Down Syndrome: Risk factors, cause, symptoms, diagnosis and treatment.

Down syndrome is the most common chromosomal abnormality in humans and the most common cause of intellectual disability. Normally a baby is born with 46 chromosomes. When Down syndrome occurs, a baby is born with an extra chromosome. A medical term for having an extra chromosome is “trisomy”. Down syndrome is also called “trisomy 21” since it occurs at the chromosome 21. This extra copy of chromosome has a negative impact on a newborn’s mental and physical growth. Along with mental and physical growth retardation, down syndrome patients can also present other diseases such as congenital heart diseases, Alzheimer's disease, and leukemia (one kind of blood cancer). Since this condition is life long, supportive care should be given to the patient. According to World Health Organization (WHO), the estimated incidence of down syndrome is 1 in 1000 births worldwide and 1 in 700 birth in USA. (CDC). Each year approximately 3000 to 5000 children are born with this chromosomal disorder.

Risk factors:

1.      Older mothers (age 35+): Because the chances of having a baby with down syndrome increases with the age of the mother, it is recommended that women over the age of 35 have pre-birth testing for this condition.

2.         Folate metabolism

3.         Dietary

4.         Life style

5.         Environmental

6.         Occupational

7.         Genetic and epigenetic

Types and causes:

1.         Trisomy 21 down syndrome: 95% of the case is due to meiotic nondisjunction. With this type of down syndrome, each cell in the body has 3 separate copies of chromosome 21 instead of the usual 2 copies.

2.         Translocation down syndrome: 4% of the case is due to unbalanced Robertsonian translocation. It is most typically between chromosome 14 and 21. This occurs when an extra part or a whole extra chromosome 21 is present but it is attached or trans located to a different chromosome rather than being a separate chromosome 21.

3.         Mosaic type down syndrome: Only 1% of the cases are due to post-fertilization mitotic error. Baby has 3 copies of chromosome but other cells have the typical 2 copies of chromosome 21.

4.         Cytogenic and molecular studies suggests that dup21(q22.1-22.2) is sufficient to cause down syndrome.

Signs and symptoms:

1.         Flattened face, specially the bridge of the nose.

2.         Prominent epicanthal folds (almond shape eyes)

3.         Single palmar crease

4.         Gastrointestinal abnormalities (duodenal atresia)

5.         Congenital hearth abnormalities (septal defect)

6.         Brush field spots (gray brown spot in the iris)

7.         Short neck

8.         Small ears

9.         Tongue that tends to stick out from the mouth

10.   Short in height

11.   Gap between 1^st and 2^nd toes

Diagnosis:

Screening test: Test for alpha fetoprotein (AFP), nuchal translucency (NT), amniocentesis, chorionic villus sampling (CVS) and ultrasound (1^st trimester).

1^st trimester: increased in B-hcG and decrease in PAPP-A

2^nd trimester: decrease in AFP + Estriol and increase in B-hcG and inhibin A.

Complication:

1.         Cardiac: Atrioventricular septal defect (AVSD)

2.         Respiratory: Obstructive sleep apnea, lung infection, aspiration and cor-pulmonale.

3.         GIT: GERD, chocking and gagging on feeding and obesity.

4.         Ophthalmic: Myopia, hyperopia and astigmatism.

5.         Otolaryngologic: Hearing loss, ear infection and ear effusion.

6.         Endocrine: Hyper and hypo thyroidism, diabetes mellitus type 1.

7.         Hematologic: AML and ALL

8.         Immunologic: Recurrent respiratory and systemic infection.

9.         Orthopedic: Scoliosis, him instability, patellar instability and foot problems.

10.   Psychiatric and behavioral: Depression, anxiety, OCD and schizophrenia.

11.   Alzheimer's disease: Early onset of Alzheimer's disease.

Prevention:

There is no way to prevent down syndrome however genetic counseling before becoming pregnant is recommended for mothers age of 35+. Knowing beforehand that a baby will be born with down syndrome can help provide special support throughout life.

Treatment:

Down syndrome is a lifelong condition. There is no cure for this disorder but providing appropriate support and care that can improve a patient’s mental and physical abilities. Down syndrome patients need special services which includes, speech, occupational and physical therapy. Children with this condition may need extra help or attention at school as well. 

By-

Maruful Bhuiyan

MD candidate, Chicago. IL, USA.

Editor-

Fariha Ahmed

Student at City University of New York

New York, USA.

(Any suggestion, comment and correction will be highly appreciated)

Reference: 
1. CDC-Facts about Down Syndrome
2. WHO-Genes and chromosomal diseases
3. PubMed-Risk factors for Down syndrome
4. Medscape -Down Syndrome