In this article we will discuss about the syndromes of abnormalities that occurs in humans.
1. Autosomal Trisomy:
a. Down’s Syndrome (DS) or Trisomy-21:
Down’s syndrome is named after the physician J. Langdon Down who first described this genetic defect in 1866 and it was formerly called mongolism or Mongolian idiocy. It is usually associated with a trisomic condition for one of the smallest human autosomes (i.e., chromosome 21).
It is the most common chromosomal abnormality in live births (1/650 births). There are about 50 physical characteristics shown by DS infants soon after birth. These include mild or moderate mental retardation; eyes that slant up and out with internal epicanthal folds; a tongue that is large, swollen and protruding; small and underdeveloped ears; a single palmar crease; short stature; stubby fingers; an enlarged liver and spleen.
Women over 45 years of age are about twenty times more likely to give birth to a child with DS than women aged 20. Nondisjunction of chromosome pair 21 during oogenesis is the main cause of occurrence of trisomy-21.
This event is found to be affected either by senescence of oocytes, virus infection, radiation damage, etc. (e.g., mothers who have had infectious hepatitis prior to pregnancy may have three times more chances to give birth to DS infants). Nondisjunction of chromosome pair 21 during spermatogenesis can also produce children with DS, but paternal age does not seem to be associated with its incidence.
Lastly in about 2 to 5 per cent cases, the normal chromosome number is present (In – 40), but the extra chromosome 21 is attached (translocated) to one of the larger autosomes (usually chromosome 14).
b. Edward’s Syndrome or Trisomy-18:
First described in I960 by John H. Edwards and his colleagues, trisomy-18 is found to contain an incidence of about 0.3 per 1000 births. It is characterized by multiple malformations, primarily low-set ears; small receding lower jaw; flexed and clenched fingers; cardiac malformations; and various deformities of skull, face and feet. Harelip and cleft palate often occurs. Death takes place around 3 to 4 months of age.
Trisomy-18 children show evidence of severe mental retardation, which is more pronounced in females (the reason is still not clear). Like the Down’s syndrome, occurrence of Edward’s syndrome too is related with maternal age (i.e., 35 to 45- year-old mothers have more chances of giving birth to trisomy-18 infant).
c. Patau Syndrome or Trisomy-13:
This syndrome was described in 1960 by Klaus Patau and coworkers. Its incidence is about 0.2 per 1000 births. Individuals with Patau synckome appear to be markedly mentally retarded; have sloping forehead, harelip and cleft palate.
Polydactyly (of both hands and feet) is almost always present; the hands and feet are deformed. Cardiac and various internal defects (of kidney, colon, and small intestine) are common. Death usually occurs within hours or days, but the foetus may abort spontaneously.
2. Sex Chromosomal Trisomy:
a. Turner’s Syndrome (XO females):
A female with 44 autosomes and only with one X chromosome in her body cells exhibits symptoms of Turner’s syndrome. Such females are sterile and have short stature, webbed neck, a low hairline on the nape of the neck, broad shield-shaped chest, low intelligence, underdeveloped breasts, poorly developed ovaries, sparse pubic hairs and no axillary hair.
b. Poly-X females (XXX females):
Such females are called super-females because they possess an extra X chromosome (44 autosomes+3X chromosomes). Some females may have 4 or 5X chromosomes besides the normal autosomes. All such poly-X females are mentally retarded and sterile showing abnormal sexual development.
c. Klinefelter’s Syndrome (XXY males):
When an abnormal egg with XX chromosomes is fertilized by a sperm carrying Y chromosome, a zygote having three sex chromosomes (XXY chromosomes) is formed. The resulting young one is an abnormal sterile male showing the following features: small testicles, mental retardation, longer arms, feeble breasts (called gynaecomastia), high pitched voice and sparse body hairs.
d. XYY males:
Presence of an extra Y chromosome in males (XYY) results in their unusual height, mental retardation, severe facial acne during adolescence and criminal bent of mind. Their genitals are affected by developmental abnormalities.
3. Autosomal Deletions or Translocations:
a. Cri-du-chat syndrome:
Human babies missing a portion of the short arm of chromosome 5 (autosome) have a distinctive cat-like cry; hence, the French name “cri du chat” (cry of the cat) syndrome.
They are also mentally retarded (IQ below 20), have malformation in the larynx, moon faces, saddle noses, small mandibles (micrognathia), malformed low-set ears and microcephally (small head).
b. Philadelphia chromosome:
In humans, patients with chronic myelocytic (myologenous) leukemia (a kind of cancer) display an interesting chromosomal abnormality. In the bone marrow and in cells derived from it, is present a short chromosome, called the Philadelphia (Ph1) chromosome (so named because it was discovered in that city)?
Detailed cytological studies disclose Ph1 to be a number 22 chromosome that has lost most of the distal part of its longer arm. The deleted part of autosome 22 is translocated to one of the larger autosomes (most frequently to the distal end of chromosome 9). This translocation exhibits position effect and it is not transmitted to offspring of persons having Philadelphia chromosome (Ph1 does not appear in gametes of the patients).