AUTISM SPEAKS SAYS 1CHILD IS DIAGNOSED EVERY 20 MINUTES WITH AUTISM, WE CAN STOP THAT NOW BY OURSELVES

WHY NOT RENAME CHILDHOOD SCHIZOPHRENIA AS AUTISM AND MAKE A FINANCIAL KILLING ON IT AND NEVER TELL THE PUBLIC THAT FATHERING BABIES IN YOUR MID 20s TO VERY EARLY 30s WOULD PREVENT A GREAT DEAL OF PATERNAL AGE AUTISM/CHILDHOOD SCHIZOPHRENIA?

DON'T WALK FOR AUTISM, PASS THE WORD ABOUT THE RIGHT TIME TO FATHER BABIES, AND THE CONNECTION TO A FAMILY HISTORY OF AUTOIMMUNE DISORDERS AND IF THE MOTHER'S FATHER WAS OLDER WHEN SHE WAS BORN
WE CAN LESSEN THE EPIDEMIC AND NOT WASTE OUR MONEY. HAVE THESE CHARITIES STOPPED DUCHENNE'S NO! DIABETES NO! ALL JERRY LEWIS NEEDED TO SAY WAS TO FATHER YOUR BABIES BY 33 AND THERE WOULD BE LESS AUTISM AND DIABETES AND DUCHENNES. SCIENTIFIC RESEARCH ON AUTISM IS A SCAM- AUTISM IS NOT UNKNOWN AND BEFORE 1994 IT WAS A TERM THAT WAS VERY SPECIFIC TO A VERY WELL-DEFINED GROUP OF SYMPTOMS. SINCE 1994 EARLY CHILDHOOD SCHIZOPHRENIA IS DIAGNOSED AS AUTISM---THIS IS CAUSED BY OLDER FATHERS SPERM MAKING CELLS MUTATING ---THIS HAS BEEN OBSERVED SINCE 1958 AND SINCE 2001 MANY STUDIES FROM ALL AROUND THE WORLD HAVE CONFIRMED OLDER DAD AS A ROBUST CAUSAL FACTOR. OLDER DAD PAST 33 = MORE AUTISM GUARANTEED--REMEMBER VIRGINIA TECH AND YOU SEE AUTISM

Pittsburgh AUTISM SPEAKS "Walk Now for Autism"
The Pittsburgh AUTISM SPEAKS "Walk Now for Autism"


Thousands of individuals, families and friends whose lives are impacted by autism will join together to raise much-needed funds for critical scientific research and to increase awareness about a growing health crisis that now affects 1 in every 150 children at the 8th Annual Pittsburgh AUTISM SPEAKS “Walk Now for Autism” on Saturday, June 2, 2007 at Heinz Field.


Joining the walkers at this year’s event, sponsored by Toys “R” Us, will be special guests Larry Richert from KDKA News Radio 1020; Jake Ploeger, Channel 4 Action News Anchor and Mark Roithmayr, President of Autism Speaks.



Autism is a complex brain disorder that inhibits a person’s ability to communicate and develop social relationships, and is often accompanied by extreme behavioral challenges. One in 150 children is now diagnosed with an autism spectrum disorder, including one in 104 boys. Another child is diagnosed every 20 minutes.




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This newspaper is running this story over again to let people know!


ReutersIST(13/1/2007)


Chicago, September 04, 2006
First Published: 00:00



Children fathered by men at age 40 and older have a higher risk of developing autism, possibly because of mutations or other genetic changes, researchers reported on Monday.
The study "provides the first convincing evidence that advanced paternal age is a risk factor for autism spectrum disorder," said the authors from Mount Sinai School of Medicine, New York, and the Institute of Psychiatry, King's College London.

The findings were based on a look at thousands of children born in Israel during the 1980s. All males and three-fourths of the females born in the time period involved were checked by Israeli draft officials at age 17 and any psychiatric disorders were recorded.

