Tiny, Spontaneous Gene Mutations May Boost Autism Risk

Tiny gene mutations, each individually rare, pose more risk for autism than had been previously thought, suggests a study funded in part by the National Institute of Mental Health, a component of the National Institutes of Health.

These spontaneous deletions and duplications of genetic material were found to be ten times more prevalent in sporadic cases of autism spectrum disorders than in healthy control subjects — but only twice as prevalent in autism cases from families with more than one affected member. The results implicate the anomalies as primary, rather than just contributory, causes of the disorder in most cases when they are present, according to the researchers. Although they might share similar symptoms, different cases of autism could thus be traceable to any of 100 or more genes, alone or in combination.

“These structural variations are emerging as a different kind of genetic risk for autism than the more common sequence changes in letters of the genetic code that we’ve been looking for,” explained NIMH director Thomas Insel, M.D. “The best evidence yet that such deletions and duplications are linked to the disorder, these findings certainly complicate the search for genes contributing to autism. These are rare changes, dispersed across the genome, and they tell us that autism may be the final common path for many different genetic abnormalities.”

“Our results show conclusively that these tiny glitches are frequent in autism, occurring in at least ten percent of cases, and primarily in the sporadic form of the disease, which accounts for 90 percent of affected individuals,” added Sebat. “Understanding such sporadic autism will require different genetic approaches and stepped-up recruitment of families in which only one individual has the disease.”

Sebat and colleagues used new high resolution array technology to detect mutations that were present in a child but not in either parent. They screened genetic material from 264 families drawn, in part, from the Autism Genetic Resource Exchange (AGRE) and the NIMH Center for Collaborative Genetic Studies of Mental Disorders.

They found the spontaneous mutations in 14 of 195 people with autism spectrum disorders compared to two of 196 unaffected individuals. Among the 14 autism patients with mutations, 12 were the only affected members of their family, while two were in families with other affected individuals.

Since the rate of mutations was much lower in families with more than one affected member, the researchers propose that “two different genetic mechanisms contribute to risk: spontaneous mutation and inheritance, with the latter being more frequent in families that have multiple affected children.”

The two mutations detected in 196 healthy controls were duplications, while 12 of those in people with autism were deletions of genetic material. Relatively more females had the mutations, suggesting that the anomalies may contribute to disease more equally across the sexes than other causes of autism. Boys with autism outnumber girls 4 to 1.

Since each mutation is individually rare — few were seen more than once — the results suggest that many different sites in the genome likely contribute to autism. “Failure to develop social skills and repetitive and obsessive behavior may in fact be the consequence of a reaction to many different cognitive impairments,” note the researchers.

The new study is part of a growing body of NIH-funded research on autism genetics. For example, researchers last fall reported discovery of a gene version linked to autism and how it likely works at the molecular level to increase risk. The new study was also supported by the Simons Foundation, Autism Speaks, Cure Autism Now, Southwestern Autism Research and Resource Center, NAAR, Tampere University Hospital Medical Fund.

Talking to Pediatrician About Autism

Bringing your concerns about your child's development to the attention of your pediatrician can be difficult for many parents. It can be even more difficult to be persistent if your pediatrician tells you not to worry, or doesn't take your concerns seriously. Here are some tips to help you make your concerns clear to your pediatrician, and steps to take if you're not satisfied with his or her response to your concerns.

Be prepared with a list of concerns

Before your visit with your pediatrician, sit down with a checklist of developmental milestones that are appropriate for your child's age. Go through the list and check off the ones that concern you.

Be specific
It will be far easier for your doctor to grasp the situation if you say, "She doesn't turn her head to look at me when I call her name" than if you say, "I think there's something wrong with her hearing". Try to be as specific as you can about all of your concerns. Remember that your doctor only sees your child for about 15 minutes during a very busy day. Your observations and reports are a major factor in shaping his opinion.

Avoid comparisons with other children
When you say 'My neighbor's one year old is doing this, but my child isn't yet', your doctor may go into 'soothing' mode. Rather than address your concern, he may address what he sees as 'nervous mother syndrome'. Stick to descriptions of your child's behavior without referencing other children.

Insist on a routine developmental screening
Routine developmental screenings only take a few minutes - and your doctor may actually be doing one without you being aware of it. You may have filled out a questionnaire about your child's behavior that asks questions like 'Does your child smile at you?' and 'Is your child using 2-word sentences?' or your doctor or nurse may ask those questions. If you're not sure that your doctor has done one, ask. If he hasn't, ask him to do so.

