INTEGRATION OF GENETIC COUNSELLING INTO MULTI-DISABILITY COMMUNITY BASED REHABILITATION PROGRAMMES

DISCUSSION LED BY :
Sridevi Hegde, Manipal Institute for Neurological Disorders(MIND), Manipal Hospital, Bangalore -560017 India.
Ph: 5266646

INTRODUCTION

Genetics is the science of heredity. It deals with the transfer of biological information from cell to cell, from parents to offspring and thus from generation to generation. Genetics has a major impact on all the areas of medicine. Genetic diseases make up a large proportion of the total disease burden in the population. Each human cell has approximately 50,000 to 100,000 different genes responsible for the human development and functions. Alterations in these genes or a combination of these can produce genetic disorders. Over 9,000 human genetic disease are known to date and the number increases day by day. In fact each one of us carry nearly 20 silent mutant genes.

The overall incidence of single gene disorders is 1 in 100 live births and that of chromosomal abnormalities is 1 in 150 at birth. Genetic counselling represents one of the central foci of medical genetics, which helps people to identify and understand what particular traits that may pass on to their children and also to determine particular risks that may influence pregnancy outcome. Genetic counselling is the process by which patients or relatives at risk of a disorder that may be hereditary, are advised of the consequences of the disorder, the probability of developing or transmitting it, and of the ways in which this may be prevented, avoided or ameliorated. Genetic counselling will help in making the best possible adjustment to the disorder in an affected family member.

Since there is no therapy or treatment for various genetic disorders (except for the biochemical/ inborn errors of metabolism) prevention of the occurrence of genetic disorder is the key to management. Prevention can be done through correct diagnosis/ identification of at risk family members, and prenatal diagnosis whenever possible, or by adopting other reproductive options.

WHAT ARE GENES AND CHROMOSOMES?

Every human being has over 100,000 genes that determine their hair and eye colour, type of build and other traits. The genes are like tiny switches that direct the growth and development of every part of our physical and biochemical systems. Genes are packaged into each of the 46 chromosomes inside most of our cells. Sperm and egg cells are different from other body cells. These reproductive cells each have only 23 unpaired chromosomes. When a single sperm and egg come together - when pregnancy begins - they form their own new cell with 46 chromosomes. The human being that results is genetically unique, with a blueprint half from each parent.

HOW INHERITANCE WORKS

Dominant Disorders
Each child gets half of its genes from each parent. Genes in each pair carry instructions for either dominant or recessive traits. If a parent passes on the gene for a dominant condition, there is a 50 percent chance that each child will have the same condition. Dominant disorders are quite variable, with symptoms ranging from none to severe. Birth defects caused by dominant inheritance include achondroplasia, a form of dwarfism, familial high cholesterol; Huntington disease, a progressive nervous system disorder; some forms of glaucoma that cause blindness if untreated; and polydactyly - extra fingers or toes. Marfan syndrome, which affects connective tissue, also is a dominant trait.

Recessive Disorders
If both parents are carriers of recessive genes, it can cause a birth defect - even if they are unaware of it. There is a one-in-four chance that each of their children will inherit the problem. If only one parent passes on the gene for the disorder, the normal gene received from the other parent will prevent inheritance of the condition. Recessively inherited diseases are often severe and may lead to early death. Examples are sickle-cell anaemia, a blood disorder, Tay-Sachs disease, which causes mental retardation and death, cystic fibrosis, a disorder of the lungs and digestive system, and phenylketonuria (PKU), a metabolic disorder.

X-Linked Inheritance
The X and Y chromosomes are the sex-determining chromosomes. Normal females usually have two Xs and males have one X and one Y. A disorder stemming from an abnormal gene on one of the X chromosomes is called an X-linked, or sex-linked disorder. An apparently normal mother with an abnormal gene on one X chromosome has a 50 percent chance of passing it to a male child, who inherits one X from her and a Y from his father. Carrier test are available for certain potentially damaging genetic traits. Some examples are blood test for disorders such as haemophilia, beta thalassemia (Cooley's anaemia) and sickle-cell disease. With rapid advances in genetics, more carrier screening tests for recessive genes are becoming available, such as for Duchenne muscular dystrophy and cystic fibrosis. Some examples of X-linked inheritance are haemophilia, in which the blood lacks a substance needed for clotting, red-green colour blindness and Duchenne muscular dystrophy, which causes muscle weakness.

Chromosome Disorders
Causes of genetic defects also include errors that occur when the egg or sperm are forming. Occasionally, an extra chromosome is produced, or a chromosome is missing or broken. This type of problem could come from either the mother or the father. The resulting "imbalanced" genetic material can give the baby too little or too much genetic information. When such an error happens, it is perpetuated each time the cells go through the division process. As the embryo grows, the scrambled genetic information may translate into abnormal body structures or functions, such as heart or kidney conditions, as well as mental retardation. Chances of having a child with a chromosomal error become greater as women grow older and their egg cells age. The possibility for a chromosomal error most commonly resulting in Down syndrome, increases throughout the childbearing years. Down syndrome is a pattern of mental retardation and physical abnormalities, often including heart defects.