"Offspring of men 40 years or older were 5.75 times more likely to have (autism disorders) compared with offspring of men younger than 30 years," said the study published in the Archives of General Psychiatry.

"Advancing maternal age showed no association," it added.

Autism can cause symptoms ranging from social isolation to repetitive and damaging behaviour and sometimes mental retardation.

The problem has become increasingly common, affecting 50 in every 10,000 children in the United States, in part due to greater awareness and changes in diagnoses, the study said.

The report said several genetic mechanisms might be behind the paternal age association found, including spontaneous mutations in sperm-producing cells.

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GIVE MONEY TO AUTISM, BUT NOT GIVE MONEY TO A PUBLIC HEALTH WARNING THAT OLDER FATHERING OF BABIES AND AUTISM GO HAND AND HAND- THAT COULD ACTUALLY HELP PREVENT SOME PATERNAL AGE DERIVED AUTISM WHICH IS THE CAUSE OF A CONSIDERABLE PORTION OF THE TOTAL

Philanthropy 2006

James. H. Simons

Amount Given or Pledged 2002-2006: $257 million
Causes: Math and science education, autism

Twenty-five years ago, top mathematician James H. Simons left a career in academia to start New York-based investment firm Renaissance Technologies. The 68-year-old money manager is now one of the richest men in the U.S.—and is fast becoming one of the nation’s top philanthropists. A former Harvard and MIT professor whose hedge fund thrives on algorithms and computers, Simons supports math and science initiatives in New York City, including his nonprofit, Math for America, and Stony Brook University, where he headed the math department for eight years. His private family foundation has assets worth half a billion dollars. In February, he committed $100 million to a study on autism, a disorder that affects his daughter. Since losing two adult sons in separate accidents 10 and three years ago, the family has maintained a 130-acre nature preserve on Long Island and built hospitals in Nepal in their memory.





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From Pharmalot


There’s nothing like a convention. And more than 15,000 doctors visited Washington, D.C. last week to attend Digestive Disease Week, the largest-ever gathering of gastrointestinal physicians. So Integrity in Science Watch paid a visit. Here’s the report.........................


The quietest space on the convention floor was the corner reserved for the small booths of patient advocacy groups, text book sellers, and scientific journals. ‘We don’t get any sponsorship from corporations for our meeting booths,’ says Crohn’s & Colitis Foundation of America rep Laura Hitchens, eyeing the towering Fuji stereo sound system blaring a description of a colonoscopy camera.

Thelma King Thiel of the Hepatitis Foundation says they wouldn’t say no if a company was to offer to fund their booths but, she adds, not many companies are interested in prevention.

------------------------------------------------------------------------------------

I WONDER WHAT THE AMERICAN MEDICAL ASSOCIATION'S VIEW IS ON WARNING THE PUBLIC THAT THERE IS A MALE BIOLOGICAL CLOCK AND THAT ADVANCING PATERNAL AGE AND AUTISM ETC. ARE CLOSELY RELATED. OF COURSE FERTILITY DOCS WOULD NOT SUPPORT THAT NEWS NOR WOULD MOST DOCS TREATING THE CHRONIC DISEASES WHICH WOULD NOT EXIST IN SUCH GREAT NUMBERS IF MEN KNEW TO FATHER THEIR BABIES IN THEIR MID 20S TO 32,33


ON THE AMA ON SERMO FROM PHARMALOT

The partnership was struck with a company called Sermo, which wants to use a web site to tap into the collective wisdom of its growing network of 15,000 U.S. docs. The two-year deal allows the AMA to survey its members on hot topics, just as Sermo’s Wall Street subscribers solicit docs’ opinions to help guide trading decisions on drug and device stocks.

But some docs are skeptical the service can advance medical safety, and PhRMA frets the service will spread as much rumor as fact. The AMA, however, hopes the deal will open a new line of communication, allowing its 250,000 docs to share everything from advice about treating a patient’s unique symptoms to opinions on whether the FDA should approve an experimental drug.