Be persistent
If your doctor doesn't seem to take your concerns seriously, or refuses to perform a simple developmental screening, ask him to explain why. Don't be afraid to ask for a referral to another doctor, or to schedule a follow-up appointment to discuss your concerns specifically.

Ask questions
Part of your doctor's job is to make sure that you understand any diagnoses or the results of any tests. If you don't understand a term that was used, ask your doctor to define it or give you examples. If he gives you the results of a test, ask him what they mean if you're not sure.

If your doctor refuses to refer your child...
Know your rights. In many states, you don't need a doctor's referral to have your child evaluated for Early Intervention needs. In Massachusetts, for instance, any parent can contact their local school department or health department to ask for an Early Intervention screening. You'll find contacts and information about Early Intervention at the (http://www.nectas.unc.edu/) National Early Childhood Technical Assistance web site.

Keep in mind that you are the person who knows your child best, and who is with him or her more than anyone else in the world. If you have concerns, it's far better to bring them up and have them addressed appropriately than to wonder - or worse, put off a diagnosis and waste precious time that could make a world of difference to your child.

At the same time, the American Autism Society cautions that autism is a broad diagnosis that encompasses an almost infinite combination of symptoms, abilities and levels of abilities. Every child diagnosed with an autistic spectrum disorder is an individual with individual needs. This is echoed by many other specialists and experts in the field of autism who believe that each child with autism must have an individualized treatment plan that addresses their particular needs.

The Importance of Autism Diagnosis

Getting an accurate diagnosis is important in getting appropriate treatment for your child. Without an official diagnosis, your child is in limbo, legally and financially. With a diagnosis, doors to treatment open that are locked as long as doctors are 'being nice' to you.

I am not suggesting by any means that you push for a diagnosis that isn't certain. No parent wants their child to be diagnosed with a lifelong disorder that will affect everything that they do. There is a tendency, however, among doctors to cushion the blow. Since there are no definitive tests for autism, diagnosis is as much art as science, and doctors would rather not have to tell you that your child is autistic. They may couch it in other terms - your child 'meets the criteria for autism' or 'displays autistic tendencies'. Many will tell you bluntly that they don't want to label your child, because labels have a tendency to stick for life, and if they're wrong, your child may never be given a proper chance. While their concerns are commendable, the truth is that it is far easier to reverse a diagnosis than it is to get one in the first place.

Those doctors fail to take a number of things into account, among them the toll that uncertainty takes. Not having an official diagnosis leaves you in limbo - you know that there's something wrong, but you can't put a name to it. You can't effectively advocate for services for your child from the school department or from other sources without an official diagnosis. Insurance won't pay for certain treatments or special schools that may help your child learn despite his disability unless there's an official diagnosis.

Getting appropriate treatment for your child depends on having an accurate diagnosis. If your doctor is reluctant to give you an official diagnosis, ask him why. Don't be afraid to ask for a referral to a specialist, or to a team for diagnosis. If, in the end the verdict is that your child does NOT have an autism spectrum disorder, thank whatever Powers you believe in, and move on, enjoying your slightly quirky, eccentric child. If, on the other hand, the doctors and specialists agree on a diagnosis of autism, you now have a tool that will help ensure your child the treatment that he needs.

Secretin To Treat Autism Controversy

One of the currently controversial treatments for autism is the use of the neurotransmitter secretin. It was used to test pencreatic function in which capacity, amongst other things, it stimulated the pancreas to produce peptidase enzymes. According to one of the theories for the causation of autism ( the "opioid excess theory") substances with morphine like activity (peptides) can be derived from incomplete digestion of certain food, in particular casein, from milk and dairy produce, and gluten from wheat and some other cereals. These peptides can reach the brain and result in the range of symptoms which constitute autism. The peptidase enzymes resulting from the use of secretin will increase the breakdown of these substances and this will result in improvements in the symptoms of autism

The secretin used in the earliest studies, (from Ferrings) and in some of the current studies (Secrepan and Gaspretin) are derived from pigs and it would, therefore, differ slightly from the human product. Fears were raised that the foreign nature of the secretin could result in the production of antibodies to the secretin from the subject or following infusion but there is little evidence, to date, that this is, in fact, of clinical significance. A synthetic (pig) product, (Secrelux), is now available and is probably considerably purer than the pig derived material. It will be some time, probably over a year, before the biotechnologically derived variety, very pure and fully tested, appears on the market (assuming it satisfies the regulatory authorities).

