Question

DOWN SYNDROME

What is the history of the disease?

How common is it, and how is it diagnosed?

What are the major signs, symptoms?

What techniques sre used for genetic screening of the disease?

Answer 1

- Down syndrome is a chromosomal disorder in which there is an extra chromosome 21 (47, XY +21 or 47, XX +21). It is also known as trisomy 21 or mongolism. A child with Down syndrome has severe physical and mental growth retardation.

- Down syndrome is named after a British physician Dr John Langdon Down who discovered this disorder and described its features.

- Overall it affects 1 in 1000 live births annually. The incidence is more with increased maternal age (commonly above 35 years of age); incidence at 35 years of maternal age = 1:270; at 40 years = 1:100; at 45 years = 1:50.

- It is diagnosed prenatally by chorionic villous sampling or by amniocentesis. Chorionic villous sampling is done around 11-13 weeks of gestation in which transcervical or transabdominal aspiration of chorionic villous tissue (a placental tissue) is done under ultrasound guidance and the cells are examined using polymerase chain reaction (PCR) technique for genetic and chromosomal abnormalities including Down syndrome. Amniocentesis is done between 16-18 weeks of gestation where amniotic cells are extracted from amniotic sac of the fetus by transabdominal or transcervical aspiration using needle under ultrasound guidance and the cells are examined for chromosomal abnormalities. Postnatally, Down syndrome is mainly diagnosed by clinical examination.

- Symptoms and signs of Down syndrome:- intellectual disability (most common genetic cause of intellectual disability is Down syndrome), short stature, short neck, excess nuchal (neck) skin, hypotonia (flopiness), upward slanting eyes, epicanthic folds, single palmar crease (simian crease), sandal toes (increased gap between first and second toe), low set ears, enlarged tongue (macroglossia). Down syndrome is also associated with congenital heart disease like atrial septal defect. Other congenital anomalies associated with Down syndrome are hypothyroidism, tracheo-esophageal fistula, duodenal atresia.

- Down syndrome is screened prenatally in the first trimester (between 11-13 weeks of pregnancy) by increased beta hCG (human chorionic gonadotropin) + increased pregnancy associated placental protein A (PAPP-A) + nuchal translucency (on ultrasound examination) called as "combined test".

- In the second trimester (between 16-18 weeks), Down syndrome is screened by triple test and quadruple test (quad test). In triple test if there is decreased maternal serum alpha fetoprotein + decreased unconjugated estradiol + increased beta hCH (human chorionic gonadotropin), the chances of the fetus having Down syndrome is high. Quad test consists of triple test + maternal serum dimeric inhibin A. Diagnosis can be confirmed only by chorionic villous sampling or amniocentesis.

- Harmony prenatal test is a non-invasive parental test to detect trisomy 21 (Down syndrome). It detects the amount of fetal cell-free DNA in the maternal blood. If there is Down syndrome there will be excess of particular chromosomes cell free DNA that will be detected by this test.