A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders are the most common, the term is mostly used when discussing disorders with a single genetic cause, either in a gene or chromosome. The mutation responsible can occur spontaneously before embryonic development (a de novo mutation), or it can be inherited from two parents who are carriers of a faulty gene (autosomal recessive inheritance) or from a parent with the disorder (autosomal dominant inheritance). When the genetic disorder is inherited from one or both parents, it is also classified as a hereditary disease. Some disorders are caused by a mutation on the X chromosome and have X-linked inheritance. Very few disorders are inherited on the Y chromosome or mitochondrial DNA.
There are well over 6,000 known genetic disorders, and new genetic disorders are constantly being described in medical literature. More than 600 of these disorders are treatable. Around 1 in 50 people are affected by a known single-gene disorder, while around 1 in 263 are affected by a chromosomal disorder. Around 65% of people have some kind of health problem as a result of congenital genetic mutations. Due to the significantly large number of genetic disorders, approximately 1 in 21 people are affected by a genetic disorder classified as "rare" (usually defined as affecting less than 1 in 2,000 people). Most genetic disorders are rare in themselves.
All genetic disorders are present before birth, and some genetic disorders produce birth defects, but many birth defects are developmental rather than hereditary. The opposite of a hereditary disease is an acquired disease. Most cancers, although they involve genetic mutations to a small proportion of cells in the body, are acquired diseases. Some family cancer syndromes, such as BRCA mutations, are hereditary genetic disorders.
Inheritable disorders may be of several patterns, determined by two principle factors: (1) whether the gene is dominant or recessive and (2) whether the gene is on one of the 46 ordinary (autosomal) chromosomes or a sex (X or Y) chromosome.
Dominant genes express themselves even if only one of a pair of alleles is present. Recessive genes only express themselves if there is a pair on autosomes or X chromosomes in females, or the gene is on the X chromosome in males.
When both parents carry one defective gene, each of their children faces one in four chance of developing an autosomal recessive disease. At the same time, each child also faces a one in two chance of inheriting just one copy of the defective gene. Individuals who have only one defective gene are known as carriers, meaning they do not develop the disease, but they can pass the gene on to their own children. In autosomal dominant inheritance, all people who inherit a single copy of the disease gene develop the disease. As a result, there are no unaffected carriers of the gene.
In real life, the distinction between dominance and recessiveness is usually not black-and-white; or, to continue with the example above, not black and blond. One allele often does not completely dominate the other, and the presence of a different gene may affect the final expression. Thus, a person with one gene for black hair and one for blond may actually have somewhat lighter hair than someone who has both genes coding for black hair.
Autosomal refers to the fact that the genetic defect may be located on any of the 46 rodlike structures, called chromosomes, that hold the genes found in each human cell, except the two that determine a person's sex. Diseases with an autosomal dominant pattern means that a child need only inherit the defective gene from one parent in order to have the disease. The parent transmitting the gene also has the disorder, and each of his or her children has a 50 percent chance of inheriting the disease. With an autosomal inheritance pattern, male and female children are equally affected. the responsible gene and thus having HHT. Children who do not inherit the gene will not be affected nor will they pass the gene on to their children.
Recessive patterns of inheritance can be autosomal or X-linked. A disease governed by the recessive pattern requires that both parents, who usually do not have the disease, pass on the defective gene in order for a child to be affected by the disease. Each child of such parents has a 25 percent chance of inheriting and showing signs of the disease. A 50 percent chance exists that such a child will inherit the defective gene from only one parent and, therefore, will be a carrier of the flawed gene and will usually not show signs of the disease.
X-linked refers to a gene that is on the X chromosome, which along with the Y chromosome determines sex. Male children have one X chromosome and one Y chromosome, while females have two X chromosomes. Therefore, inheritance of a gene on the X chromosome is different from that for one on an autosomal chromosome. In the X-linked recessive pattern, the disease develops mostly in males. Females who inherit the defective gene are usually carriers like their mothers and can pass the disease on to their sons but rarely show signs of the disease themselves.
For many X-linked dominant medical conditions, females may not be as severely affected as males, since females have the other allele on their other X chromosome to counteract the effects. An example of a condition that can be inherited in an X-linked dominant fashion is Alport syndrome, which involves progressive hearing loss and progressive kidney problems. If a woman has Alport syndrome, she may only have mild hearing and kidney problems. Each of her children has a 50-50 chance of inheriting the condition, but it will be more severe in her sons. If a man has the X-linked form of Alport syndrome, all of his daughters will also have it, but none of his sons will have it.
In the USA, 50% of the heart disease cases come from 5% of the families. In a study of 25,000 families in Texas, only 3,000 (12%) of them were seriously at risk of heart disease, strokes or cancer.