So how did a protein that's used by the body in the digestive process end up being touted as an effective treatment for autism?

First, you need to know that many children with disorders in the autism spectrum also have digestive and intestinal disorders, and research has shown that a lot of those have deficiencies of secretin and other proteins used in digestion. In 1998, doctors from Maryland published an article in the Journal of the Association for Academic Minority Physicians about three children with autistic spectrum disorders. Within five weeks of receiving intravenous infusions of secretin to help regulate their digestion, all three showed "a dramatic improvement in their behavior, manifested by improved eye contact, alertness, and expansion of expressive language."

The intestinal hormone secretin, considered by some to be a promising drug in the treatment of autism, does not improve the symptoms and should not be used to treat the disorder, according to a new review of studies.

By October of 1998, the National Institutes of Health had posted their position on the use of secretin to treat autism - which essentially said that it does not have an official position. Specifically, the letter states that any use other than for gastro-intestinal treatment is considered an 'off-label' use, for which there have been no safety or efficacy (effectiveness) studies.

It goes on to state, however, that there has been one small safety study that seems to suggest that a single dose treatment of secretin is safe, in that it has no unwanted side effects, and invites researchers to submit applications for funding research.

That wasn't the last word, however. All over the country, parents of children with autism spectrum disorders are still reporting significant improvements in speech, behavior and attention in children who are given secretin. Because so little is know about the causes of autism, there is a possibility that there is a specific sub-group of children with autism who may benefit from the use of secretin. Currently, it is not a recommended treatment for autism in general. Those who advocate its use suggest that it be used in the specific sub-group of children who might benefit from its approved use - to treat gastrointestinal disorder.

In recent months, some politicians and patients have also suggested that a mercury compound called thimerosal, formerly used as a preservative in vaccines, may be one of the culprits behind autism. Although the purported connection has been well publicized, the Institute of Medicine concluded earlier this year that there is no evidence of a link between vaccines and autism.

Autistic disorders are probably caused by a combination of genetic, environmental and brain development factors. Unfortunately, there is still much ignorance about the safety and usefulness of secretin and it is to be hoped that the mists will clear soon. The serious side-effects prophesied in some quarters have not materialised but, at the same time, the benefits have been less spectacular than the early reports in the press and on television had led us to expect. In the meantime, parents and physicians must make their own choices based upon limited knowledge and understanding. It is to be hoped and anticipated that this situation will improve over the coming months.

Even if it eventually transpires that there are only a few who will benefit from the use of secretin, it will have been worthwhile. The secretin story has also caused many researchers to focus on the body as a whole and to treat the person with autism holistically rather then to concentrate solely on the perceived behavioural and psychological abnormalities.

Autism is not always about disabilities

Autism is not always about disabilities. In fact, many of autistic people have extremely extraordinary abilities and talents compared to normal people. Stephen Wiltshire, for example, can make some amazingly detailed drawings of cities.

Watch Video
Are you capable of multiplying 147,631,789 by 23,674 in your head, instantly? Physicist Allan Snyder says you probably can, based on his new theory about the origin of the extraordinary skills of autistic savants

Despite many autistic people are regarded as someone who live in their own world and unable to correctly express their emotions, Jerry Newport and Mary Newport proved that Aspie person can also fall in love. Mozart and the Whale is a film based on this true Asperger’s Love Story.

Autism and Deafness

Two instances that impair this free communication and dialog between people are autism and deafness. These two are often confused with the other. Autism may be misdiagnosed as deafness and vice versa. Sometimes though, a child can actually turn out to be both autistic and deaf.

Autism

Autistic children are regarded as children who live in their own world. The condition displays lack of proper communication skills and repetitive behavioral patterns. Some may think that they are stuck to being such but actually these children are capable of observing and learning too, only in their own way. There is a need for the people around the kid, the family, to understand the world of the child.

Deafness

This condition manifests in the inability of a person to hear and understand speech. The problem may stem from birth defects or diseases like ear infections. As a result of the disability, the child will have a difficulty of learning to speak and comprehend.

Autism and Deafness

The lack of capability to communicate and relate in both cases actually poses the difficulty of diagnosing the condition. They often get mixed up! Most parents might think that the unresponsiveness of their kids are due to hearing defects.

