Only one mutated copy of the gene is necessary for a person to be affected by an autosomal dominant disorder. Each affected person usually has one affected parent. The chance a child will inherit the mutated gene is 50%. Examples of this type of disorder are:

• Huntington's disease

• Neurofibromatosis type 1 / 2

• Marfan syndrome

• Hereditary nonpolyposis colorectal cancer

• Heriditary multiple exotoses

• Tuberculous sclerosis

• Von Willebrant disease

• Acute intermittent porphyria

Two copies of the gene must be mutated for a person to be affected by an autosomal recessive disorder. An affected person usually has unaffected parents who each carry a single copy of the mutated gene and are referred to as genetic carriers. Two unaffected people who each carry one copy of the mutated gene have a 25% risk with each pregnancy of having a child affected by the disorder. Examples of this type of disorder are:

• Albinism

• Cystic fibrosis

• Sickle cell disease

• Tay-Sachs disease

• Spinal muscular atrophy

• Roberts syndrome

Certain other phenotypes, such as wet versus dry earwax, are also determined in an autosomal recessive fashion. Some autosomal recessive disorders are common because, in the past, carrying one of the faulty genes led to some protection against an infectious disease such as tuberculosis or malaria e.g. sickle cell, cystic fibrosis, PKU, thalassaemia.

• X-linked dominant disorders are caused by mutations in genes on the X chromosome. Only a few disorders have this inheritance pattern, with a prime example being X-linked hypophosphatemic rickets. Males and females are both affected in these disorders, with males typically being more severely affected than females. Some X-linked dominant conditions, such as Rett syndrome, incontinentia pigmenti type 2, and Aicardi syndrome, are usually fatal in males either in utero or shortly after birth, and are therefore predominantly seen in females. Exceptions to this finding are extremely rare cases in which boys with Klinefelter syndrome (44+xxy) also inherit an X-linked dominant condition and exhibit symptoms more similar to those of a female in terms of disease severity. The chance of passing on an X-linked dominant disorder differs between men and women. The sons of a man with an X-linked dominant disorder will all be unaffected (since they receive their father's Y chromosome), but his daughters will all inherit the condition. A woman with an X-linked dominant disorder has a 50% chance of having an affected fetus with each pregnancy, although in cases such as incontinentia pigmenti, only female offspring are generally viable.

X-linked recessive conditions are also caused by mutations in genes on the X chromosome. Males are much more frequently affected than females, because they only have the one X chromosome necessary for the condition to present. The chance of passing on the disorder differs between men and women. The sons of a man with an X-linked recessive disorder will not be affected (since they receive their father's Y chromosome), but his daughters will be carriers of one copy of the mutated gene. A woman who is a carrier of an X-linked recessive disorder (XRXr) has a 50% chance of having sons who are affected and a 50% chance of having daughters who are carriers of one copy of the mutated gene. X-linked recessive conditions include the serious diseases hemophilia A, Duchenne muscular dystrophy, and Lesch–Nyhan syndrome, as well as common and less serious conditions such as male pattern baldness and red–green color blindness. X-linked recessive conditions can sometimes manifest in females due to skewed X-inactivation or monosomy X (Turner syndrome).

Y-linked disorders are caused by mutations on the Y chromosome. These conditions may only be transmitted from the heterogametic sex (e.g. male humans) to offspring of the same sex. More simply, this means that Y-linked disorders in humans can only be passed from men to their sons; females can never be affected because they do not possess Y-allosomes.

Y-linked disorders are exceedingly rare but the most well-known examples typically cause infertility. Reproduction in such conditions is only possible through the circumvention of infertility by medical intervention.

This type of inheritance, also known as maternal inheritance, is the rarest and applies to the 13 genes encoded by mitochondrial DNA. Because only egg cells contribute mitochondria to the developing embryo, only mothers (who are affected) can pass on mitochondrial DNA conditions to their children. An example of this type of disorder is Leber's hereditary optic neuropathy.