This does sound like a win-win, but there are potential problems. If creating an online community is so important, the AMA should do so. The organization shouldn’t, however, be in the business of promoting a forum - which allows anonymous postings - in hopes of enticing Wall Street firms willing to pay $100,000 to $500,000 for an online tip sheet.

This isn’t really about serving public health. This is exploiting the AMA membership in a way that cynically values the info exchanged as a high-priced commodity to be used to bolster the AMA’s bottom line. Exchanging medical info is laudable, but peddling the info in a way that may result in manipulation doesn’t build credibility.


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MORE AUTISM, CEREBRAL PALSY MENTAL RETARDATION IN IVF KIDS PATERNAL AGE IS A MAJOR RISK FACTOR FOR ALL OF THE ABOVE
Children born after IVF treatment 'face higher health risks'

Ian Sample in New Orleans
Thursday October 26, 2006
The Guardian


Children born to couples who have undergone fertility treatment are more likely to be diagnosed with autism, cancer and other disorders such as cerebral palsy and mental retardation, researchers claimed yesterday.
The higher risk to child health is believed to be caused by medical problems in the parents, such as diabetes and hypertension, damaging the child in the womb, but doctors conducting the study said IVF and other fertility treatments may also play a role. Medical records of children born after their parents sought fertility treatment showed they were four times more likely to have autism than those born to fertile parents. Childhood cancers including leukaemia and brain tumours also rose.

The risk of more minor problems, such as attention deficit hyperactivity disorder, rose by 40%, and other medical conditions affecting hearing and sight nearly doubled. Children had a 30% higher chance of being admitted to neonatal intensive care units and to stay in hospital for more than three days if they were born following fertility treatment, the study found.

The researchers stressed the figures represent relative risks. In July researchers at Guy's and St Thomas' hospital in London reported the prevalence of autism to be 0.39% in the general population, a figure that will include some children born to parents aided by fertility treatment. A fourfold rise in the risk of autism would see a child's chances of having the condition increase to 1.56%.

I have two children with the disorder. NO ONE else in either of my or my husbands family has autism.

"Type 1 diabetes is an autoimmunity issue and its not related to lifestyle. I wouldn't be suprised if it is linked with autism however considering I have a child with both. Our family history is all Type 2 diabetes, my child is the first to be Type 1. I seem to see more and more kids with Autism though that have secondary health concerns like diabetes, allergies, etc. Perhaps Autism itself is the result of an autoimmune response. I don't think there is enough evidence in any direction to say what the root cause of Autism is or how it is related to other disorders. I wish there were because I would be first in line to hear the news.
There also is not enough evidence to support the rationale that the increase in autism statistics is only due to increased diagnosics. There IS however evidence showing that there is a genetic predisposition to Autism with and Environmental trigger. I happen to believe it is on the rise. I have two children with the disorder. NO ONE else in either of my or my husbands family has autism."

In a Man Treated for Cancer there was increased and persistant DNA damage in sperm, the Institution of Better Surveillance of Genetic Disease in

Offspring of men surviving cytotoxic therapies may provide more robust risk assessment.


1: Int J Androl. 2002 Oct;25(5):255-61. Links
Sperm DNA damage and cancer treatment.Morris ID.
School of Biological Sciences, University of Manchester, Manchester, UK. i.morris@man.ac.uk

