NUMERICAL CHROMOSOMAL DISORDERS

Dr Idara

Numerical Chromosome disorders

Numerical chromosomal abnormalities result from Nondisjunction usually. This is an error in cell division in which there is a failure of a chromosomal pair or two chromatids of a chromosome to disjoin during mitosis or meiosis. As a result, the chromosomal pair or chromatids pass to one daughter cell and the other daughter cell receives neither.

Nondisjunction may occur during maternal or paternal gamatetogenesis.

Aneuploidy and Polyploidy

Aneuploidy is any deviation from the human diploid number of 46 chromosomes.

An aneuploid is an individual that has a chromosome number that is not an exact multiple of the haploid number of 23. ( e.g. 45 or 47).

A polyploid is an individual that has a chromosome number that is a multiple of the haploid number of 23 other than the diploid number ( e.g. 69).

The principal cause of aneuploidy is nondisjunction during cell division resulting in unequal distribution of one pair of homologous chromosomes to the daughter cells.

One cell ends up with two chromosomes and the other has neither chromosome of the pair.

As a result, the embryo’s cells may be hypodiploid ( 45x, in Turners) or hyperdiploid( 47, as in Trisomy 21)

If three chromosomes are present instead of the usual pair, the abnormality is a Trisomy.

Trisomies are the most common abnormalities of chromosome number.

Causes of Trisomies

The most common cause of a Trisomy is meiotic nondisjunction resulting in a gamate with 24 instead of 23 chromosomes and subsequently in a zygote with 47 chromosomes.

Embryos with monosomy – missing a chromosome – usually die.

About 99% of embryos lacking a chromosome (45,x) spontaneously abort.

Types of trisomies

Trisomies could result to autosomes or sex chromosomes.

Trisomy of the autosomes is associated with three main syndromes:

A. Trisomy 21 or Down SyndromeB. Trisomy 18 or Edwards SyndromeC. Trisomy 13 or patau Syndrome

Down Syndrome

Down syndrome is a chromosomal condition that is associated with intellectual disability, a characteristic facial appearance- Epicanthal folds; flattened nasal bridge; brachycephaly; upward slant to palpebral fissures; protruding tongue.

They also have a single simian crease; clinodactyly of the 5th digit; congenital heart defects and poor muscle tone (hypotonia) in infancy.

A person with Down Syndrome has an extra chromosome #21. Instead of a pair, this person has 3 chromosomes - a condition called TRISOMY (tri = three)

Individuals with Down syndrome also have an increased risk of hearing and vision problems.

Additionally, about 1 percent of children with Down syndrome develop cancer of blood-forming cells (leukemia).

Adults with Down syndrome have an increased risk of developing Alzheimer disease. Although Alzheimer disease is usually a disorder that occurs in older adults, about half of adults with Down syndrome develop this condition by age 50.

Trisomy 18 ( Edward’s Syndrome)

People with Trisomy 18 have mental retardation, growth retardation,; prominent occiput; short sternum, ventricular septal defect; micrognathia( small jaw); low -set malformed ears, clenched fists with the second and fifth digits overlapping the third and fourth,

Rocker- bottom feet ( posterior prominence of the heels).

Trisomy 13 ( Patau syndrome)

Infants have mental deficiency, severe central nervous system malformations, sloping forehead; low -set malformed ears, scalp defects; micropthalmia ( abnormally small eyes); bilateral cleft lip and/ or palate; polydactyly, rocker- bottom feet.

Trisomies of the sex chromosome

Trisomy of the sex chromosome is a common condition; however, because there are no characteristic physical findings in infants or children, this disorder is not usually detected until puberty.

Chromosome complement

sex Incidence Characteristics

47xxx female 1:960 Normal appearance; usually fertile 15- 20 % are mildly mentally retarded

47xyy male 1: 1080 Normal appearance; usually tall; often exhibit aggressive behavior

Klinefelter’s syndrome

Klinefelter syndrome results from the presence of a single extra copy of the X chromosome in each of a male's cells (47,XXY).

Extra copies of genes on the X chromosome interferes with male sexual development, preventing the testes from functioning normally and reducing the levels of testosterone.

Affects 1 in 500 to 1,000 males. Most males with Klinefelter’s syndrome have one

extra copy of the X chromosome in each cell.

Signs and symptoms

Patients with Klinefelter syndrome have small testes, hyalinization of seminiferous tubules; aspermatogenesis; often tall with disproportionately long lower limbs.

Intelligence is less than in normal siblings. About 40% of these males have gynaecomastia.

Only one disorder present. Viz:• Turner Syndrome 45 x

Monosomy of the sex chromosome

Turner syndrome(45XO)

Turner syndrome is a chromosomal condition that affects development in females.

It results from monosomy of the X Chromosome The most common feature of Turner syndrome

is short stature, which becomes evident by about age 5.

An early loss of ovarian function (streak ovaries) is also very common.

A small percentage of females with Turner syndrome retain normal ovarian function through young adulthood.

Turner Syndrome

About 30 percent of people with Turner syndrome have Webbed neck, a low hairline at the back of the neck, puffiness or swelling (lymphedema) of the hands and feet, skeletal abnormalities, and/or kidney problems.

One third to one half of people with Turner syndrome are born with a heart defect.

Most girls and women with Turner syndrome have normal intelligence. Developmental delays, learning disabilities, and behavioral problems are possible, although these characteristics vary among affected individuals.

occurs in about 1 in 740 newborns