The Genealogical Study of Autism Lanruth L. Tambogon, Mary Anne B. Garduque, Mikaella G. Santos, Ruby Ann D. Aurelio, Jerahmae B. Ugot, and Jane Angelle Mae P. Agulo

Manila Central University, October, 2014

ABSTRACT Autism is a developmental disability, usually showing up in children before age three. Autism interferes with the way a child interacts the world. It affects the way a child communicates, in both verbal and nonverbal ways, it affects social interaction, both physically and verbally, and lastly, it can cause a person to repeat behaviors or words. The aim of this study is to know and identify the origin of autism in a family, and who among the parents have the big contributions to the passing of the genes that carry autism, and how the external factors affect the development of this disorder. This study was conducted at Zion Christian Center, and three (3) families with cases of autism participated in this study. Through interviewing and Pedigree analysis the researchers were able to determine the genealogy of autism. The findings revealed that male are at greater risk for developmental disorders, such as autism, than females. Recommendations for parental styling for children with autism are thoroughly discussed in this study as well.

Keywords: Autism, Pedigree Analysis, Inheritance, Multifactorial disorder, Genetics of Autism

Introduction

Autism has been mystifying scientists for more than half a century. The complex behavioral disorder encompasses a wide variety of symptoms, most of which usually appear before a child turns three. Children with autism are unable to interpret the emotional states of others, failing to recognize anger, sorrow or manipulative intent. Their language skills are often limited, and they find it difficult to initiate or sustain conversations. They also frequently exhibit an intense preoccupation with a single subject, activity or gesture. (Rodier, 2000). In fact, autism is sometimes described as “mind

blindness.” Yet the condition is more than a disability. Autistic people excel at a certain tasks (Cowley, 2000).

According to Nash (2002), autism was first described in 1943 by Johns Hopkins psychiatrist Leo Kanner, and again in 1944 by Austrian pediatrician Hans Asperger. Kanner applied the term to children who were socially withdrawn and preoccupied with routine, which struggled to acquire spoken language yet often possessed intellectual gifts that ruled out a diagnosis of mental retardation. Asperger applied the term to children who were socially maladroit, developed bizarre obsessions and yet were highly verbal and seemingly quite bright. There was a striking tendency, Asperger noted, for the disorder to run in families, sometimes passing directly from father to son. Clues that genes might be central to autism appeared in Kanner’s work as well.

Rodier (2000) stated that, at least 16 of every 10,000 babies are born with autism or one of its related disorders. Since autism was first identified in 1943, scientists have made great strides in describing its symptoms. The biological basis for autism, however has been elusive­an unfortunate circumstance, because such an understanding could enable researchers to identify the leading risk factors for autism and possibly to design new treatments for the condition. By examining the inheritance of the disorder, researchers have shown that autism runs in families, though not in a clear­cut way. Siblings of people with autism have a 3 to 8 percent chance of being diagnosed with the same disorder. The results fit best with models in which variants of several genes contribute to the outcome. To complicate matters further, relatives of people with autismmay fail to meet all the criteria for the disorder but still have some of its symptoms. Although these relatives may have some of the gene variants linked to autism­whatever they may be­for some reason the genetic factors are not fully expressed in these individuals.

Perhaps the most provocative finding scientists have made to date is that the components of autism, far more than autism itself, tend to run in families. Thus, even though profoundly autistic people rarely have children, researchers often find that a close relative is affected by some aspect of the disorder. A sister might engage in odd repetitive behavior or be excessively shy; a brother might have difficulties with language or be socially inept to a noticeable degree (Nash, 2002).

Roughly 5 percent of kids with autistic siblings have autistic disorders themselves. And the risk of autism is 75 percent among people with affected identical twins. Researchers are studying “hot spots” on several chromosomes that could harbor culpable genes, but none of those regions has been linked consistently to the disorder (Cowley, 2000). The twin study of Hallmayer et al in 2011 increased the evidence for a role of shared environmental factors in addition to genetic heritability in the etiology of autism (Beaudet, 2012).

Lovaas (1987), who first used ABA for children with autism in the early 70s. His groundbreaking research documented the effectiveness of using intensive ABA in these children. After 2 years of treatment, 48% who received intensive ABA intervention have obtained the best learning outcome and made average IQ gains of 30 points. A research group at University of Nottingham Malaysia is using state­of­the­art facilities in their neuroscience laboratories for research into autism. In partnership with the National Autism Society of Malaysia, Global Priority Group: Biomedical Imaging

is developing a system for early diagnosis of autism using eye movement recording technology and electroencephalogram (EEG). The group is also undertaking a study to establish a systematic approach to diagnosis. To date, there is a serious lack of knowledge and expertise in diagnosis in Malaysia, and internationally recognized testing instruments are not widely available. The epidemiological study will allow an estimate of the proportion of people who suffer with autism in a large scale programmed of diagnosis. The work will provide a vital opportunity for clinicians and researchers in Malaysia to build up capacity in clinical testing and epidemiology. It will also benefit families in Malaysia who are coping with children with developmental disorder.

