82-419: 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 . It is usually associated with developmental delays, mild to moderate intellectual disability , and characteristic physical features. The parents of the affected individual are usually genetically normal. The incidence of the syndrome increases with
164-427: A Robertsonian translocation , isochromosome , or ring chromosome . These contain additional material from chromosome 21 and occur in about 2.5% of cases. An isochromosome results when the two long arms of a chromosome separate together rather than the long and short arm separating together during egg or sperm development . Down syndrome (also known by the karyotype 47,XX,+21 for females and 47,XY,+21 for males)
246-477: A single crease of the palm , and short fingers. Instability of the atlantoaxial joint occurs in about 1–2%. Atlantoaxial instability may cause myelopathy due to cervical spinal cord compression later in life, this often manifests as new onset weakness, problems with coordination , bowel or bladder incontinence, and gait dysfunction. Serial imaging cannot reliably predict future cervical cord compression, but changes can be seen on neurological exam. The condition
328-443: A small chin , epicanthic folds , low muscle tone , a flat nasal bridge , and a protruding tongue. A protruding tongue is caused by low tone and weak facial muscles, and often corrected with myofunctional exercises. Some characteristic airway features can lead to obstructive sleep apnea in around half of those with Down syndrome. Other common features include: excessive joint flexibility, extra space between big toe and second toe,
410-499: A 1% possibility of having a second child with the syndrome, if both parents are found to have normal karyotypes . The extra chromosome content can arise through several different ways. The most common cause (about 92–95% of cases) is a complete extra copy of chromosome 21, resulting in trisomy 21. In 1–2.5% of cases, some of the cells in the body are normal and others have trisomy 21, known as mosaic Down syndrome. The other common mechanisms that can give rise to Down syndrome include:
492-445: A child affected by the disorder. Examples of this type of disorder are albinism , medium-chain acyl-CoA dehydrogenase deficiency , cystic fibrosis , sickle cell disease , Tay–Sachs disease , Niemann–Pick disease , spinal muscular atrophy , and 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
574-540: A child with Down syndrome when the mother is affected and a less than 5% probability if the father is affected. The probability of this type of Down syndrome is not related to the mother's age. Some children without Down syndrome may inherit the translocation and have a higher probability of having children of their own with Down syndrome. In this case it is sometimes known as familial Down syndrome. The extra genetic material present in Down syndrome results in overexpression of
656-474: A false-positive rate of 2–5%. If Down syndrome occurs in one in 500 pregnancies with a 90% detection rate and the test used has a 5% false-positive rate, this means, of 20 women who test positive on screening, only one will not have a fetus with Down syndrome confirmed. If the screening test has a 2% false-positive rate, this means, of 50 women who test positive on screening, one will not have a fetus with Down syndrome. Genetic disorder A genetic disorder
738-650: 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 (due to their size). There are well over 6,000 known genetic disorders, and new genetic disorders are constantly being described in medical literature. More than 600 genetic disorders are treatable. Around 1 in 50 people are affected by
820-577: 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 foetus 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
902-468: A few attend post-secondary education . In adulthood, about 20% in the United States do some paid work, with many requiring a sheltered work environment. Caretaker support in financial and legal matters is often needed. Life expectancy is around 50 to 60 years in the developed world , with proper health care. Regular screening for health issues common in Down syndrome is recommended throughout
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#1732790655526984-447: A gene into the potentially trillions of cells that carry the defective copy. Finding an answer to this has been a roadblock between understanding the genetic disorder and correcting the genetic disorder. 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
1066-418: A genetic disorder rests on the inheritance of genetic material. With an in depth family history , it is possible to anticipate possible disorders in children which direct medical professionals to specific tests depending on the disorder and allow parents the chance to prepare for potential lifestyle changes, anticipate the possibility of stillbirth , or contemplate termination . Prenatal diagnosis can detect