Cancer treatments are well known to adversely affect male fertility. Reduction of sperm output arises from the cytotoxic effects of chemo- or radiotherapy upon the spermatogenic epithelium. However, if the epithelium survives there is a hazard to reproduction as the treatments are also mutagenic. The presence of DNA damage in the male genome is shown in animal experiments where there is transgenerational expression as a variety of effects ranging from miscarriage to carcinogenesis. The application of DNA damage methodology to sperm provides the opportunity for direct assessment. The Comet and Chromatin structure assays (SCSA) measure DNA damage by different principles, however, conclusions arising from the data are similar. DNA damage is present in sperm from fertile and infertile men and there is some association with infertility. Both assays detect sperm DNA damage after in vivo treatment with genotoxic agents. In a man treated with chemotherapy for cancer there was increased and persistent DNA damage in sperm. This information is consistent with the generation of human genetic diseases after conception with sperm carrying high loads of DNA damage. Whilst studies have not supported any association between paternal cytotoxic cancer therapy and genetic disease in their children, it would be unwise to discount these observations. The institution of better surveillance of genetic disease in the offspring of men surviving cytotoxic therapies may provide more robust risk assessment.

PMID: 12270021 [PubMed - indexed for MEDLINE]

This is so disturbing and no one mentions that it is the 63 year old father's sperm that are going to give these boys troubles

IN THEIR FAVOR IS THAT THEY WEREN'T DAUGHTERS WHO WOULD BE AT A MUCH INCREASED RATE FOR SCHIZOPHRENIA DUE TO MUTATIONS THAT ACCUMULATE WITH A FATHER'S AGE ON THE VERY VULNERABLE X CHROMOSOME




NO ONE SPEAKS OF THE HIGH CHANCE THESE BOYS HAVE OF TYPE 1 DIABETES, AUTISM OF SOME TYPE, SCHIZOPHRENIA, PROSTATE CANCER, ALZHEIMER'S, AND MANY OTHER PATERNAL AGE DERVIDED GENETIC DISORDERS. WHICH BEGIN TO SHOW UP IN CHILDREN WHEN FATHERS ARE THE RIPE OLD AGE OF 35. MAYBE MR. BIRNBAUM IS SUPERMAN AND HIS SIX YEAR OLD IS FINE, BUT MAYBE NOT.

FOR INFORMATION ON THE DISORDERS THAT INCREASE WITH INCREASING PATERNAL AGE THAT HAVE ACTUALLY BEEN STUDIED AND ARE NOT OBVIOUS AT BIRTH


Single gene disorders that start rising in offspring in ones mid 30s


Doctors at crossroads with birth of US twins

May 25 2007 at 03:35PM

By Di Caelers


...........................................................................


'Immoral as well as dangerous to the health of mother and child'
Wiswedel's partner in the clinic, Dr Paul le Roux, is well known in the US for his expertise in assisted pregnancies among older women, and many comments on different websites attest to the fact.

The Cape Fertility Clinic found itself in hot water three years ago when a US website offered a picture catalogue of South African women wanting to sell their eggs for fertility treatments, which would be performed at the local clinic.

In 2004, when the controversy broke, Wiswedel told the Cape Argus he and Le Roux had nothing to do with choosing the couples or providing the donors advertised on the website.

He said then that he had alerted Robin Newman, head of the US company, to his concern that she was not operating within the South African guidelines.

According to the website of the Cape Fertility Clinic, fertility treatment is legally governed by the National Health Bill, signed into law in 2004. It regulates all egg donations, "and the procedure is legal in this country".

But Dr Paul Dalmeyer, head of the Port Elizabeth Fertility Clinic and an executive member of the International Federation of Fertility Societies, described the birth to the 60-year-old woman as "pushing the envelope".

The New Jersey woman and her husband, Ken Birnbaum, 63, already had three children, including two adult children aged 33 and 29. She was quoted as saying she wanted siblings for her six-year-old son, Ari.

In overseas press reports, it emerged that she had previously had eggs frozen, but declined to say whether these were used for the latest pregnancy.

The birth of the twins made Birnbaum the oldest woman in the US to give birth to twins.

Although many local specialists were loath to enter the age debate, it emerged that it was generally accepted that it was ethical to offer fertility treatment to women only until their early 40s.

In the US there are no federal standards for age limits on in-vitro fertilisation, but the Society for Assisted Reproductive Technology there recommends that women be under 50 if the treatment involves a donor egg, and under 44 if they are using their own eggs.

