Shikiriyama et al., 1984). However in this case, some cells will express the normal number of chromosome 13 - being 2 - while others will display three copies of the chromosome. The severity of the disease will depend upon the number and type of cells in which the non-disjunction of chromosome 13 is manifested at.
Patau syndrome due to a translocation, on the other hand, can be a indeed, influence by inheritance's laws. Approximately 20% of cases are attributed to an unbalanced chromosomal translocation (Wyllie JP et al., 1994). This situation is usually induced by a Robertsoian chromosome translocation which usually happens between chromosome 13 and 14. Clinically, this translocation is indistinguishable from the non-disjunction form. If one parent carries a Robertsonian translocation involving chromosome 13, then the recurrence risk of the disorder would be significantly increased compared to non-disjunction.
Physiology and Pathology
Trisomy 13 has a tremendous impact upon the development of the embryo. Its influence can be seen through complex alteration to the various physiologic structures ranging from the Central Nervous to the circulation system.
Newborns with Patau syndrome are typically assigned low Apgar scores (it is a scale used to quickly assess the health of a newborn). These newborns usually present with various malformed structures. Some affect the face as in Cleft lip, Cleft palate. Others affect the skull as in Microcephaly and various Scalp defects. Rocker bottom feet and hernias are also common findings (A.C. Duarte et al., 2004).
In 80% of cases, physical symptoms include Cardiac defects accompanied by series of other complications (A.C. Duarte et al., 2004). These conditions denerally include some form of atrial and/or ventricular septal defects(L. J. Butler et al., 1973). One of the most common and debilitating symptoms is Holoprosencephaly. Holoprosencephaly, a high frequency defect with this syndrome, is caused when the development of the brain is impeded preventing the formation of a distinct left and right halves of the brain. The presence of facial malformations centered in the midline of the face - as in malformed nose, absence of an eye or sever clef lip is generally indicative of Holoprosencephaly (Philippe Moerman et al., 1988). Furthermore, renal malformations, including polycystic kidneys can also be present (Wyllie JP et al., 1994). Chronic mental deficiency is the most widely present feature in a person expressing Patau Syndrome. It is relatively easy to diagnose Patau syndrome at the time of birth due to the presence of structural birth defects and a poor neurological performance. The probability ratio is generally reported to be around 1:5000 in every live birth (Wyllie JP et al., 1994).
Gene(s) responsible or implicated in the disorder
Patau syndrome is caused by the addition of an extra copy of chromosome 13 during conception. It seems that the exact mechanisms by which chromosomal trisomies interfere with fetus development are still unclear. Scientist are trying to use trisomy 21 as a model system to understand and study autosomal trisomies(S. Shikiriyama et al., 1984).
Normal development requires the presence of 2 copies of the human autosomal genome. If a third copy of the gene is found, in most cases, it will lead to the death of the developing fetus. Trisomy 13 is unique in the regard that it is one of very few autosomal trisomies that can allow development to proceed and thus results in live birth (Wyllie JP et al., 1994). It seems that the development of CNS structures and the heart are especially perceptive to chromosomal imbalance. This can be influenced either by the individual genes actions or by the destabilization of the developmental process involving gene cascade (Philippe Moerman et al., 1988).
Population genetics
Incidence of Patau syndrome is reported to be around 1 case per 5,000-6,000 live births (Wyllie JP et al., 1994). There does not seem to be racial or geographic factors that influence it frequency. However, there seem to be a strong correlation between Patau syndrome and an increased maternal age; this fact seemed to be shared across all autosomal trisomies (L. J. Butler et al., 1973). Children with Patau syndrome have a mean survival of 2.5 days, with only one in 20 children surviving past the 6 months mark (Wyllie JP et al., 1994). However, there are records of children survive into their teens and they actually seem to perform better than one might expect considering their disabilities. Nevertheless, it is rare for children with Patau syndrome to survive past adulthood (L. J. Butler et al., 1973). Curiously, the sex ratio at birth is slightly skewed toward females. This observation could be the results of the higher mortality rate among the males; thus it is normal to have a continuously skewing ratio toward females as these children age (Wyllie JP et al., 1994).
Clinical features
Patau syndrome is developed in the prenatal period and is fully evident at birth. A significant number of cases of chromosome 13 trisomy will end in a spontaneous abortion, or stillbirth (A.C. Duarte et al., 2004). Furthermore, mortality rate is quite high among neonates. Developmental delays will be continually expresses through the children lives. This decline reflects a worsening developmental lag compared with normal children. In a case study of 21 patients who survived past their 5 year birthday with Patau syndrome , - 18 had nonmosaic and 3had the mosaic form -the oldest lived only till 21 years of age (Wyllie JP et al., 1994).
There are a wide spectrum of possible clinical features with this syndrome; however, severe mental deficiency is a consistent feature in children born with Patau syndrome (S. Shikiriyama et al., 1984). Holoprosencephaly ( fused brain), polydactyly ( extra digits), flexion of the fingers, rocker-bottom feet, clef palate, neural tube defects, and heart defects are also frequent clinical features (Philippe Moerman et al., 1988). Serious cardiac anomalies are generally present. The most common causes of death are generally cardiopulmonary arrest (68%), congenital heart disease, followed by pneumonia (Philippe Moerman et al., 1988).
As mentioned earlier, survivors with Patau syndrome will have severe mental retardation, developmental delays and are usually at a higher risk for malignancy. For infants surviving the neonatal period, an average stay in a neonatal ICU is usually arround 10.8 days (Philippe Moerman et al., 1988).
Pathogenesis (if known)
Although specific etiologic factors have not been identified yet, a significant association is recognized between Patau syndrome and increased maternal age. It seems that the older the mother the higher the chances of aneuploidy to result from nondisjunction during the maternal meiosis I (L. J. Butler et al., 1973).
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Unfortunately there is no cure to Patau Syndrome. A successful treatment regiment will deed to focus on the particular physical problems expressed by each child. Many of the newborns will have difficult time surviving the first couple of days or weeks because of the complex heart defects and/or severe neurological problems. Diagnosis is usually confirmed by Gastrointestinal x-rays or ultrasound to reveal abnormal rotation of the internal organs.MRI or CT scans of the head are used to verify the diagnosis of holoprosencephaly. Chromosome studies can be gone to diagnose trisomy vs. translocation.
Surgery may be necessary in order to address the cardiovascular defects or the facial deformities - as in cleft lip/palate. A regiment of physical, and speech therapy should be implemented to help individuals with Patau syndrome reach their full possible potential. It is also advised that parents of a Patau syndrome child should receive genetic counseling to determine their risk of having another child with the syndrome.
