Down syndrome

Overview of Down syndrome

The rate of growth of genetic diseases has been very alarming in the recent years. The factsheets of Global Genes show that nearly 300 million people worldwide suffer from one of the 7000 rare genetic diseases that have been identified till date. The records documented by Global Genes also show that around 6% of the newborns are born with these diseases which start manifesting themselves severely within a year of birth. One of the commonly studied diseases of this category is Down syndrome. It has a number of conspicuous physical manifestations. The 2014 statistics provided by the Center for Disease Control and Prevention (CDC) show that each year, nearly 6000 babies are born with Down syndrome worldwide. They have also shown that between the years 1979 and 2003, there has been a 30% increase in the number of children born with Down syndrome. The World Health Organisation (WHO) has proved through an epidemiological survey that nearly 60-80% of the children having Down syndrome have auditory defects.

What is Down syndrome?

Down syndrome is a form of rare genetic disorder which is caused by the presence of all or a segment of a third copy of the 21^st chromosome. This condition was first described in the year 1866 by John Langdon Down, an English doctor. This is basically a congenital disorder that affects 1 in every 700 children worldwide. The disease may affect males and females equally. It has been observed that the parents of these children are absolutely normal. The extra chromosome occurs accidentally and by chance. The probability of occurrence of the disease increases from 0.1% or less in mothers below 20 years of age to 3% in mothers close to 45 years of age. The children having this disease exhibit certain major physical and intellectual disabilities. By and large, Down syndrome is the most widely studied category of chromosomal abnormality in humans.

What are the causes of Down syndrome?

As discussed in the previous section, Down syndrome is a rare genetic disorder that occurs due to the occurrence of a third copy of chromosome 21. Hence the disease is also called Trisomy 21. Down syndrome occurs due to an accidental error in cell division, which is known as nondisjunction. Two other forms of chromosomal anomalies namely translocation and mosaicism can also contribute to Down syndrome. Irrespective of the root of origin, all people suffering from this disease have an extra genetic material (due to overexpression of a segment of the 310 genes located on chromosome 21) that alters the course of development and gives rise to aberrant syndromes.

What are the major symptoms of Down syndrome?

The symptoms of Down syndrome can be classified into several categories. These are listed below-

Physical symptoms: 

• Poor muscle tone (hypotonia)
• A very small nose (due to a suppressed nasal bridge)
• Abnormally shaped ears (dysplastic ears)
• A deep crease at the center of the palm
• Hyperflexibility of joints
• Abnormal curvature of the fifth finger (due to malformation of the middle phalanx bone)
• Presence of tiny folds on the inner corner of the eyes (epicanthal folds)
• Presence of excessive space between the first and the second toe
• Abnormally large tongue
• Upward slant of the eyes (due to oblique palpebral fissures)

Neurological symptoms: 

• Intellectual disability
• Low IQ (10-35)
• Occurrence of infantile spasms and epileptic seizures
• Delayed and indistinct speech
• Depression and anxiety
• Memory problems

Sense organs: 

• Inability of the two eyes to move together (strabismus)
• Cone-shaped cornea (Keratoconus)
• Refractive errors
• Ear infections
• Hearing loss (sensorineural type)

Cardiovascular symptoms: 

• Atrioventricular septal defect
• Thickening of the arteries
• Mitral valve abnormalities

Endocrinal symptoms: 

• Hypothyroidism
• Grave’s disease
• Diabetes mellitus

Gastrointestinal symptoms: 

• Duodenal atresia
• Imperforate anus
• Celiac disease
• Gastroesophageal reflux disease

Dental symptoms: 

• Periodontal disease
• Ulcerative gingivitis
• Cleft lip
• Enamel hypocalcification

Types of Down syndrome

According to the origin of the disease and its intensity, Down syndrome can be classified into the following three classes.

• Trisomy 21: It occurs in 95% of the cases. It takes place when one of the parents through the process of non-disjunction lends two copies of chromosome 21 to the egg or the sperm instead of one. Hence the child has an extra chromosome 21 in all the cells. This anomaly also occurs due to the failure of the 21^st chromosome to separate during the egg or sperm development.
• Translocation: In this case, a portion of the chromosome 21 breaks off during cell division and attaches to another chromosome. In these patients, one chromosome is larger, due to the presence of the extra segment. But the number of chromosomes is 46, not 47.
• Mosaicism: In Mosaicism, nondisjunction of chromosome 21 occurs in one of the early cell divisions that occur immediately after fertilization. In this disease, a mixture of two types of cells occurs, some of which contain 46 chromosomes and some contain 47.

Diagnosis

The following diagnostic tests are carried out, mainly in the pre-natal stage, for the detection of Down syndrome-

• Quad screen (measures maternal serum alpha-fetoprotein)
• Cell-free fetal DNA (via venipuncture)
• Integrated test
• Amniocentesis
• Chorionic villus sampling

Treatment and Prevention

The treatment mainly aims to improve quality of life of the affected individual. Parents should be educated about the developmental delays experienced by the affected children. The developmental milestones are delayed and the child takes more time to sit, crawl, walk, and to start speaking. A team of speech therapists, occupational therapists, and physical therapists can work together to improve the motor, language, and social skills of the child. This will help the child to lead a normal life as much as possible.

The child may require the help of a primary care pediatrician, pediatric cardiologist, pediatric endocrinologist, pediatric neurologist, developmental pediatrician, audiologist etc. at various stages of life.

Underlying medical condition (such as conditions associated with the heart and the gastrointestinal system) are evaluated and treated. In some cases, surgeries are required to treat the disorders. The amount of care and support required depends on the physical function and the intellectual ability of the child. Different stages of development might require different approaches for treatment. However, early intervention can significantly improve the quality of life of the child.

Prevention of the condition is not feasible. However, risk factors (such as mother’s age at the time of pregnancy) can be taken care of.

References