1148-619: 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 cancer syndromes , however, such as BRCA mutations , are hereditary genetic disorders. A single-gene disorder (or monogenic disorder ) is the result of a single mutated gene. Single-gene disorders can be passed on to subsequent generations in several ways. Genomic imprinting and uniparental disomy , however, may affect inheritance patterns. The divisions between recessive and dominant types are not "hard and fast", although
1230-476: A high likelihood of trisomy 21. Accuracy has been reported at 98.6% in the first trimester of pregnancy. Confirmatory testing by invasive techniques (amniocentesis, CVS) is still required to confirm the screening result. For combinations of ultrasonography and non-genetic blood tests, screening in both the first and second trimesters is better than just screening in the first trimester. The different screening techniques in use are able to pick up 90–95% of cases, with
1312-636: 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. Genetic disorders are present before birth, and some genetic disorders produce birth defects , but birth defects can also be developmental rather than hereditary . The opposite of
1394-514: A lower risk of hardening of the arteries . Although the overall risk of cancer in Down syndrome is not changed, the risk of testicular cancer and certain blood cancers, including acute lymphoblastic leukemia (ALL) and acute megakaryoblastic leukemia (AMKL) is increased while the risk of other non-blood cancers is decreased. People with Down syndrome are believed to have an increased risk of developing cancers derived from germ cells whether these cancers are blood- or non-blood-related. In 2008,
1476-410: A male affected with Down syndrome, it results in a karyotype of 46XY,t(14q21q). This may be a new mutation or previously present in one of the parents. The parent with such a translocation is usually normal physically and mentally; however, during production of egg or sperm cells, a higher chance of creating reproductive cells with extra chromosome 21 material exists. This results in a 15% chance of having
1558-788: A more alkaline saliva resulting in a greater resistance to tooth decay , despite decreased quantities of saliva, less effective oral hygiene habits, and higher plaque indexes. Higher rates of tooth wear and bruxism are also common. Other common oral manifestations of Down syndrome include enlarged hypotonic tongue, crusted and hypotonic lips, mouth breathing , narrow palate with crowded teeth, class III malocclusion with an underdeveloped maxilla and posterior crossbite , delayed exfoliation of baby teeth and delayed eruption of adult teeth, shorter roots on teeth, and often missing and malformed (usually smaller) teeth. Less common manifestations include cleft lip and palate and enamel hypocalcification (20% prevalence). Taurodontism , an elongation of
1640-404: A normal number of lymphocytes and produce less antibodies which is said to present an increased risk of infection. Down syndrome is associated with an increased risk of some chronic diseases that are typically associated with older age such as Alzheimer's disease. It is believed that accelerated aging occurs and increases the biological age of tissues, but molecular evidence for this hypothesis
1722-787: 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%. Autosomal dominant conditions sometimes have reduced penetrance , which means although only one mutated copy is needed, not all individuals who inherit that mutation go on to develop the disease. Examples of this type of disorder are Huntington's disease , neurofibromatosis type 1 , neurofibromatosis type 2 , Marfan syndrome , hereditary nonpolyposis colorectal cancer , hereditary multiple exostoses (a highly penetrant autosomal dominant disorder), tuberous sclerosis , Von Willebrand disease , and acute intermittent porphyria . Birth defects are also called congenital anomalies. Two copies of
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#17327906555261804-467: A poorly or nonfunctioning thyroid at birth (known as congenital hypothyroidism ) which occurs in 1% or can develop later due to an attack on the thyroid by the immune system resulting in Graves' disease or autoimmune hypothyroidism . Type 1 diabetes mellitus is also more common. Constipation occurs in nearly half of people with Down syndrome and may result in changes in behavior. One potential cause
1886-576: A portion of the 310 genes located on chromosome 21. This overexpression has been estimated at 50%, due to the third copy of the chromosome present. Some research has suggested the Down syndrome critical region is located at bands 21q22.1–q22.3, with this area including genes for the amyloid precursor protein , superoxide dismutase , and likely the ETS2 proto oncogene . Other research, however, has not confirmed these findings. MicroRNAs are also proposed to be involved. The dementia that occurs in Down syndrome
