Everything You Need to Know About Down Syndrome: Overview, Signs and Symptoms, Causes, Diagnosis, and Treatment

When people talk about chromosomal disorders, Down syndrome is one of the most common examples they refer to. It is actually the best known and most widely studied chromosomal ailment. It is also the top cause of cognitive problems and intellectual disability. Additionally, it is associated with a series of systemic issues and complications outside of the nervous system.

Overview

Every cell in the body has DNA stored in its nucleus (not red blood cells, though, because they do not have a nucleus). Genes are grouped in chromosomes every time the cell divides. Our cells have 23 pairs of chromosomes (46 chromosomes total), and every parent provides half of that genetic material. In Down syndrome, patients do not have only 46 chromosomes. They have 47 because chromosome 21 has an extra unit.

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Each chromosome has thousands of genes, and each one encodes a new protein. Having one extra chromosome means having thousands of additional substances. In most cases, fetuses cannot survive this surplus, but Down syndrome is different. The disease is not fatal, but it is associated with several body and brain development changes.

Signs and symptoms

Patients with Down syndrome are relatively easy to diagnose. They have a set of signs and symptoms that stand out, even in people who do not have any medical knowledge.

1.Physical variants in the skull and face

In the skull and face, patients with Down syndrome have particular variants. They have a flattened face with a smaller head than the average, and a small nose and mouth. The tongue is protruding, and they have small ears and excess skin in the back of the head.

2.Physical variants in the extremities and other body parts

The rest of the body also has different changes. For example, patients with Down syndrome have shortened extremities with broad and short hands. You can examine their fingers and realize that the fifth finger is smaller because the middle phalanx is shorter than usual. Similarly, you will also find a longer space than usual between the first toe and the second.

3.Central nervous system issues

Intellectual disability in patients with Down syndrome is moderate or severe. The IQ ranges between 2 and 85, with a mean IQ of 50. Beyond their cognitive abilities, their bodies are also affected by nervous system alterations. Their muscles are hypotonic; they do not have proper muscle tone because the nervous system is not functioning correctly. They often have sleep apnea and sometimes insomnia and other sleeping problems. Up to 10% of these patients have recurrent seizures or at least spasmodic movements.

4.Psychiatric and behavioral issues

Patients with Down syndrome are genuine, very gentle, spontaneous, and charming. Unlike general thought, they are not like autistic children who are not social. They can understand social cues and can be very patient and tolerant. In some cases, they can also display some anxiety symptoms, but this is not the typical Down syndrome presentation. Up to 38% of them have overlapping psychiatric problems, especially attention deficit and hyperactivity disorder, disruptive or defiant behavioral disorders, and stereotypical movements with or without autism. In adults, an obsessive-compulsive disorder also becomes somewhat common.

5.Cardiovascular issues

Children with Down’s syndrome sometimes have severe cardiovascular problems. Heart defects are widespread, and up to 50% of patients have one or more. Patients hospitalized are more likely to have cardiovascular issues, and they are sometimes very severe and lead to the patient’s death before age 2 years old. 30% of patients have two or more cardiac defects, and heart murmurs are common in this group.

6.Skin disorders

80% of children with Down’s syndrome have at least one type of skin disorder. They could be dark body marks (localized hyperkeratotic lesions), dry skin (xerosis), folliculitis when they reach adolescence, recurrent infections, and sometimes alopecia. In some cases, their skin disorders are associated with other problems, mostly hormonal and autoimmune issues. That’s why patients may also develop vitiligo and other immune-related skin disorders.

7.Gastrointestinal problems

Early in their development, Down syndrome babies usually have problems in the process of starting to feed on their mom’s breast. When they begin feeding appropriately, more than 10% of these patients start vomiting and have other gastrointestinal signs due to abnormalities such as duodenal stenosis or atresia. Fistula formation, an imperforate anus, and Hirschsprung disease may also be observed in this group of patients. More recently, studies have shown that Down syndrome patients have an increased risk of celiac disease. Some of them are intolerant to gluten and start displaying loose stools, abdominal pain, and growth failure when this condition is not detected on time. Due to the shape of the mouth and upper gastrointestinal tract, they may also have swallowing problems and suffer from gastroesophageal reflux.

8.Skeletal abnormalities

Right from the start, Down syndrome babies are born with low birth weight and length. Their head circumference is also smaller as compared to other babies. They continue to be shorter and tend to have a lower weight as compared to control patients of the same age. However, it is essential to note that 50% of adults with Down syndrome are obese. Accordingly, there is currently a special growth chart for Down syndrome patients because they cannot reach the same size and weight as control patients.
One reason for this growth retardation is an IGF-1 deficiency, but the exact mechanism is unknown. On the other hand, Down syndrome patients have particular skeletal abnormalities. For example, short feet, hands, and digits. Their fifth finger is shorter and curved. The pelvis bone looks different in X rays, and their joints are very mobile (joint laxity).

9.Endocrine abnormalities

One of the most common endocrine problems is hypothyroidism. 50% of Down syndrome adults have hypothyroidism, and they develop this condition as they grow up, usually through conditions such as Hashimoto thyroiditis. In only a few cases, Hashimoto thyroiditis causes hyperthyroidism instead of hypothyroidism. Another common endocrine disorder is type 1 diabetes, which is found at a higher rate than the rest of the population. 50% of females and most males are infertile.