Multi-factorial Inheritance
Sometimes, interaction of genes from one or both parents, plus interference from the environment may contribute to birth defects. These disorders and the way they are transmitted are less well understood. It is known, however, that the probability of their happening twice in a family is generally only 5 percent or less. Defects thought to result from multi-factorial inheritance include cleft lip and/or palate (malformations of the mouth); clubfoot (ankle or foot deformities); spina bifida or open spine (caused when the tube that forms the brain and spinal column does not close properly); Anencephaly, meningocele or meningomyolocele; water on the brain or hydrocephalus (which can cause brain damage); congenital heart defects; diabetes mellitus (abnormal sugar metabolism which usually appears later in life); and certain forms of cancer.

WHO IS ELIGIBLE TO RECEIVE COUNSELLING
The at risk population includes anyone who has a disability due to genetic disorder or has a family member with a genetic disability. These disabilities are different from those caused by environmental factors such as infection e.g. poliomyelitis, encephalitis, TORCH group of infections, or birth trauma. These non-genetic disabilities do not recur in the next offspring provided the environmental factors are taken care of.

The genetic factors responsible for genetic disorders with disabilities are

1. Chromosomal abnormalities e.g. Down Syndrome, trisomy of other chromosome or structural abnormalities of chromosome
2. Single gene disorders e.g. Biochemical disorders of Inborn errors of metabolism e.g. PKU, organic acidemias, galactosemias etc. or other genetic syndromes e.g. Cystic fibrosis, hemophilia, thalasenimia.
3. Multifactorial disorders which are due to a combination of multiple genes as well as environmental factors are many. Birth defects such as cleft lip and / or palate, neural tube defects, heart disease, diabetes and cancer belong to this category.

Other developmental and learning disability e.g. Autism, attention deficit disorder and emotional behaviour disorders also have a genetic component.

PREVENTION OF RECURRENCE IN MULTI-FACTORIAL DISORDERS

Periconception Vitamin therapy
Cleft lip and/or palate and neural tube defects are caused by a deficiency in folic acid and its receptors in the mother. The neural tube closes by 23rd day in embryo. Any defect in this closure gives rise to the neural tube defect. These defects can be prevented by periconceptional vitamin therapy. In Periconceptional vitamin therapy the prospective mother should take 4mg of folic acid 4 weeks prior to her conception and continue for 12 weeks after she conceives during the organogenesis period. This will prevent the recurrence of these defects in the offspring. Similarly this therapy also prevents recurrence of cleft lip and palate, so much so that in the US the flour and bread is fortified with 0.4 mg of folic acid. This prevents the occurrence these birth defects in the population and has reduced the incidence.

Early detection and treatment of inborn errors of metabolism of single gene disorders
New-born screening methods for inborn errors of metabolism can be incorporated in the rural and district community health care. A drop of blood that is collected from 3 or 4 day old babies onto a filter paper, can be mailed to the reference laboratories, and thus the metabolic disorders can be detected early. This is very important as early detection and dietary management will prevent the occurrence of the mental deficiency and other problems.

Counselling can be a helpful intervention for many life issues like adjustment or acceptance of given disability, management in terms of training, adaptive or vocational guidance and can help in finding employment and living independently. The most important aspect of training of these counsellors is to identify genetic disorders in a given population. This can be done by simply taking a detailed family history and recognising some of the genetic disorders. They can then advise the families about further tests to be done to screen them or organise courier services and liaison with reference labs/hospital to do these tests. The advice can then be given accordingly.

WHO NEEDS COUNSELLING

1. Couples who already have a child with mental retardation, an inherited disorder or a birth defect
2. Couples whose infant has a genetic disease diagnosed by routine new-born screening
3. Women who have had two or more miscarriages, or babies who died in infancy
4. Women who are pregnant or planning a pregnancy after the age of 34 years
5. Couples who are first cousins or close blood relatives
6. Couples who would like more information or testing about genetic defects that occur frequently in their communities or ethnic group

HOW GENETIC COUNSELLORS CAN HELP
If the couple have a child with a genetic disorder the counsellor can be of great help by providing a complete and accurate view of the situation, the nature of the birth defect and what its recurrence would mean in practical terms for all involved. The counsellor can also provide emotional support and understanding during what can be a very difficult time. If there are decisions to be made about the pregnancy, care of a child, having more children, or about the ability of the family to cope with ongoing problems, the parents can make informed choices with the facts in hand. The concept of genetic defects can be frightening and confusing. A genetic counsellor is trained to help translate the information clearly and to be an emotional resource to help affected individuals deal with the situations they face.