Trisomy
Chromosomes are marvelous things! They carry in their genes the entire genetic code required to build a human being. Comprised of nucleic acid (DNA) and proteins, twenty-three pairs of chromosomes located in the cell nucleus are needed for the normal development of a human embryo. However, sometimes things go wrong. This paper will discuss some of the consequences of faulty chromosome separation during fertilization, resulting in Trisomy.
Trisomy is a chromosomal condition which occurs when three chromosomes, instead of the normal two are produced during cell division. This happens due to the failure of human chromosome pairs to separate normally during the process of meiosis (Hassold and Hunt, p. 281). After fertilization, the embryo will have an entire copy of the extra chromosome, and the trisomy is named for the number of the specific chromosome which was duplicated. Trisomies of both autosomal and sex chromosomes can occur, although the former condition has more severe consequences than the latter (Hassold and Hunt, p. 281).
Although trisomies can occur on any chromosome, the most common types of autosomal trisomies are Trisomy 21 (which causes Down Syndrome) and Trisomy 18 (which causes Edwards Syndrome), because embryos with trisomies on other chromosomes often do not survive to birth (Roubertoux & Kerdelhué, p.347). However, apart from the two conditions listed above, fetuses with other types of trisomies do survive to birth, although some may die soon after. Trisomy 8 (causing Warkany Syndrome 2), Trisomy 9 (Mosaic Syndrome) and Trisomy 13 (Patau Syndrome) all can potentially produce live births but Trisomy 22 frequently causes spontaneous abortion in the first trimester of pregnancy and live births are very rare (Hassold and Hunt, p. 283). Trisomy of sex chromosomes occur when an additional X or Y chromosome is added to the genotype during reproduction, and can result in the following syndromes: Triple-X Syndrome, where the female carries three copies of the X chromosome and no Y chromosome, Klinefelter Syndrome, where the male carries an extra X chromosome and XYY Syndrome, which is self-explanatory.
Although the causes of each type of trisomy are similar, the characteristics of each type of trisomy are very different and dependent upon the particular chromosome that is involved. The most well-known and understood condition, Trisomy 21, causes Down Syndrome. One of the most obvious physical characteristics of this condition is upwardly slanting eyes with small skin folds on the inner corners of the eyes. It was these characteristics that were the basis for the earlier name of “mongolism” for this condition (Roubertoux & Kerdelhué, p.347). Also apparent are flat facial features, a small nose and ears, low muscle tone and various other characteristics which are not so obvious. Up to fifty percent of people with Down Syndrome are born with heart problems, some of which are major and may cause their demise soon after birth. Other health problems for those born with this syndrome include endocrine problems, which can cause hypothyroidism, visual problems including crossed eyes, cataracts and nearsightedness, and hearing difficulties. People with Down Syndrome also have a much greater risk of contracting leukemia (Rabson, p. 6099) and Alzheimer’s disease, but their life expectancy is almost within normal range, many living into their seventies.
Unlike Down Syndrome, Trisomy 18, also known as Edwards Syndrome, manifests itself with a completely different set of problems. Exhibiting slow growth before birth and low birth weight, babies with Edwards Syndrome also display heart defects and abnormalities of other organs (Nelson, Hexem & Feudtner, pp. 873-874). Girls are more likely to survive than boys. Some of the physical characteristics present in Edwards Syndrome include a small and abnormally shaped head, a small mouth and jaw and clenched fists whose fingers overlap. Severe and life-threatening medical problems are common with this condition and as a result many Trisomy 18 children have a very short life expectancy, some not even surviving until birth and other dying within the first month of life. Severe intellectual disability is also a common trait of this condition (Nelson, Hexem & Feudtner, pp. 873-874).
The symptoms of children with Trisomy 8 (Warkany Syndrome) can vary greatly, with some children displaying no visible symptoms. If an embryo displays full Trisomy 8, where all the cells have the extra chromosome, this condition is usually fatal. However if partial Trisomy 8 is presented, where only some of the cells are affected, the person can usually live a full lifespan as long as inherent medical symptoms do not interfere. Due to this, the condition often goes undiagnosed. However, other cases display severe, highly visible symptoms which can include such things an elongated head with a large forehead, wide deep eyes and thick lips, and a long torso with narrow shoulders and hips. People with this condition also suffer from numerous medical issues such as spinal, bone and joint conditions, heart and kidney problems and underdeveloped genitals. In some cases, there can be a lack of intellectual development, but this is not true of every case.