10.Immune problems

Patients with Down syndrome often have abnormalities with their white blood cells. They have a high risk of leukemia, especially during their initial 5 years of life (56 times higher than regular patients). This causes immune problems, blood clotting problems, and many other symptoms found in leukemia patients. But even if they do not develop leukemia, Down syndrome patients are more susceptible to infectious diseases (12 times more susceptible according to studies). The most common infectious disease is pneumonia.

Causes

As noted above, Down syndrome patients are born with an extra copy of chromosome 21. Instead of having two chromosomes, they have 3 full copies or at least a big chromosomal translocation in pair 21, resulting in three copies. Almost 95% of patients have a complete copy. Another possibility is mosaicism (in around 3% of patients).

How are they born with an extra copy of chromosome 21? Because there’s a failure in the disjunction of the chromosome during meiosis of one of the gametes. In other words, either the mom’s egg or dad’s sperm has two copies of chromosome 21 instead of one. This is because the extra copy couldn’t separate properly during cell division. In most cases (95% of the time), the maternal egg is the one with the extra copy. This is more common in aging women who conceive, which is why late pregnancy has a very high risk of Down syndrome.

Diagnosis

The diagnosis of Down syndrome usually considers the characteristics listed in the signs and symptoms section. This syndrome is usually detected early in the course of pregnancy in women who screen correctly, especially in high-risk pregnancies.

When they are taken to the doctor, he would be interested to know a few facts to guide the diagnosis:

In most cases, the parents come to the doctor’s office with concerns about developmental delay, visual or hearing problems, and recurrent respiratory infections
Doctors will ask if the patient is vomiting or feeding adequately because some of them develop a blockage in the gastrointestinal tract
The delay in cognitive abilities is fundamental for the diagnosis
Doctors will also highlight the importance of cardiovascular health, especially palpitations, fainting, arrhythmia, etc.
Sleeping problems, sleep apnea, daytime drowsiness, and difficulty waking are also crucial for the diagnosis of this condition.
In some cases, Down syndrome patients can be subject to sexual abuse, and doctors may need to perform a complete physical exam to rule this out.

In most cases, the diagnosis is not a problem, and it is not always necessary to perform a DNA test. However, doctors may need to know about the type of trisomy (full trisomy, translocation, or mosaicism), which is why they usually order a DNA test. In some cases, it will be recommended to differentiate Down syndrome with a trisomy 18, which has similar features. In that scenario, it is also recommended a DNA test.

Treatment

Treatment of Down syndrome should evaluate the potential of the patient to give direction in the intervention. Schooling and community placing are to be chosen accordingly.

There is currently no successful treatment to prevent intellectual disability in Down syndrome. However, it is still possible to improve their quality of life through medical care and interventions.

Immunizations are recommended precisely the same as in other children. They are even more important in Down syndrome due to their increased sensitivity to infectious diseases. Surgery is sometimes needed, and most of them aim at correcting cardiovascular problems. And even after the patient is found physically healthy and well, regular monitoring and screening are required to prevent new health conditions. In older adults, screening is also essential for early diagnosis of dementia, hypothyroidism, epilepsy, and other problems.

Surgery: Surgical care is usually done in early childhood or the newborn after detecting cardiac abnormalities. This type of treatment is required to prevent complications and increase the chance of survival. Besides cardiac abnormalities, gastrointestinal atresia, fistula, imperforate anus, pyloric stenosis, and other structural problems can also be corrected by surgical interventions. Other causes of surgery include congenital cataracts and atlantoaxial subluxation.
Dietary recommendations: The diet only changes in patients with celiac disease. They should have a gluten-free diet and fix their calorie intake to maintain a healthy weight.
Thyroid hormone: It is essential to detect hypothyroidism early and start treatment with thyroid hormone. Otherwise, thyroid hormone deficiency can speed up intellectual deterioration and worsen the quality of life.
Support therapy: Patients with Down syndrome can have several health problems throughout their lifetime. It is important to detect and treat emergent cardiac problems, probably with diuretics and digitalis, spasms and seizures with anticonvulsants or steroids, and restorative dental therapy in case of periodontal disease.
Psychotherapy: Behavioral therapy is important in Down syndrome, especially when there’s a psychiatric disorder. Psychologic support, group therapy, and other modalities may be used. In some cases, patients may need pharmacologic treatments.

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During adolescence, patients with Down syndrome require an annual audiological evaluation and an ophthalmologic evaluation every three years. They should be monitored regularly to detect and treat conditions as soon as possible. For instance:

Dermatologic issues such as fungal infections and folliculitis should be treated accordingly
When patients are starting to gain excess weight, and in cases of obesity, a caloric intake reduction should be recommended, as well as increasing physical activity levels.
Antibiotics, not only to treat infections but also as prophylaxis. For example, in dental procedures for patients with mitral valve prolapse.
Detecting and treating sleep apnea.
Language and speech therapy are often fundamental, especially in intelligible patients at a young age or those without an expressive language in adolescence.