Down syndrome also known as trisomy 21 is the most common autosomal disorder occurring at a frequency of one in eight hundred to thousand newborns. This syndrome is named after the scientist Dr. John Langdon down who described its features in 1862 AD. It is caused by an error in cell division which results in an extra 21st chromosome. This error may be paternal or maternal in origin. However, the maternal origin is more common. The risk of Down syndrome increases with the maternal age, i.e. from about 0.1% in women of age 20 to about 3% in women at or above 45 years of age. Parents of individuals suffering from down syndrome are genetically normal.
Mother of age 45yrs of age is more likely to give birth to babies with Down syndrome due to exposure of the oocyte to the harmful environmental factors for long periods of time as graffian follicles are present in fetal life and it continues to exist through the reproductive life of the female while make sperms have short lifespan and is highly unlikely to harmful environmental exposure. Down syndrome is neither autosomal dominant nor autosomal resistant because it is just an error in the translation process of chromosome 21.
Karyotypic features of Down syndrome
- Trisomy – 21 type
About 90% of cases have completed extra chromosome 21 (47, XY + 21)
- A translocation variant (also known as Robertsonian translocation)
It makes up 4% of all cases. It has extra chromosomal material derived from the inheritance of parenteral chromosome bearing a translocation of the long arm of chromosome 21 to chromosome 22 or 24.
- Mosaic variant
It occurs in about 1% of all cases. It is caused by the mitotic non-disjunction during embryogenesis. They have a mixture of cells with normal chromosomes and cells with extra chromosome 21.
Clinical features of Down syndrome
Patients with Down syndrome have physical and mental retardation. It is the most common cause of genetic mental retardation. Physical features includes broad, flat face, slanting of eyes, epicanthic fold, short nose, oblique palpebral fissure when the eyes are open, flat nasal bridge, flat back of head, single palmar crease or simian crease, many loops on fingertips, special skin ridges, clinodactyly, small and arched palate, big and wrinkled tongue, dental abnormalities etc. There are many associated abnormalities in Down syndrome such as heart disease, hearing problems, vision problem etc. which are described below:
- Congenital heart disease
In about 30 – 40% of patient, congenital heart disease is present. Among these, endocardial cushion defect accounts for 40 – 60% of cases. Endocardial cushion defect if present, may lead to the formation of the arterioventricular canal. Arterioventricular canal is the common connection between the 4 chambers of the heart. Cardiac evaluation should be done by the age of nine months, as it is the most significant factor in determining the life expectancy in Down syndrome. Atrial and ventricular septal defect along with arterial – ventricular malformation is responsible for the majority of the deaths in infancy and childhood.
- Gastrointestinal malformation
Duodenal atresia is present in about 12 % of the patient with Down syndrome. Increased risk for Hirschsprung’s disease, annular pancreas, diverticulitis is also seen in Down syndrome.
- Hearing defects
In about half of the cases, the conductive type of hearing loss is found. They are prone to otitis media during the first year of life.
- Eye problems
Increased risk for cataract, nystagmus, squint, and abnormalities of visual acuity, brush field spots (speckled appearance of the iris) can also be seen.
Certain types of cancer are more frequently found in Down syndrome. There is increasing risk (about 10 to 20 fold) for acute lymphoblastic leukaemia. Other cancers such as myeloid leukaemia and testicular cancers are common in Down syndrome.
- Endocrine abnormalities
Thyroid function tests are recommended in neonates as 13 to 54% of down patient has hypothyroidism. Thyroid function test should be repeated every year.
- Atlanto-occipital subluxation
In about 10 to 30% of cases subluxation of the Atlanto-occipital joint is found. This can cause spinal cord compression. Lateral neck radiography is recommended in Down’s patients of age between 3 to 5 years.
- Growth retardation
Reduced growth rate and prevalence of obesity are greater in Down syndrome. Weight is less than expected for length in downs, but increases disproportionately and becomes obese by 3 to 4 years.
Antenatal screening for Down syndrome
- First trimester (11 – 14 weeks of pregnancy)
Nuchal translucency, human chorionic gonadotropin (HCG) and pregnancy-associated plasma protein A. (PAPP-A)
- Second trimester (13 to 20 weeks of pregnancy)
Triplet test is done in the second trimester. It includes human chorionic gonadotropin (HCG), alpha-fetoprotein and unconjugated estradiol test.
Definitive investigation of down syndrome is karyotypic which shows trisomy 21 (47, XY + 21)
Treatment of Down syndrome
- Medical treatment
There is no medical treatment that can cure syndrome. The treatment protocol for down varies according to the conditions associated with Down syndrome. For example, if a person suffering from Down syndrome has a conductive hearing loss, they would benefit from hearing aids. Cases with seizure benefit of antiepileptic drugs. Hormone replacement therapy with thyroxine will benefit cases with hypothyroidism. All medications and measures are only for a symptomatic cure of the conditions associated with the Down syndrome and are not directed to the actual treatment of the down syndrome.
- Genetic counseling
Genetic counseling includes informing the parents about their disorder as soon as the diagnosis is confirmed. They should discuss the problems and disorders, informing the risks of recurrence while giving birth to another child and prenatal diagnosis.
Parents should be advised to learn about the Down syndrome. Learning Down syndrome helps with parenting the child. Parents should be encouraged to talk with other parents in similar situations. Advice should be given to parents to find a support system to help their child in educating. Parents should be gentle while correcting the mistakes they have committed while performing activities. Encourage a child to live an independent life, such as dressing and grooming themselves.
Parents are advised to look after what their child has learned in school and create an environment to implement them at home. They should be flexible on a day to day activities such as if a child fails to write by holding a pen they should teach their child with alternatives such as typing on the computer. They should be patient as well as hopeful about their child’s progress. Raising a down child can be difficult, but with patience, there are examples of children getting into mainstream education facilities.
Prevention of Down syndrome
Down syndrome cannot be prevented. Some risk factors can, however, be minimized such as bearing a child before the age of 35. Prenatal diagnosis may be helpful in knowing whether the child will suffer from Down syndrome or not. Folic acid supplementation may help in preventing down. This theory is still in research. Scientists believe Down syndrome is linked with the abnormal folate and methyl metabolism. So, folic acid supplementation may help in reducing risks. Preimplantation genetic diagnosis for couples at risk for bearing a child with Down’s syndrome may be beneficial in preventing the mother from giving birth to a child with Down syndrome.