The Secrets of Life (2) - Chromosomes and Health and Development

Normally every cell of the human body has 46 chromosomes, organized in 23 pairs (22 pairs of autosomes - same for female and male, and one pair of sex chromosomes - XX in female and XY in male). Hence, the chromosomes of an ordinary female is described as 46,XX and a male as 46,XY. During the formation of the egg and the sperm, the chromosome pairs separate so that each egg or sperm cell contains only one copy of the 23 pairs of chromosomes. When the egg and the sperm combine together at the time of conception, they form the first cell of the child which now has 46 chromosomes as the parents. However, during these processes of separation and combination, error may occur resulting in changes in the number, size and structure of the chromosomes. This will then change the amount or the arrangement of genetic information in the cells which may result in problems in health and development of the child:
A. Change in number of chromosomes
Sometimes, mistake may happen in the separation of the chromosome pairs during the formation of the egg or sperm, resulting in either an addition or deletion of chromosomes. When a sperm or egg with the usual 23 chromosomes combine with this egg or sperm with a changed number of chromosomes, it will result in an embryo with chromosomes of number more than or less than the usual number of 46.
Addition and deletion of chromosome have strict rules:
. deletion of any autosome (chromosome 1 - 22) is usually incompatible with life, resulting in miscarriage (流產) or stillborn (胎死腹中) in the first 3 months of pregnancy.
. addition of 2 or more autosomes is also usually incompatible with life in the first 3 months of pregnancy.
. addition of autosome other than chromosome 21 usually results in non-survival in infancy or early childhood (usually within the first year).
. addition or deletion of sex chromosomes (X or Y) is possible except that in the resultant chromosome, there cannot be Y-only chromosomes (i.e. Y chromosome must have an X chromosome in order for survival).
As such, the possible common changes in number of chromosomes and their related effect on the health and development of the child are listed as follows:

Chromosome condition	Description	Syndrome	Symptoms
47,XX+21 47,XY+21	47 chromosomes with extra chromosome 21 in female or male	Down’s syndrome (唐氏綜合症)	Mental retardation, smaller growth parameters including height, neck, head circumference etc., flat face. Usually infertility in male. High risk of miscarriage in female with 50% chance of conceiving babies with Down’s syndrome.
45,X	45 chromosomes with single X chromosome in female	Turner syndrome	Normal intellectual performance, slower growth and lower height, infertility
47,XXY	47 chromosomes with extra X chromosome in male	Klinefelter syndrome	Learning difficulty, tendency to grow at quicker rate, small testcles/penis, infertility
48,XXXY 49,XXXXY	rare extensions with additional X chromosomes) of 47,XXY (male)		More exaggerated features of 47,XXY syndrome
47,XXX	47 chromosomes with extra X chromosome in female	XXX syndrome	‘super-female’, usually no observable physical and medical anomalies apart from being taller than average, normal sexual development, risk of learning difficulty
48,XXXX 49,XXXXX	rare extensions with additional X chromosomes) of 47,XXX (female)		Decreased mental and physical ability, tall texture
47,XYY	47 chromosomes with extra Y chromosome in male	XYY syndrome	‘super-male’, usually no observable physical and medical anomalies apart from being taller than average, normal sexual development., risk of learning difficulty

B. Change in size of chromosomes
Sometimes, a portion of the chromosome is duplicated or deleted during the formation of the egg or sperm, resulting in extra or loss of genetic material in the chromosome. Some common examples and their related effect on the health and development of the child are listed as follows:

Chromosome condition	Description	Syndrome	Symptoms
46,XX,dup(17) (p12)	Duplication of p arm, band 1 and sub band 2 of chromosome 17 in female	Charcot-Marie-Tooth disease (腓骨萎縮症)	Loss of muscle tissues in feet and legs, high arch, claw toes.
46,XX,5p-	Deletion of part of p arm of chromosome 5 in female	Cri-du-chat syndrome (貓哭症)	Intellectual disability, delayed development, small head size, high-pitched cry sound like cat.

C. Change in structure of chromosomes
C.1 Inversion
Sometimes a segment of the chromosome breaks off, rotates 180 degrees and reconnects to the original chromosome during the formation of the egg or sperm. (e.g. 46,XY,inv(12) (p11.2q24.3) refers to a male with inversion in chromosome 12 from p arm band 1, sub-band 1, sub-sub-band 2 to q arm band 2, sub-band 4, sub-sub-band 3.)

Inversion usually does not cause any problems in health and development of the child as there is no gain or loss of genetic material. Only the order of the genetic information is changed. However, there may be complications and problems when the child further has children. We shall leave the discussion of these in a later blog.
C.2 Translocation
Sometimes, segments of 2 chromosomes break off and exchanged during the formation of the egg or sperm. (e.g. 46,XX, t(4,20) (q31,q12) refers to a female with translocation between chromosome 4, long (q) arm band 3, sub-band1 and chromosome 20, long (q) arm band 1, sub-band 2.)

Translocation is much more complicated than inversion as there is an exchange of chromosome segments (i.e. genetic material) between different chromosomes. It may or may not cause problems to the health and development of the child as depending on type of chromosomes involved (e.g. exchange of genetic material between autosome and sex chromosome) and the portion of chromosomes involved.

The above gives some simplistic views on how changes in chromosomes may affect the health and development of the child. It is recommended that affected individuals should seek professional advice from genetic counseling on details of medical issues, and implications on any possible inheritance issues when considering births of offspring ...................