1968-599: A third of cases of intellectual disability. Many developmental milestones are delayed with the ability to crawl typically occurring around 8–22 months rather than 6–12 months, and the ability to walk independently typically occurring around 1–4 years rather than 9–18 months. Walking is acquired in 50% of children after 24 months. Most individuals with Down syndrome have mild (IQ: 50–69) or moderate (IQ: 35–50) intellectual disability with some cases having severe (IQ: 20–35) difficulties. Those with mosaic Down syndrome typically have IQ scores 10–30 points higher than that. As they age,
2050-507: A wide range of emotions. While people with Down syndrome are generally happy, symptoms of depression and anxiety may develop in early adulthood. Children and adults with Down syndrome are at increased risk of epileptic seizures , which occur in 5–10% of children and up to 50% of adults. This includes an increased risk of a specific type of seizure called infantile spasms . Many (15%) who live 40 years or longer develop Alzheimer's disease . In those who reach 60 years of age, 50–70% have
2132-462: Is Hirschsprung's disease , occurring in 2–15%, which is due to a lack of nerve cells controlling the colon . Other congenital problems can include duodenal atresia , imperforate anus and gastroesophageal reflux disease . Celiac disease affects about 7–20%. People with Down syndrome tend to be more susceptible to gingivitis as well as early, severe periodontal disease, necrotising ulcerative gingivitis , and early tooth loss , especially in
2214-465: 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. Genetic disorders may also be complex, multifactorial, or polygenic, meaning they are likely associated with
2296-531: 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 chromosome 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
2378-494: Is a leukemia of megakaryoblasts , the precursors cells to megakaryocytes which form blood platelets . Acute lymphoblastic leukemia in Down syndrome accounts for 1–3% of all childhood cases of ALL. It occurs most often in those older than nine years or having a white blood cell count greater than 50,000 per microliter and is rare in those younger than one year old. ALL in Down syndrome tends to have poorer outcomes than other cases of ALL in people without Down syndrome. In short,
2460-405: Is also a strong environmental component to many of them (e.g., blood pressure ). Other such cases include: A chromosomal disorder is a missing, extra, or irregular portion of chromosomal DNA. It can be from an atypical number of chromosomes or a structural abnormality in one or more chromosomes. An example of these disorders is Trisomy 21 (the most common form of Down syndrome ), in which there
2542-423: Is also considered a recessive condition, but heterozygous carriers have increased resistance to malaria in early childhood, which could be described as a related dominant condition. When a couple where one partner or both are affected or carriers of a single-gene disorder wish to have a child, they can do so through in vitro fertilization, which enables preimplantation genetic diagnosis to occur to check whether
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2624-412: Is an extra copy of chromosome 21 in all cells. Due to the wide range of genetic disorders that are known, diagnosis is widely varied and dependent of the disorder. Most genetic disorders are diagnosed pre-birth , at birth , or during early childhood however some, such as Huntington's disease , can escape detection until the patient begins exhibiting symptoms well into adulthood. The basic aspects of
2706-447: Is due to an excess of amyloid beta peptide produced in the brain and is similar to Alzheimer's disease , which also involves amyloid beta build-up. Amyloid beta is processed from amyloid precursor protein, the gene for which is located on chromosome 21. Senile plaques and neurofibrillary tangles are present in nearly all by 35 years of age, though dementia may not be present. It is hypothesized that those with Down syndrome lack
2788-407: Is more accurate. Increased fetal nuchal translucency (NT) indicates an increased possibility of Down syndrome picking up 75–80% of cases and being falsely positive in 6%. Several blood markers can be measured to predict the chances of Down syndrome during the first or second trimester. Testing in both trimesters is sometimes recommended and test results are often combined with ultrasound results. In
2870-406: Is more common with Down syndrome, though the rate may not differ until after twelve months of age compared to children without Down syndrome. Early screening is recommended to identify and treat significant refractive error with glasses or contact lenses. Poor accommodation (ability to focus on close objects) is associated with Down syndrome, which may mean bifocals are indicated. In keratoconus ,