In the study of Dr. Alexis L. Reyes, former president of the Philippine Society for Developmental and Behavioral Pediatrics, as well as, the Associate Professor of the Developmental Pediatrics department at the University of the Philippines, included mostly males and only fifteen percent of the participants were females. Dr. Reyes discovered that there is not a substantial amount of data regarding the prevalence of people with autism. The number of cases reported still does not paint an accurate picture of the population who are on the autism spectrum. This, she says is because it is still not being diagnosed. It is usually the parents who bring the issue to the attention of the doctors (Alvarez, 2012).

The influx of autism case in the Philippines opened many advocacies for person with learning disabilities, and autism is one of the largest numbers of case that Special Education has. Its causes are still a question for many, and researchers are still racing to identify the genes linked to autism; this disorder also affects four times as many boys as girls.

Thus, the present study endeavored to determine the cause of autism, and to know who among the parents can greatly contribute to the inheritance of this disorder by examining three families who have an autistic child. Understanding and identifying the origin of autism may provide everyone enough knowledge about the disorder and can help to prevent the occurrence of autism.

Methodology

This study aims to examine the origin of autism in a family. Three families with a child

that has autism and are currently enrolled at Zion Christian Center were the respondents of this study. The parents of each child were asked about the background of their families, especially in any developmental disorder. Using pedigree analysis the possible contributor of the disorder was examined, starting from the grandparents of the affected individuals, to their parents, and to them.

Results and Discussion

Figure 1.1. Pedigree Chart of Family X

Figure 1 shows the pedigree chart of family X in which there are two descendants from the father side who have autism, and they are both males.

Figure 1.2. Pedigree Chart of Family Y

Figure 2 shows the pedigree chart of family Y, in which the two males from the third generation from the mother side have autism.

Figure 1.3. Pedigree Chart of Family Z

Figure 3 shows that the son is the only affected individual in the third generation of the two families.

80 percent of autistic people are males, meaning the risk is five times greater for boys

(Cowley, 2000). Based to the results that have gathered, the affected individuals in these three families are all boys, and there are all only child. In the article of Berthiaume (2014), she stated that Autism does tend to run in families. Autistic children often have autistic siblings, especially if they are twins. In fact, if a family has one autistic child, there is a one­in­five chance that their next child will have autism too. Because autism tends to run in families, there is likely a genetic component to the disorder. However, the exact way in which the genetic component of autism operates is not known. Like many hereditary conditions, your genes give you certain likelihood that you will have autism. Other factors like the environment also play a role in deciding which individuals develop autism.And that may be the reason why families who have an autistic child tend to have an only child, because they are afraid that their next child might have the same disorder too. Meanwhile, in a sibling study made by Zhao et al. (2007) looked at a database containing pedigrees of 86 families with two or more autistic children and found that 42 of the third­born male children showed autistic symptoms, suggesting that parents had a 50% chance of passing on a mutation to their offspring. The mathematical models suggest that about 50% of autistic cases are caused by spontaneous mutations. The simplest model was to divide parents into two risk classes depending on whether the parent carries a pre­existing mutation that causes autism; it suggested that about a quarter of autistic children have inherited a copy number variation from their parents. There is strong evidence to suggest that there are more boys with ASDs (autism spectrum disorders) than girls. Brugha (2009) surveyed adults living in households throughout England, and found that 1.8% of males surveyed had an ASD, compared to 0.2% of females. Experts do not know what causes autism, but it affects about one in 500 persons. Boys are three to four times more likely to develop autism than are girls. Hereditary appears to play an important role in autism. A family that has one child with autism has a five to 10 percent chance that another child will also develop autism. Research also has found that there is no link between any vaccine or combination of vaccines and autism.

