Down syndrome is the most common and best known chromosomal disorder in humans. It is typically associated with mental retardation, developmental delays and a particular set of facial characteristics. The three genetic variations that can cause Down syndrome include: Trisomy 21, mosaic Down syndrome and translocation Down syndrome.
The trisomy of chromosome 21 will affect almost every organ system in the body, with a wide range of phenotypic effects, although as mentioned earlier, not all cases of Down syndrome will present with the same phenotype. In all cases of Down syndrome there is a level of cognitive impairment, as well as the characteristic craniofacial features, such as an anteriorly and posteriorly flattened head, dysplastic low-set ears, small nose, depressed nasal bridge, protruding tongue, high-arched palate, dental abnormalities, and a short and broad neck. Further affects of the congenital disorder include, congenital heart disease, skeletal and bone abnormalities, compromised immune systems, hearing defects, increased predisposition to respiratory infections and increased chance of childhood leukemia .
Babies born with Down syndrome often have short arms and legs with lower than normal muscle tone, which makes it difficult for them to develop movement. Normal developmental milestones like standing, walking and reaching, often come later than for other children. In addition, 50% of all patients with Down syndrome will have problems with their sight and hearing. Otitis media with effusion is a common problem, which is a build up of fluid in the middle ear that may thicken causing sound to be muffled and distorted. Common eye problems include, a squint or lazy eye, short-sightedness, recurring eye infections and cataracts.
Approximately 1 in 10 patients affected with Down syndrome have issues with their thyroid gland, usually hypothyroidism. Symptoms of an under active thyroid include, lethargy, weight gain and slow reactions, both physical and mental. In more rare cases, Down syndrome patients may be affected with hyperthyroidism, symptoms of which include breathing and sleeping difficulties, and hyperactivity.
Antenatal screening for Down syndrome was first developed in the 1970s using previous history of congenital disorders and advanced maternal age. Things moved on in the 1980s when it was discovered that there was an association with Down syndrome and abnormal levels of serum markers, such as alpha fetoprotein and human chorionic gonadotrophin. Maternal serum screening further improved the detection rate of Down syndrome .
Recently, the ultrasound has become an extremely useful tool for screening for Down syndrome, which offers a number of advantages. The condition can be detected in the first trimester via fetal nechal translucency thickness; by accurately dating the pregnancy there can be a more precise evaluation or serum screening; and an ultrasound in the second trimester can reveal minor and major structural abnormalities characteristic of the condition .
Screening for trisomy at chromosome 21 should be an option for all women as part of their routine antenatal care, being fully informed of the implications and limitations of the screening methods. Women deemed in the high risk group following screening, should then be offered diagnostic testing to determine if their foetus is affected by trisomy 21. Since invasive prenatal diagnosis has around a 1% risk of miscarriage, information gained from the various screening techniques is combined with maternal age to greatly lower the number of false positive rate and therefore reduce the need for unnecessary invasive testing .
Treatment depends on the organ systems involved.
Over the past 50 years the prognosis of people with Down syndrome has greatly improved, with individuals being healthier, well integrated into society with jobs and social lives, and have improved life expectancies. However, compared to non-Down patients their life expectancy is still reduced. Studies have shown that 1 year survival rates for infants with Down syndrome increased from 60% in the 1940's to over 90% in the 1980s . A study of 389 Down syndrome infants between 1980 and 1989 showed that survival rate were 88% at 1 year and 82% at 10 years. There was a reduced survival rate in patients with congenital heart defects, which was at 72% at 10 years, with pneumonia often being a complication. Information in the cause of death were obtained for 55 of the 63 (87%) deaths, which are as follows:
The life expectancy of those with Down syndrome has greatly improved in the last 100 years. For example in Australia the average life expectancy has gone from 18 years in 1963 to 60 years in 2002 . For those reaching their sixth decade, their longer lifespan is associated with better cognitive functioning .
With longer life spans and improved prognosis, patients with Down syndrome can now live a relatively long and fulfilled life. With medical management, early intervention, an appropriate home environment, education and vocational training, the cognitive level of functioning of Down syndrome children and adolescents is improved, greatly helping with the transition into adulthood12. Patients should be actively encouraged to develop a level of independence and participate in recreational and social activities.
Down Syndrome is caused by one of three chromosomal anomalies. The majority of cases, around 88%, is caused by full trisomy at chromosome 21. Chromosomal translocation is the cause in approximately 4.5% of cases, with the remaining 7.5% of cases being the result of mosaic trisomy .
In approximately 79.5% of cases the chromosomal abnormality is maternal and the remaining 20.5% is paternal . The abnormality is most likely to occur during the first meiotic division, occurring 3 times as often than meiosis II errors.
Many studies have been conducted over the last century to determine the prevalence of Down syndrome, due to its clinical significance. In the most general terms it is estimated that Down syndrome occurs in 1 of 732 births in the United States, although this may vary with maternal age and different ethnic groups .
Some evidence has suggested that there is an increased prevalence of Down syndrome in infants of Hispanic mothers when compared to non-Hispanic white mothers and African American or African mothers . However, it is important to note that these variations in prevalence could be influenced by factors affecting the level of healthcare, such as prenatal care and diagnosis, or selective termination .
The age of the mother can also affect the prevalence of Down Syndrome, in fact the most important risk factor for Down syndrome is advanced maternal age . There is no significant affect on parental age until it reaches 35 years or older and the risk is at its greatest when the maternal age is 40 years or older .
Animal models have proved extremely useful in determining a genetic model for Down syndrome. A popular hypotheses for the abnormal gene mechanism is the gene-dosage hypothesis, where having three copies of the same gene expressed, results in the phenotypes of Down syndrome . It can be explained as a threshold effect – the amount of protein produced from the transcription of the three alleles, has to reach a certain level before the phenotype manifests. If the threshold is not reached then the associate phenotype does not present. This helps to explain why some Down syndrome patients have different phenotypes to others .
There are no guidelines for prevention of Down Syndrome.
The most common and well known chromosomal disorder in humans, Down syndrome, is caused by a trisomy at Chromosome 21 . It is a major cause of mental retardation and congenital heart disease and is characterised by dysmorphic body and facial features, problems with the endocrine, immune and digestive systems, as well as an increased risk of developing dementia and leukemia .
However, it is important to note that the phenotypic expression of Down syndrome is not the same in each patient, for example there is a congenital heart defect in only 40% of Down syndrome patients .
Down syndrome is the result of an extra chromosome 21 i.e. three chromosomes instead of the usual two. The biggest risk factor is an advanced age of the mother, with those over 40 having the highest risk of having a child affected with Down syndrome. In general the condition occurs in approximately 1 in 750 births and can be detected by a number of antenatal screening methods, including ultrasound and maternal blood serum analysis.
The extra chromosome 21 affects every organ system in the body and is characterised primarily with mental retardation and recognisable facial features. Not all cases of Down syndrome are the same, some patients will have different presentations to others. Other affects of the extra chromosomes include, heart disease, skeletal abnormalities, problems with the immune system, hearing difficulties and an increased chance of developing a childhood leukaemia.
Over the past 50 years the prognosis in those with Down syndrome has greatly improved, with it not being unusual for a patient to live into their sixth decade.