2952-442: Is more often acquired than congenital . Early diagnosis and treatment of strabismus reduces the risk of vision loss from amblyopia. In Down syndrome, the presence of epicanthal folds may give the false impression of strabismus , referred to as pseudostrabismus . Nasolacrimal duct obstruction, which causes tearing ( epiphora ), is more frequently bilateral and multifactorial than in children without Down syndrome. Refractive error
3034-424: Is mostly caused by a failure of the 21st chromosome to separate during egg or sperm development, known as nondisjunction . As a result, a sperm or egg cell is produced with an extra copy of chromosome 21; this cell thus has 24 chromosomes. When combined with a normal cell from the other parent, the baby has 47 chromosomes, with three copies of chromosome 21. About 88% of cases of trisomy 21 result from nonseparation of
3116-421: 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
3198-416: Is opposed to the more traditional phenotype-first approach, and may identify causal factors that have previously been obscured by clinical heterogeneity , penetrance , and expressivity. On a pedigree, polygenic diseases do tend to "run in families", but the inheritance does not fit simple patterns as with Mendelian diseases. This does not mean that the genes cannot eventually be located and studied. There
3280-403: Is sparse. According to a biomarker of tissue age known as epigenetic clock , it is hypothesized that trisomy 21 increases the age of blood and brain tissue (on average by 6.6 years). Guidelines recommend screening for Down syndrome to be offered to all pregnant women, regardless of age. A number of tests are used, with varying levels of accuracy. They are typically used in combination to increase
3362-510: Is surgically corrected with spine surgery. Growth in height is slower, resulting in adults who tend to have short stature —the average height for men is 154 centimetres (5 feet 1 inch), and for women is 142 centimetres (4 feet 8 inches). Individuals with Down syndrome are at increased risk for obesity as they age due to hypothyroidism, other medical issues and lifestyle. Growth charts have been developed specifically for children with Down syndrome. This syndrome causes about
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3444-506: Is typically preceded by transient myeloproliferative disease (TMD), a disorder of blood cell production in which non-cancerous megakaryoblasts with a mutation in the GATA1 gene rapidly divide during the later period of pregnancy. GATA1 mutations combined with trisomy 21 contribute to a predisposition to TAM. In trisomy 21, the process of leukemogenesis starts in early fetal life, with genetic factors, including GATA1 mutations, contributing to
3526-510: The cornea progressively thins and bulges into a cone shape, causing visual blurring or distortion. Keratoconus first presents in the teen years and progresses into the thirties. Down syndrome is a strong risk factor for developing keratoconus, and onset may be occur at a younger age than in those without Down syndrome. Eye rubbing is also a risk factor for developing keratoconus. It is speculated that chronic eye irritation from blepharitis may increase eye rubbing in Down syndrome, contributing to
3608-439: The sensorineural type occurs at a much earlier age and affects 10–70% of people with Down syndrome. The rate of congenital heart disease in newborns with Down syndrome is around 40%. Of those with heart disease, about 80% have an atrial septal defect or ventricular septal defect with the former being more common. Congenital heart disease can also put individuals at a higher risk of pulmonary hypertension , where arteries in
3690-517: The World Health Organization (WHO) introduced a distinct classification for myeloid proliferation in individuals with Down syndrome. Leukemia is 10 to 15 times more common in children with Down syndrome. In particular, acute lymphoblastic leukemia is 20 times more common and the megakaryoblastic form of acute myeloid leukemia ( acute megakaryoblastic leukemia ), is 500 times more common. Acute megakaryoblastic leukemia (AMKL)
3772-399: 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
3854-443: 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
3936-448: The active time of a genetic disorder, patients mostly rely on maintaining or slowing the degradation of quality of life and maintain patient autonomy . This includes physical therapy and pain management . The treatment of genetic disorders is an ongoing battle, with over 1,800 gene therapy clinical trials having been completed, are ongoing, or have been approved worldwide. Despite this, most treatment options revolve around treating
4018-400: The age of the mother, from less than 0.1% for 20-year-old mothers to 3% for those of age 45. It is believed to occur by chance, with no known behavioral activity or environmental factor that changes the probability. Usually, babies get 23 chromosomes from each parent for a total of 46, whereas in Down syndrome, a third 21st chromosome is attached. The extra chromosome is provided at conception as