In so many ways, study after study has found that autistic people do not parse information as others do. University of Illinois psychologist John Sweeney, for example has found that activity in the prefrontal and parietal cortex is far below normal in autistic adults asked to perform a simple task involving spatial memory. These areas of the brain, he notes, are essential to planning and problem solving, and among their jobs is keeping a dynamically changing spatial map in a cache of working memory. As Sweeney sees it, the poor performance of his autistic subjects in the task he set for them – keeping tabs on the location of a blinking light – suggests that they may have trouble updating that cache or accessing it in real time (Nash, 2002). Scientists are gaining tantalizing insights into the autistic mind, with its odd capacity for genius as well as detachment. And thought the suspected causes range from genetic mutations to viruses and toxic chemicals, people now know it’s a brain­based

developmental disorder ant not a result of poor parenting. David Amaral, a neuroscientist at the University of California, studied the autopsies of autistic people and they have found that cells in the limbic regions that mediate social behavior are often small and densely packed, suggesting their early development was interrupted. And neural­imaging studies are showing differences in how autistic and non­autistic brains respond to social cues, such as faces or eyes (Cowley, 2000).

Autism affects different parts of the brain in females with autism than males with autism. Scientists at the Autism Research Centre at the University of Cambridge used magnetic resonance imaging to examine whether autism affects the brain of males and females in a similar or different way. They found that the anatomy of the brain of someone with autism substantially depends on whether an individual is male or female, with brain areas that were atypical in adult females with autism being similar to areas that differ between typically developing males and females. This was not seen in men with autism. One of their new findings is that females with autism show neuroanatomical masculinization. This may implicate physiological mechanisms that drive sexual dimorphism, such as prenatal sex hormones and sex­linked genetic mechanisms (Baron­Cohen, 2013). Study suggested that Autism affects male and female brains differently.

To complicate matters researchers believe that the gene is probably just one of dozens linked to autism, many of which may trigger the disease only if a genetic predisposition is activated by some external factor. Although our genome have already decoded, our “envirome” – everything that influences a person after conception, from parenting to pollution – remains a fragmented riddle. To decipher the envirome’s role in the disease, William Eaton a psychiatrist at the Bloomberg School of Public Health at Johns Hopkins University, recently helped to conduct a large­scale study involving nearly 700 Danish children. Some intriguing correlations emerged. Scouring for trends among a host of parameters such as birth weight and socioeconomic status, scientists discovered an increased prevalence of autism both in children with a family history of schizophrenia and in those whose births involved complications such as premature and breech delivery (Carnett, 2005).

Conclusion

The three families who participated in this study show that the affected individuals

in their families are the males, and they only have an only child. Autism appears to be more common among boys than girls. This could be because of genetic differences between the sexes, or that the criteria used to diagnose autism are based on the characteristics of male behavior. However, our understanding is far from complete, and this will remain the case until we knowmore about the causes of autism. The aim of this study is to know who the main contributor of the disorder is, still remain unanswered. At present, what exactly causes ASD is still unknown. It is certain that genetics play a large role. However, we do not know what proportion of ASD cases have some inherited susceptibility nor do we know how large a proportion of autism cases are entirely caused by inherited genetic factors. Further, while genetic risk factors are important, this does not rule out a potential major role for non­heritable risk factors. That said, there is little conclusive evidence supporting a prominent role for any particular non­genetic risk factor. However, part of the reason why no other risk factors have been identified may be that genetic and non­genetic factors need to be studied together in order to get a clear picture. In other words, only when studying ASD cases with a certain genetic background may we be able to see that a particular non­genetic trigger was important. Further study is needed to answer who among the parents have the largest role in the development of autism.

Autism, as a multifactorial disorder, shows that it is not solely the genes that cause it; external factors also are responsible for the growing numbers of the disorder. If autism indeed caused by complex interaction of genetic and external factors, Pessah believes that eliminating the environmental problems would be easier in the short term than the awesome biomolecular challenge of finding and altering the offending DNA (Carnett, 2005).

There is no known cure for autism. However, early behavioral­based interventions can help children to better develop the communication and social skills needed to improve their functional abilities. Although a number of different specific behavioral and educational techniques are currently used as part of interventions for individual children with autism, these techniques are grounded in a vast body of research based on a common set of behavioral and learning principles. Early intervention programs generally emphasize attending to social stimuli, imitation skills, language comprehension and usage, appropriate play skills, and social interaction. For certain subgroups of children with ASD, drug therapy may be available that reduce problematic behaviors. However, of the numerous other interventions that have been proposed over the years, none have been proven effective.

Nothing will make the search for autism’s causes simple. But every risk factor that we are able to identify takes away some of the mystery. More important, new data spawn new hypotheses. For

parents who have children that have autism, doctors recommend that at least one parent stay at home to take care of the child with condition. For the replication of this study, the age and gender must be added to the variable to be studied, and a larger number of participants must be used, lastly, at least five generation of each family must be studied in the pedigree analysis of the disorder to attain the aim of the study.

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