It was found by recent studies that 30% to 50% of autistic people turn out to be deaf too. There could actually be more out there, we just happen to treat them as one that we ignore already the symptoms that point to the other condition.

What basically are the differences?

Deafness may be fixed by operation or hearing aids, while autism can not be. Autism will have to be addressed properly to give way to a brighter future to the child.

Deaf kids can still comprehend through their eyes. They can perceive through their sight, the only problem is that they can't hear. An autistic child on the other hand may actually be able to see and hear, but they act like they are deaf because they do not respond. They simply cannot respond.

Kids with hearing disorder can still express themselves in many ways. They can watch other people. They can signify their feelings through gestures. They sometimes are able to make sounds if they are happy or if they are hurt. An autistic child may not be able to do this.

Address the situation properly. Instead of ignoring the symptoms and delaying the confrontation of the dilemma at hand, the situation of the child should be prioritized.

Seek for the help and assistance of experts. Once you saw the symptoms, do consult the experts right away, whether you suspect it as deafness or autism or both.

Send your child to special institutions. There are many institutions out there that cater to providing special education to autistic and deaf children. Make sure also that you yourself are able to attend seminars and consultations so you will understand better the situation.

Maintain a support group that will constantly give you strength and courage when things get rough. There are known associations and committees that actually help parents and family members of children who are both deaf and autistic.

Dealing with deafness and autism may really pose great challenges to the family. There may be pains and frustrations as your child struggle to express, to communicate or to learn. What matters though is that you are there as someone who will listen, someone who will reciprocate and someone who will affirm.

Early Symptoms of Autism

According to NIMH, although there are many concerns about labeling a young child with an ASD, the earlier the diagnosis of ASD is made, the earlier needed interventions can begin. Evidence over the last 15 years indicates that intensive early intervention in optimal educational settings for at least 2 years during the preschool years results in improved outcomes in most young children with ASD.

So right now we are going to discuss what to look for as early symptoms of autism.

The Childhood Autism

Autism is, generally, a pervasive development disorder or better known as PDD, that manifests delayed development in basic communication skills.

This general symptom of childhood autism is not clearly diagnosed until about the child is already on his or her toddler or pre-school stage.

In its entirety, autism, which is mostly prevalent in children, is characterized by the child's inability to communicate verbally or to emotionally bond with other people.

The diagnosis of such disorders through these general symptoms may be too late if the physician or the parents will only depend on these latent indicators.

Hence, it is important to detect the early symptoms of autism to initiate immediate observation, effective therapy, and protective measures, if necessary.

The Early Signs and Symptoms

Any suggestion that the patient is suffering from certain disorders such as autism should be put on the expert's guard at once. Abnormalities in whatever area of development as well as any signs of metabolic disorder should be immediately detected and diagnosed.

For some people, it is difficult to identify the probable symptoms of childhood autism. Usually, they confuse the child's behavioral problems as something that they thought they are the ones who were at fault. This is, indeed, a wrong connotation because autism is not caused by environmental factors. In fact, no one knows what the exact causes of autism are.

However, the early diagnosis of the disorder is very vital in helping the child minimize the aberrations. Treatments and therapies will be infused immediately whenever the problems are detected on its earliest stage.

Therefore, for people who want to know the initial symptoms of autism, here are some of the basic indicators that can be associated with infants as young as 1 year old.

1. Be wary if your child is not able to manifest normal gestures such as pointing or waving by the time he turns one year old.

Normally, children should be adept in more gestures that show proper body and brain coordination such as waving bye-bye or pointing to certain objects that fascinates them by the time that they turn one.

If, in any case, your child does not manifest gestures such as those mentioned, then, your child is most likely a candidate for autism.

2. No chatting or coos by 12 months of age.

This would mean that your child is having delayed communication developments, which is the primary indicator of childhood autism.

3. By the time your child reaches 16 months and still he cannot utter even a single word, then, he may be having difficulty with verbal communication, which is one of the vital signs in autism.

4. When children reach 24 months and still, they do not utter two-word phrases on their own and keep on repeating what other people are saying could mean early signs of autism.

5. Your child may be autistic if he or she had lost communication or social skills.

These early symptoms are very important in identifying the probability that the child is autistic. Thus, parents and the people around them should be aware that these signs are not normal and could be good indicators of autism.

Keep in mind that the consequences of neglect in reporting or failure to realize the true gravity of the situation may be serious. By the time people realize the matter, it may be too late already.

For further information regarding early symptoms of autism please go to NIMH homepage.