4100-449: The children of someone with Down syndrome will also have the syndrome. The cause of the extra full or partial chromosome is still unknown. Most of the time, Down syndrome is caused by a random mistake in cell division during early development of the fetus, but not inherited, and there is no scientific research which shows that environmental factors or the parents' activities contribute to Down syndrome. The only factor that has been linked to
4182-444: The chromosomes in the mother, 8% from nonseparation in the father, and 3% after the egg and sperm have merged. Mosaic Down syndrome is diagnosed when there is a mixture of two types of cells: some cells have three copies of chromosome 21 but some cells have the typical two copies of chromosome 21. This type is the least common form of Down syndrome and accounts for only about 1% of all cases. Children with mosaic Down syndrome may have
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#17327906555264264-525: The detection rate. None can be definitive; thus, if screening predicts a high possibility of Down syndrome, either amniocentesis or chorionic villus sampling is required to confirm the diagnosis. Prenatal ultrasound can be used to screen for Down syndrome. Findings that indicate increased chances when seen at 14 to 24 weeks of gestation include a small or no nasal bone, large ventricles , nuchal fold thickness , and an abnormal right subclavian artery , among others. The presence or absence of many markers
4346-460: The development of TAM on the preleukemic pathway. The condition affects 3–10% of babies with Down. While it often spontaneously resolves within three months of birth, it can cause serious blood, liver, or other complications. In about 10% of cases, TMD progresses to AMKL during the three months to five years following its resolution. People with Down syndrome have a lower risk of all major solid cancers, including those of lung, breast, and cervix, with
4428-460: The disease. Down syndrome regression disorder is a sudden regression with neuropsychiatric symptoms such as catatonia , possibly caused by an autoimmune disease. It primarily appears in teenagers and younger adults. Hearing and vision disorders occur in more than half of people with Down syndrome. Brushfield spots (small white or grayish/brown spots on the periphery of the iris ), upward slanting palpebral fissures (the opening between
4510-440: The divisions between autosomal and X-linked types are (since the latter types are distinguished purely based on the chromosomal location of the gene). For example, the common form of dwarfism , achondroplasia , is typically considered a dominant disorder, but children with two genes for achondroplasia have a severe and usually lethal skeletal disorder, one that achondroplasics could be considered carriers for. Sickle cell anemia
4592-421: The effects of multiple genes in combination with lifestyles and environmental factors. Multifactorial disorders include heart disease and diabetes . Although complex disorders often cluster in families, they do not have a clear-cut pattern of inheritance. This makes it difficult to determine a person's risk of inheriting or passing on these disorders. Complex disorders are also difficult to study and treat because
4674-412: The egg and sperm combine. In 1–2% of cases, the additional chromosome is added in the embryo stage and only impacts some of the cells in the body; this is known as Mosaic Down syndrome . Translocation Down syndrome is another rare type. Down syndrome can be identified during pregnancy by prenatal screening , followed by diagnostic testing, or after birth by direct observation and genetic testing . Since
4756-426: The embryo has the genetic disorder. Most congenital metabolic disorders known as inborn errors of metabolism result from single-gene defects. Many such single-gene defects can decrease the fitness of affected people and are therefore present in the population in lower frequencies compared to what would be expected based on simple probabilistic calculations. Only one mutated copy of the gene will be necessary for
4838-407: The first year of life and are partly due to poor eustachian tube function. Excessive ear wax can also cause hearing loss due to obstruction of the outer ear canal . Even a mild degree of hearing loss can have negative consequences for speech, language understanding, and academics. It is important to rule out hearing loss as a factor in social and cognitive deterioration. Age-related hearing loss of
4920-758: The gap tends to widen between people with Down syndrome and their same-age peers. Commonly, individuals with Down syndrome have better language understanding than ability to speak. Babbling typically emerges around 15 months on average. 10–45% of those with Down syndrome have either a stutter or rapid and irregular speech , making it difficult to understand them. After reaching 30 years of age, some may lose their ability to speak. They typically do fairly well with social skills. Behavior problems are not generally as great an issue as in other syndromes associated with intellectual disability. In children with Down syndrome, mental illness occurs in nearly 30% with autism occurring in 5–10%. People with Down syndrome experience