Trisomy 9 is a very rare chromosomal disorder; however it does manifest some of the other symptoms of the disorders discussed above. Slow inter-uterine growth, mental retardation and heart problems are some of the symptoms of this disorder. Physical characteristics of those who suffer from Trisomy 9 include abnormalities of the face and skull, including a sloping forehead, short eyelids, a bulbous nose, slit-like nostrils, a small jaw and malformed ears. Many of these characteristics are seen in sufferers of other forms of trisomy. Together with the definitive physical characteristics, sufferers of Trisomy 9 are also likely to experience musculoskeletal, kidney and genital abnormalities (Hassold and Hunt, p. 289). Failure to thrive is often a key indicator of Trisomy 9. Some sufferers of Trisomy 9 are asymptomatic while others have difficulties with feeding, restricted growth, labored breading, profuse sweating and irritability. No study has been made on older sufferers of Trisomy 9, so no data regarding life expectancy is available.
Trisomy 13 is the most severe of all the conditions created by malfunction of chromosome division. Most of the children born with Trisomy 13 will die within the first twelve months of their lives, with at least half of those dying within the first month (Nelson, Hexem & Feudtner, pp. 873-874). Trisomy 13 indicates severe physical and intellectual retardation, and it appears to affect females slightly more than males. Similar to Trisomy 8, the range and severity of the symptoms is dependent upon the number and distribution of the cells which contain the extra copy of chromosome 13. The risk of having a child who suffers from Trisomy 13 increases with the age of the mother (Hassold and Hunt, p. 286)
Women who inherit three X chromosomes suffer from the genetic condition called Triple-X Syndrome. On rare occasions, some women may inherit more than one additional chromosome and their genotype can be XXXX or even XXXXX. Sometimes known as “superfemales”, they tend to be a little taller than average with very long legs and slender torsos. Their sexual development is usually normal and they are fertile, but can sometimes suffer from premature ovarian failure. Speech and language skill development is usually slightly delayed, but they fall within the range of normal intelligence.
Males with Klinefelter Sydrome have inherited one or more extra X chromosomes, leading to features which are feminizing (Maggi, pp. 111-113). In severe cases, these men may have breast enlargement, high pitched voices and little facial and body hair. These affects can be significantly diminished if they are treated with testosterone from puberty. Klinefelter Syndrome suffers tend to be taller than average and they typically have learning difficulties in childhood. Adults are sterile and have a higher than average risk of developing osteoporosis, diabetes and autoimmune disorders which are more commonly found in women. This is believed to be caused by low testosterone production (Maggi, pp. 111-113).
Like females who have inherited an additional X chromosome, males with an extra Y chromosome are classified as “super males”. Adults are usually tall and males with this condition are usually fertile. As adolescents, they are often slender, poorly coordinated and can suffer from severe facial acne. However, most live ordinary lives, unaware of their chromosomal abnormality (Maggi, pp. 111-113). There is some suggestion that men with this condition are more prone to violence due to the production of high levels of testosterone.
In conclusion, it can be seen that the condition of Trisomy can wreak chromosomal havoc in humans. The vast array of symptoms presented by these suffers can sometimes make diagnosis of their conditions difficult and genetic testing is often the only way to obtain a clear idea of which type of condition is occurring. Although some suffers of Trisomy do not survive, or live only a very short time, many live long and full lives, despite problems with intellect and learning, although the medical conditions inherent with Trisomy can often cause them to be under medical supervision throughout their lives.
References
Day, T. and Taylor, P.D. (1998). Chromosomal drive and the evolution of meiotic nondisjunction and trisomy in humans. PNAS. 95(5) 2361-2365
Hassold, T. and Hunt, P. (2001). To Err (Meiotically) is Human: The Genesis of Human Aneuploidy. Nature Reviews .Genetics, 2(4), 280-91
Maggi, M. SMIP - Sexual Medicine in Practice: Hormonal Therapy for Male Sexual Dysfunction (1). (2011). Hoboken, GB: Wiley-Blackwell.
Nelson, K.E., Hexem, K.R. and Feudtner, C. (2012, May). Inpatient Hospital Care of Children with Trisomy 13 and Trisomy 18 in the United States. Pediatrics. 129(5) 869-876
Rabson, A. B. (2010). Trisomy 21 leukemias: Finding the hits that matter. Oncogene, 29(46), 6099-6101
Roubertoux, P. L., & Kerdelhué, B. (2006). Trisomy 21: From chromosomes to mental retardation. Behavior Genetics. 36(3), 346-54.
