INHERITANCE OF GENETIC DISEASES DUE TO CHROMOSOMAL ABERRATIONS
Heredity plays a part in almost all diseases. Recent advances in gene research have allowed a steadily increasing number of specific genes and genetic factors to be linked to a wide variety of medical complaints. There are currently approximately 6,000 known genetic diseases. Those that result from simple mutations of single genes are often referred to as hereditary diseases, and they exhibit distinctive patterns of inheritance in families.
Inherited diseases result primarily or exclusively from genetic mutations or genetic imbalance passed on from parent to child at conception. These include Mendelian genetic conditions as well as chromosomal abnormalities. A third group of disorders exists wherein both the environment and genetic factors interact to produce—or influence the course of a disease. These conditions to as having multifactorial or complex inheritance patterns.
Some chromosomal conditions are caused by changes in the number of chromosomes. These changes are not inherited, but occur as random events during the formation of reproductive cells (eggs and sperm). An error in cell division called non-disjunction results in reproductive cells with an abnormal number of chromosomes. For example, a reproductive cell may accidentally gain or lose one copy of a chromosome. If one of these atypical reproductive cells contributes to the genetic makeup of a child, the child will have an extra or missing chromosome in each of the body’s cells.
Normally, humans have 23 pairs of chromosomes – making 46 in total. This includes one pair of chromosomes which are the sex chromosomes. The ova and the sperm each carry 23 chromosomes.
- Numerical Aberrations
- Structural Aberrations
- These are usually caused by a failure of chromosome division, which results in cells with an extra chromosome or a deficiency in chromosomes.
- Gametes with these anomalies can result in conditions such as Down syndrome (who have 47 chromosomes instead of 46), or Turner syndrome (45 chromosomes). Common types of numerical aberrations are: triploidy, trisomy, monosomy and mosaicism.
These occur due to a loss or genetic material, or a rearrangement in the location of the genetic material..
- Ring formation
Wolf-Hirschhorn syndrome is caused by the deletion of the distal short arm of chromosome 4. The disorder’s major features include a characteristic facial appearance, delayed growth and development, intellectual disability, and seizures.
Jacobsen syndrome, also known as 11q deletion disorder, results from a loss of genetic material from the end of the long arm of chromosome 11. Signs and symptoms of this condition vary, but most individuals experience delayed development in motor skills and speech, cognitive impairments, learning difficulties, and some behavioral problems.
Angelman syndrome (AS) is an example of genomic imprinting, where the deletion or inactivitation of genes on the maternally inherited chromosome 15 causes the paternal copy, which may be of normal sequence, to be imprinted and silenced. AS is characterized by intellectual and developmental delays, sleep disturbances, seizures, and jerky movements, but also frequent laughter or smiling and usually have a happy demeanor.
Turner syndrome (TS) occurs when one of the two X chromosomes in females is either missing or incomplete. The most common symptoms are short stature and gonadal dysgenesis, which can cause incomplete sexual development and ovarian failure and infertility. As of right now, there is no known cause of TS.
22q11.2 deletion syndrome:
22q11.2 deletion syndrome is caused by the deletion of a small piece of chromosome 22 near the middle of the chromosome. Because signs and symptoms of 22q11.2 deletion syndrome are varied, different groupings of symptoms were once described as completely separate conditions, named DiGeorge syndrome, velocardiofacial syndrome, and conotruncal anomaly face syndrome.
Triple X Syndrome:
Triple X Syndrome is characterized by an extra X chromosome in each of a female’s cells. It does not cause any unusual physical features but is associated with the increased risk of learning disabilities and delayed development of speech and language skills.
Williams syndrome is caused by a deletion of genetic material from portions of the long arm of chromosome 7, a region that consists of more than 25 genes. Researchers have identified a few of the specific genes related to Williams syndrome, but the relationship between most of the genes in the deleted region and the symptoms of Williams syndrome is still unknown.
Cri du Chat Syndrome:
Cri du Chat syndrome results from missing a piece of chromosome 5. Symptoms include a high-pitched cry that sounds like a cat, downward slant of the eyes, partial webbing or fusing of fingers or toes, and slow or incomplete development of motor skills.
Trisomy 13/Patau syndrome:
Trisomy 13, also called Patau syndrome, is a disorder in which an individual has three copies of genetic material from chromosome 13, rather than two. It can occur in three forms: Trisomy 13, which has a third chromosome 13 in all cells; Trisomy 13 mosaicism, which has a third chromosome 13 in some cells; and partial Trisomy, which has the presence of part of an extra chromosome 13 in the cells.
Trisomy 18/Edwards syndrome:
Trisomy 18, or Edwards syndrome, occurs when a person has a third copy of material from chromosome 18 instead of the usual two copies. Some symptoms include clenched hands, feet with a rounded bottom, mental deficiency, underdeveloped fingernails, and an unusual shaped chest.
Cat eye syndrome:
For individuals with cat eye syndrome, the short arm (known as 22p) and a small region of the long arm (22q) of chromosome 22 are present three or four times, rather than twice. Characteristic features of the disorder include mild growth delays before birth, mild mental deficiency, and malformations of the skill and facial region, the heart, the kidneys, and/or the anal region.”
Full Trisomy 16 occurs when an individual has three copies of chromosome 16 instead of the usual two and is the most common chromosomal cause of miscarriage during the pregnancy’s first trimester. Mosaic Trisomy 16 is a rare disorder in which an extra chromosome 16 is present in some cells, but not all. Some common symptoms include intrauterine growth retardation (IUGR) and congenital heart defects.
Charcot-Marie-Tooth (CMT) disease is the most common inherited neurological disorder and is caused by genetic mutations. CMT1A results from a duplication of the gene on chromosome 17 that carries instructions for producing the peripheral myelin protenin-22.
14. Down syndrome:
Down syndrome (DS or DNS), also known as trisomy 21, is a genetic disorder caused by the presence of all or part of a third copy of chromosome 21.
Autosomal dominant diseases:
Normally there are two working copies of every gene in each individual. In the case of a dominant genetic disease, one copy of the gene is altered by mutation and causes the disease even though the other gene copy is normal. . Examples of autosomal dominant diseases include achondroplasia (a form of dwarfism), neurofibromatosis, and Huntington disease.
Autosomal recessive diseases:
In autosomal recessive diseases, both parents must be carriers (i.e., they are clinically normal but have one mutation of a particular gene), and both must pass the mutation to a child in order for that child to be affected Examples of autosomal recessive disease include sickle cell anemia, cystic fibrosis, Tay-Sachs disease, and phenylketonuria.
Sex linked diseases:
When diseases can be attributed to genes on a sex chromosome, either the X or the Y, they are characterized as sex-linked diseases. Human males carry one X and one Y chromosome, and human females carry two X chromosomes. For example Haemophilia (A and B)
When there is interaction between genetic and non-genetic factors, the disease termed is known as multifactorial or polygenic diseases. Examples include hypertension, stroke, diabetes and most forms of mental illness.