5002-408: 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 . Each parent with a defective gene normally do not have symptoms. Two unaffected people who each carry one copy of the mutated gene have a 25% risk with each pregnancy of having
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#17327906555265084-453: The increased chance of having a baby with Down syndrome is advanced parental age. This is mostly associated with advanced maternal age but about 10 per cent of cases are associated with advanced paternal age . Down syndrome is caused by having three copies of the genes on chromosome 21 , rather than the usual two. The parents of the affected individual are typically genetically normal. Those who have one child with Down syndrome have about
5166-485: The increased prevalence of keratoconus. An association between glaucoma and Down syndrome is often cited. Glaucoma in children with Down syndrome is uncommon, with a prevalence of less than 1%. It is currently unclear if the prevalence of glaucoma in those with Down syndrome differs from that in the absence of Down syndrome. Estimates of prevalence of ocular findings in Down Syndrome vary widely depending on
5248-510: The introduction of screening, Down syndrome pregnancies are often aborted (rates varying from 50 to 85% depending on maternal age, gestational age, and maternal race/ethnicity). As of 2024, there is no known cure for Down syndrome. Education and proper care have been shown to provide better quality of life . Some children with Down syndrome are educated in typical school classes, while others require more specialized education . Some individuals with Down syndrome graduate from high school , and
5330-422: The likelihood of developing acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) is higher in children with Down syndrome compared to those without Down syndrome. Myeloid leukemia typically precedes Down syndrome and is accompanied by a condition known as transient abnormal myelopoiesis (TAM), which generally disrupts the differentiation of megakaryocytes and erythrocytes. In Down syndrome, AMKL
5412-439: The lower front teeth. While plaque and poor oral hygiene are contributing factors, the severity of these periodontal diseases cannot be explained solely by external factors. Research suggests that the severity is likely a result of a weakened immune system. The weakened immune system also contributes to increased incidence of yeast infections in the mouth (from Candida albicans ). People with Down syndrome also tend to have
5494-485: The lowest relative rates occurring in those aged 50 years or older. This low risk is thought to be due to an increase in the expression of tumor suppressor genes present on chromosome 21. One exception is testicular germ cell cancer which occurs at a higher rate in Down syndrome. Problems of the thyroid gland occur in 20–50% of individuals with Down syndrome. Low thyroid is the most common form, occurring in almost half of all individuals. Thyroid problems can be due to
5576-458: The lungs narrow and cause inadequate blood oxygenation. Some of the genetic contributions to pulmonary hypertension in individuals with Down Syndrome are abnormal lung development, endothelial dysfunction , and proinflammatory genes. Mitral valve problems become common as people age, even in those without heart problems at birth. Other problems that may occur include tetralogy of Fallot and patent ductus arteriosus . People with Down syndrome have
5658-643: The mutated gene. A woman who is a carrier of an X-linked recessive disorder (X X ) 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
5740-1003: The past, carrying one of the faulty genes led to a slight protection against an infectious disease or toxin such as tuberculosis or malaria . Such disorders include cystic fibrosis, sickle cell disease, phenylketonuria and 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
5822-594: The person's life. Down syndrome is the most common chromosomal abnormality , occurring in about 1 in 1,000 babies born worldwide, and one in 700 in the US. In 2015, there were 5.4 million people with Down syndrome globally, of whom 27,000 died, down from 43,000 deaths in 1990. The syndrome is named after British physician John Langdon Down , who fully described it in 1866. Some aspects were described earlier by French psychiatrist Jean-Étienne Dominique Esquirol in 1838 and French physician Édouard Séguin in 1844. The genetic cause