In France, Wikipedia reports, the country approved a bill in the 1990s which prohibits post-menopausal pregnancy, which the French health minister at the time, Philippe Douste-Blazy, called "immoral as well as dangerous to the health of mother and child".

In Italy, the Association of Medical Practitioners and Dentists prevents its members from giving fertility treatment to women aged 50 and older. In spite of the law, though, in 1994 Italian woman Rosanna Della Corte gave birth to a son at age 62 after intervention by doctor Severino Antinori.

She used a donor egg and her husband's sperm, fell pregnant on the first attempt, but miscarried after 40 days. It took six more attempts before the successful birth.

In 2006, the same doctor helped the United Kingdom's Patricia Rashbrook fall pregnant and she gave birth to a son at the age of 62.

The birth sparked a major debate in the UK over the ethics of late motherhood.

Dalmeyer, who was the local organiser of the recent World Congress on Fertility and Sterility in South Africa, said legislation in South Africa was much more lenient than in other countries.

He questioned whether the treatment here for Birnbaum was exploiting the local legislation.

"When the Italian situation occurred in 1994 I can tell you that the international federation was certainly not impressed.

"The general feeling is definitely that this type of procreation and reproduction is not okay," Dalmeyer said.

Men who wait until they are older to have children are not only risking difficulities conceiving they are increasing the risk of genetic problems

Mutations in the fibroblast growth factor receptor 3 (FGFR 3) gene (above) have been linked to achondroplasia, or dwarfism. Sperm analysis shows that mutations associated with dwarfism gradually increased by about two per cent for every year of age.



June 5, 2006
NR-06-06-01

Study shows that genetic quality
of sperm deteriorates as men age

New research indicates that the genetic quality of sperm worsens as men get older, increasing a man’s risk of being infertile, fathering unsuccessful pregnancies and passing along dwarfism and possibly other genetic diseases to his children.

A study led by scientists at Lawrence Livermore National Laboratory (LLNL) and the University of California, Berkeley, found a steady increase in sperm DNA fragmentation with increasing age of the study participants, along with increases in a gene mutation that causes achondroplasia, or dwarfism. The first changes were observed in men in their early reproductive years.


LANL
Mutations in the fibroblast growth factor receptor 3 (FGFR 3) gene (above) have been linked to achondroplasia, or dwarfism. Sperm analysis shows that mutations associated with dwarfism gradually increased by about two per cent for every year of age.
Earlier research by the same team indicated that male reproductive ability gradually worsens with age, as sperm counts decline and the sperm lose motility and their ability to swim in a straight line. In the current study, the researchers analyzed DNA damage, chromosomal abnormalities and gene mutations in semen samples from the same subjects – 97 healthy, non-smoking LLNL employees and retirees between 22 and 80 years old – and found that sperm motility showed a high correlation with DNA fragmentation, which is associated with increased risk of infertility and a reduced probability of fathering a successful pregnancy.

The study, “Advancing age has differential effects on DNA damage, chromatin integrity, gene mutations, and aneuploidies (chromosome abnormalities) in sperm,” appears this week in the online edition of the Proceedings of the National Academy of Sciences.

“This study shows that men who wait until they’re older to have children are not only risking difficulties conceiving, they could also be increasing the risk of having children with genetic problems,” said co-lead author Andrew Wyrobek of LLNL.

“We know that women have a biological time clock,” said co-lead author Brenda Eskenazi of UC Berkeley’s School of Public Health, “with an increase in risk of miscarriage and producing children with trisomy (an extra chromosome, such as in Down’s syndrome) as women age, and with a seemingly abrupt end of fertility around perimenopause. Our research suggests that men, too, have a biological time clock – only it is different. Men seem to have a gradual rather than an abrupt change in fertility and in the potential ability to produce viable healthy offspring.”



