INTRODUCTION

"Genetics is to biology what the atomic theory is to the physical sciences"

Human genetics is the science of biological variation in humans. Medical genetics is the science of human biologic variation, as it relates to health and disease.

The practice of medicine involves the three stages of diagnosis, prognosis and treatment. In medical genetics, diagnosis is important, in view of the variety of natural histories of the genetic disorders and their many patterns of inheritance. Prognosis forms the basis of genetic counseling. Treatment of genetic conditions however, is not that promising at present. With more refined techniques of intrauterine surgery, intrauterine drug therapy and gene therapy, the situation is bound to improve. Dysmorphology is the study of abnormalities of morphologic development.

CATEGORIES OF GENETIC DISEASES:

Genetic diseases fall into five main categories. They are :

• Single gene disorders
• Chromosome disorders
• Multifactorial disorders
• Somatic cell genetic disorders
• Mitochondrial genetic diseases

The last two are new categories which are becoming increasingly important in clinical medicine.

Single gene disorders

They are also called Mendelian or monofactorial disorders, and are traits produced by the effects of one gene or a pair of genes. The incidence in Western populations is 3.6 / 1000 livebirths.

1. Autosomal dominant traits are transmitted by autosomes, which are made up of 44 chromosomes, and excludes the XX pair in the female and XY pair in the male. These traits are expressed even when only a single copy of the dominant mutant gene is present. An example is Achondroplasia.
2. Autosomal recessive traits are transmitted as in the earlier category, on the nonsex chromosomes, but are only expressed when both copies of the gene are mutated. An example is Phenylketonuria.
3. X-linked traits are transmitted by genes carried on the X chromosome. An example is Duchenne muscular dystrophy.
4. Y-linked traits are transmitted on the Y chromosome and are therefore restricted to males and transmitted by males only. No disorders have as yet been located on the Y chromosome.

Chromosome disorders

These are conditions which arise from a change in the number or structure of any of the chromosomes. An example of the former is Down syndrome (extra chromosome No. 21) and an example of the latter is Cri du chat or cat cry syndrome. (deleted short arm of chromosome No. 5). General Incidence is 1.8 / 1000 livebirths.

Multifactorial disorders

In this category many genes and non-genetic environmental influences interact and contribute to the causation of the disorders. Examples include certain neural tube defects and atherosclerotic heart disease. Incidence 46.4 / 1000 livebirths.

Somatic cell genetic disorders

These arise after conception and are confined to certain somatic cells and their descendants. Most cancers, certain congenital malformations and autoimmune disorders belong to this category.

Mitochondrial genetic diseases

These are diseases resulting from mutations in chromosomes carried in mitochondria. An example is Leber's hereditary optic neuropathy.

The last two categories have a combined rate of incidence of 1.2 / 1000 livebirths, while other congenital anomalies account for a rate of incidence of 26 / 1000 livebirths. Congenital means anomalies seen at birth which may not be genetically caused, as seen in the Rubella syndrome. Similarly genetic does not necessarily mean congenital, as there are genetic conditions which manifest later in life, as for example adult polycystic kidney disease.

EFFECTS OF GENETIC DISEASE ON SOCIETY:

1. Infant mortality - leading cause.
2. Hospital admissions - 30% - 50% paediatric and 10% adult admissions.
3. Social burden - begin in childhood and continue throughout life.