5904-606: The presence of characteristic abnormalities in fetal development through ultrasound , or detect the presence of characteristic substances via invasive procedures which involve inserting probes or needles into the uterus such as in amniocentesis . Not all genetic disorders directly result in death; however, there are no known cures for genetic disorders. Many genetic disorders affect stages of development, such as Down syndrome , while others result in purely physical symptoms such as muscular dystrophy . Other disorders, such as Huntington's disease , show no signs until adulthood. During
5986-651: The pulp chamber, has a high prevalence in people with DS. Males with Down syndrome usually do not father children, while females have lower rates of fertility relative to those who are unaffected. Fertility is estimated to be present in 30–50% of females. Menopause usually occurs at an earlier age. The poor fertility in males is thought to be due to problems with sperm development ; however, it may also be related to not being sexually active. As of 2006, three instances of males with Down syndrome fathering children and 26 cases of females having children have been reported. Without assisted reproductive technologies , around half of
6068-442: The risk of vision loss from amblyopia . Dot-like opacities in the cortex of the lens (cerulean cataract) are present in up to 50% of people with Down syndrome, but may be followed without treatment if they are not visually significant. Strabismus , nystagmus and nasolacrimal duct obstruction occur more frequently in children with Down syndrome. Screening for these diagnoses should begin within six months of birth. Strabismus
6150-433: The same features as other children with Down syndrome. However, they may have fewer characteristics of the condition due to the presence of some (or many) cells with a typical number of chromosomes. The extra chromosome 21 material may also occur due to a Robertsonian translocation in 2–4% of cases. In this translocation Down syndrome, the long arm of chromosome 21 is attached to another chromosome, often chromosome 14 . In
6232-431: The second trimester, often two or three tests are used in combination with two or three of: α-fetoprotein , unconjugated estriol, total hCG, and free βhCG detecting about 60–70% of cases. Testing of the mother's blood for fetal DNA is being studied and appears promising in the first trimester. The International Society for Prenatal Diagnosis considers it a reasonable screening option for those women whose pregnancies are at
6314-423: 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. There are well over 6,000 known genetic disorders, and new genetic disorders are constantly being described in medical literature. The earliest known genetic condition in
6396-401: The specific factors that cause most of these disorders have not yet been identified. Studies that aim to identify the cause of complex disorders can use several methodological approaches to determine genotype – phenotype associations. One method, the genotype-first approach , starts by identifying genetic variants within patients and then determining the associated clinical manifestations. This
6478-530: The study. Some prevalence estimates follow. Vision problems have been observed in 38–80% of cases. Brushfield spots are present in 38–85% of individuals. Between 20 and 50% have strabismus . Cataracts occur in 15%, and may be present at birth. Keratoconus may occur in as many as 21–30%. Hearing problems are found in 50–90% of children with Down syndrome. This is often the result of otitis media with effusion which occurs in 50–70% and chronic ear infections which occur in 40–60%. Ear infections often begin in
6560-442: The symptoms of the disorders in an attempt to improve patient quality of life . Gene therapy refers to a form of treatment where a healthy gene is introduced to a patient. This should alleviate the defect caused by a faulty gene or slow the progression of the disease. A major obstacle has been the delivery of genes to the appropriate cell, tissue, and organ affected by the disorder. Researchers have investigated how they can introduce
6642-536: The upper and lower lids) and epicanthal folds (folds of skin between the upper eyelid and the nose) are clinical signs at birth suggesting the diagnosis of Down syndrome especially in the Western World . None of these requires treatment. Visually significant congenital cataracts (clouding of the lens of the eye) occur more frequently with Down syndrome. Neonates with Down syndrome should be screened for cataract because early recognition and referral reduce
6724-579: Was discovered in 1959. Those with Down syndrome nearly always have physical and intellectual disabilities. As adults, their mental abilities are typically similar to those of an 8- or 9-year-old. At the same time, their emotional and social awareness is very high. They can have poor immune function and generally reach developmental milestones at a later age. They have an increased risk of a number of health concerns, such as congenital heart defect , epilepsy , leukemia , and thyroid diseases . People with Down syndrome may have these physical characteristics:
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