May 2007 PATERNAL AGE AND AUTISM ARE ASSOCIATED IN A FAMILY-BASED SAMPLE

: Mol Psychiatry. 2007 May;12(5):419-421.Paternal age and autism are associated in a family-based sample.Cantor RM, Yoon JL, Furr J, Lajonchere CM.
[1] 1Department of Human Genetics, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, CA, USA [2] 2Department of Pediatrics, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, CA, USA [3] 3AGRE Consortium, Los Angeles, CA, USA.

PMID: 17453057 [PubMed - as supplied by publisher]


The paternal age distribution of the AGRE fathers, whose first child is autistic differs significantly from that of the 'control' sample (P=0.005). A 2 goodness-of-fit test with 2 degrees of freedom was conducted using percents in the 'control' group age categories to calculate the expected values in the AGRE sample. The shift toward higher paternal ages in those with an affected first-born is seen most dramatically in the group of AGRE fathers who are 30–39 years inclusive, which is 54.7% of the distribution compared with the 41.9 % that is expected. We interpret this shifted age distribution to provide support for the recently reported finding by Reichenberg and co-workers that autism risk is associated with advancing paternal age.
Labels: CM Lajonchere, J Furr, JL Yoon, RM Cantor

OLDER DADS PAST 33 THE RISKS RISE WITH INCREASING PATERNAL AGE

The link between schizophrenia and older paternity had been made before, but this was the first large study to look at a range of factors that could confound the results, said Professor John McGrath, a psychiatric epidemiologist at the Queensland Centre for Mental Health Research.

"If all babies had fathers less than 30, the paper suggests, the incidence of schizophrenia would reduce by 15 per cent," he said.

In 2002 the average age of fathers was 32, compared with an average age of 29 in 1982, according to data from the Australian Bureau of Statistics.

The executive director of the mental health lobby group SANE Australia, Barbara Hocking, said the Swedish research, published in the British medical journal BMJ, was "major, major stuff".

She likened the research to the link between mothers over 35 and an increased risk of Down syndrome in their children. "It helps people understand what risk factors may be, so you can take action to reduce them."




Obstetrics & Gynecology 1981;57:745-749
© 1981 by The American College of Obstetricians and Gynecologists


Genetic disease in the offspring of older fathers
JM Friedman


Autosomal dominant genetic diseases may result from the transmission of a trait by a carrier parent or from gene mutation in one of the gametes from which the child develops. The mean age of fathers of affected persons has been found to be greater than expected for several autosomal dominant diseases due to new mutations. To assess the clinical importance of this observation, the relative and absolute frequencies of offspring with autosomal dominant diseases due to mutation in the sperm from fathers of various ages have been calculated. The relative frequency of new autosomal dominant mutations in children increases logarithmically with paternal age during the usual years of fatherhood. The absolute frequency of autosomal dominant disease due to new mutations among the offspring of fathers who are 40 years of age or older is estimated to be at least 0.3 to 0.5%. This risk is many times greater than that for children of young fathers and is similar in magnitude to the risk of Down syndrome among the offspring of 35- to 40-year-old mothers. Thus, it is good public health policy to recommend that both men and women complete their family a before age 40, if possible.




Combined Effect of Older Mothers and Fathers Increases Baby's Risk
By Jennifer Warner
WebMD Medical NewsReviewed by Brunilda Nazario, MDJuly 1, 2003 -- Older fathers may contribute just as much as older mothers to the dramatic increase in Down syndrome risk faced by babies born to older couples. A new study found that older fathers were responsible for up to 50% of the rise in Down syndrome risk when the mother was also over 40.

Researchers say the number of births to parents over age 35 has more than doubled in the last 20 years and this has raised questions about the role of paternal age in the risk of genetic abnormalities and birth defects.

Previous studies have shown that the risk of a woman having a baby with Down syndrome rises dramatically after she reaches 35. Although this effect of maternal age on Down syndrome risk is well known, researchers say the influence of the father's age on Down syndrome has not yet been defined. Some studies have found no relationship, while other, smaller studies have suggested that older fathers may raise the risk of Down syndrome.

