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Autism is a spectrum or range of disorders and no exact cause is known. There are several interacting causes that may lead to Autism Spectrum Disorders (ASD). In most cases there is a combination of genetic risk factors that can interact with environmental risk factors. Because of the complexity of the disorder and because of the overlapping of symptoms making each autistic individual unique, the exact cause is difficult to determine.
There are several identified susceptibility genes that raise the risk of autism. Many genes likely contribute to autism. These specific genes are believed to interact with certain environmental factors. Exposure to environmental agents such as infectious agents or chemical agents (including medications and environmental toxins) during pregnancy can cause autism.
About 10-15% of cases have a specific, identifiable genetic cause and other congenital disorders, such as such as Fragile X Syndrome, Tuberous Sclerosis, and Angelman’s Syndrome. The role of the immune system in causation of autism is also gaining importance. It is, however, clear from research that autism is not caused by bad parenting.
Much evidence supports the idea that genetic factors could contribute to a risk of autism. Current evidence suggests that as many as 12 or more genes on different chromosomes may be involved in autism. Each of these are involved in various degrees. Some genes may place a person at greater risk for autism, called susceptibility while yet others may cause specific symptoms or determine severity of the symptoms. Some genes with changes or mutations might add to the symptoms of autism.
The idea of genes being responsible for autism gains support from the facts like identical twins have a high risk of having ASD (36-95% of the time). In non-identical twins, if one child has an ASD, then the other is affected about 0-31% of the time. In addition, parents who have a child with an ASD have a 2%–18% chance of having a second child who is also affected.
Some other genetic conditions also raise the risk of autism. Around 10% of autistic children also have other genetic conditions such as Fragile X syndrome, Tuberous sclerosis, Down’s syndrome and other chromosomal disorders.
HOXA1, of autosomal recessive inheritance is only one of many genes involved in the spectrum of autism disorders. There may be involvement of the DbetaH (DBH) gene as well. These children have a low level of serum dopamine β-hydroxylase, which catalyzes the conversion of dopamine to norepinephrine.
Other suspected genes include NLGN3, NLGN4, NRXN1, MeCP2 etc. The Fragile X gene is associated with autism disorders and there is a positive association of the FMR-1 gene with autism. Mutations or changes in the SHANK2 synaptic scaffolding gene have been documented in autism. In addition, the Reelin gene has been associated with autism. This gene helps in lamination of the brain during the fetal life and helps in cell signalling in adult life.
Research has also shown that environmental factors, such as viruses, may also play a role in causing autism. Infections that appear to be causally related to the development of autism include encephalitis caused by measles, congenital rubella, herpes simplex virus, mumps, varicella, cytomegalovirus, and Stealth virus.
Rubella virus was the first known cause of autism. It was found later that measles and mumps viruses can cause encephalitis that can result in autism later. The infections may usually affect the fetus while in the mother’s womb.
To date, there is no conclusive scientific evidence that any part of a vaccine or any combination of vaccines causes autism. There is also no proof that any material used to make or preserve vaccines plays a role in causing autism. This follows the fears that a vaccine preservative Thimerosal is responsible for autism.
When taken during pregnancy, the prescription drugs valproic acid and thalidomide have been linked with a higher risk of ASDs. Injury with thalidomide occurs early in pregnancy (within 20 to 24 days of conception). Misoprostol, a prostaglandin analogue used for prevention of gastric ulcers and to cause abortions is also implicated. Valproic acid given to epileptic patients may also raise the risk of autism when given in pregnant epileptic mothers.
Acetaminophen has also been suggested to cause autism. Children who were given acetaminophen after the MMR (Measles mumps and rubella) vaccine have been seen to be more likely to become autistic than children given ibuprofen.
A small number of children who are born prematurely or with low birth weight may be at a greater risk for ASDs. Around 35% of individuals with autism have other disorders like depression, bipolar affective disorder, schizophrenia, schizoaffective disorder, Tourette syndrome, tics, Pica, epilepsy, hypothyroidism (underactive thyroid function), Down’s syndrome, and high blood pressure.
There may be metabolic disorders like phenylketonuria (PKU) or histidinemia, the Landau-Kleffner and Rett syndromes and a variety of other conditions that affect brain development and function.
Genetic syndromes like Fragile X syndrome, Angelman’s syndrome, Down, Edwards, and Klinefelter syndromes associated with XXY genotype and may raise the risk of autism according to some studies.
Classical mitochondrial diseases occur in some autistic individuals. Mitochondrial dysfunction is thought to be caused by environmental toxins and could be related to autism.
It is possible that autism results from more than one cause. While defective genes may play an important role, the manifestations and severity of the condition often depends on other factors. Some of these could be the advancing age of the parents, and inflammation of the brain, defective immune systems and responses, immune response of the mother to a viral or bacterial infection, a premature birth, encephalitis in the child after birth, or environmental toxins.