It is important to stress that the vast majority of mitochondrial diseases (particularly when symptoms develop in early life) are actually caused by a nuclear gene defect, as the mitochondria are mostly developed by non-mitochondrial DNA. These diseases most often follow autosomal recessive inheritance.

Down syndrome or Down's syndrome, also known as trisomy 21, is a genetic disorder caused by the presence of all or part of a third copy of chromosome 21.[2] It is usually associated with physical growth delays, mild to moderate intellectual disability, and characteristic facial features.[1] The average IQ of a young adult with Down syndrome is 50, equivalent to the mental ability of an eight- or nine-year-old child, but this can vary widely.[12][8]

The parents of the affected individual are usually genetically normal.[13] The probability increases from less than 0.1% in 20-year-old mothers to 3% in those of age 45.[3] The extra chromosome is believed to occur by chance, with no known behavioral activity or environmental factor that changes the probability.[14] Down syndrome can be identified during pregnancy by prenatal screening followed by diagnostic testing or after birth by direct observation and genetic testing.[5] Since the introduction of screening, Down syndrome pregnancies are often aborted.[15][16]

There is no cure for Down syndrome.[17] Education and proper care have been shown to improve quality of life.[6] Some children with Down syndrome are educated in typical school classes, while others require more specialized education.[7] Some individuals with Down syndrome graduate from high school, and a few attend post-secondary education.[18] In adulthood, about 20% in the United States do paid work in some capacity,[19] with many requiring a sheltered work environment.[7] Support in financial and legal matters is often needed.[9] Life expectancy is around 50 to 60 years in the developed world with proper health care.[8][9] Regular screening for health problems common in Down syndrome is recommended throughout the person's life.[8]

Down syndrome is one of the most common chromosome abnormalities in humans.[8] It occurs in about 1 in 1,000 babies born each year.[1] In 2015, Down syndrome was present in 5.4 million individuals globally and resulted in 27,000 deaths, down from 43,000 deaths in 1990.[10][11][20] It is named after British doctor John Langdon Down, who fully described the syndrome in 1866.[21] Some aspects of the condition were described earlier by French psychiatrist Jean-Étienne Dominique Esquirol in 1838 and French physician Édouard Séguin in 1844.[22] The genetic cause of Down syndrome was discovered in 1959.[21]

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Alzheimer’s dementia is more common in people with Down syndrome and occurs much earlier in age, as early as 30 years, with a mean age of onset being 52 years. Most people with Down's syndrome will have the Alzheimer's hallmark clumps of amyloid and tau proteins in their brain by the age of 40, and two thirds will have Alzheimer's by the age of 60. Many people first present with behavioural changes rather than cognitive decline but memory and orientation can also be affected early on.

Resources:

MacLennan S. Down’s syndrome. InnovAiT 2020; 13(1): 47–52.

Alzheimer's Society. Understanding what causes the increased risk of Alzheimer’s disease in Down’s syndrome.

Patau syndrome is a syndrome caused by a chromosomal abnormality, in which some or all of the cells of the body contain extra genetic material from chromosome 13. The extra genetic material disrupts normal development, causing multiple and complex organ defects.

This can occur either because each cell contains a full extra copy of chromosome 13 (a disorder known as trisomy 13 or trisomy D or T13[1]), or because each cell contains an extra partial copy of the chromosome or because there are two different lines of cells - one healthy with the correct number of chromosomes 13 and one that contains an extra copy of the chromosome- mosaic Patau syndrome. Full trisomy 13 is caused by nondisjunction of chromosomes during meiosis (the mosaic form is caused by nondisjunction during mitosis).

Like all nondisjunction conditions (such as Down syndrome and Edwards syndrome), the risk of this syndrome in the offspring increases with maternal age at pregnancy, with about 31 years being the average.[2] Patau syndrome affects somewhere between 1 in 10,000 and 1 in 21,700 live births.[3]