But researchers say this study, published in The Journal of Urology, is the largest of its kind and looked at 3,429 Down syndrome cases reported to the New York State Department of Health from 1983 to 1997. Their findings suggest that the increase in the number of babies with the genetic abnormality born to women over 35 may be the result of a combined effect of both advanced maternal and paternal ages.

Older Fathers Face More Risks
The study showed that the percentage of births to women over 35 grew from 8% of all births in 1983 to 17% in 1997, and the greatest change during this period was the number of births to mothers and fathers over 40 years old, which rose by 178% and 73%, respectively.

Researchers found that the rate of Down syndrome among parents over 40 was 60 per 10,000 births, which is six times higher than the rate found among couples under 35 years old. Older fathers over 40 had twice the rate of Down syndrome births compared with men 24 years old and younger when they had children with women over 35.

"Paternal age has an effect on Down syndrome but only in mothers 35 years old and older," write researcher Harry Fisch, MD, of the department of urology at Columbia-Presbyterian Medical Center in New York City, and colleagues. "In younger women, in whom age was not a risk factor for Down syndrome, there was no paternal effect."

Among older mothers over 40, researchers found that an increase of 50% in Down syndrome risk was attributable to the advanced age of the father.

In fact, researchers suggest that there is only a modest increase in Down syndrome risk for women 35-39 compared with women 30-35 years old, but the dramatic increase in Down syndrome births among women 35 to 39 years old is largely due to the influence of older fathers because older women tend to make babies with older men.

THE IDEA THAT GERM LINE CNVs OCCUR IN THE SPERM OF OLDER MEN IS CERTAINLY A POSSIBILITY AND A VERY IMPORTANT RESEARCH LINE TO FOLLOW IN SZ AND AUTISM

"The idea that germ line CNVs occur in the sperm of older men (or women for that matter) is certainly possible and a very important research line to follow in schizophrenia and autism. However, the best experiment would be to identify de novo CNVs in patients with SZ by doing CGH and comparing the results with parental CGH (as recently reported by Sebat et al in autism). The possibility of a finding might increase if sporadic, non-familial cases are used. One cannot examine the sperm directly because the frequency of such a defect would be very low and the spermatozoan with a new CNV would be diluted by a large population of cells that do not have it. The sensitivity of current methods used to assess CNV are too low to detect such changes."

A MAJOR INFLUENCE ON NEW MUTATIONS IN THE HUMAN GENE POOL IS RELATED TO THE ADVANCING AGE OF FATHERS

"As a major influence on new mutations in the human gene pool is related to the advancing age of fathers, Dr. Malaspina first examined the relationship of schizophrenia and paternal age. Data showed a strong escalation in schizophrenia risk as the age of the father increased, accounting for over a quarter of the schizophrenia cases. Another of her studies found that fathers of sporadic schizophrenia cases were 5 years older than familial case fathers. If sporadic schizophrenia can originate from new mutations, then neurodevelopmental genes are reasonable candidates. Her study will examine if patients with sporadic schizophrenia, particularly those with fathers older than 35 at birth, show features found in other neurodevelopmental diseases that correlate with paternal age, such as craniofacial abnormalities, nonspecific cognitive deficits and delayed developmental milestones. However, if genes that arise from mutations are inherited by later generations, then some familial cases with a similar illness would not have a paternal age effect. Dr. Malaspina plans to define the clinical profile in sporadic patients associated with paternal age through group comparisons and cluster analysis. If the study is successful, this illness pattern may be useful in gene identification for schizophrenia."


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22 OUT OF 23 PAIRS OF IDENTICAL TWINS BOTH WERE AUTISTIC, 4 OUT OF 17 NON IDENTICAL TWIN WERE BOTH AUTISTIC

1: Am J Psychiatry. 1985 Jan;142(1):74-7. Related Articles, Links


Concordance for the syndrome of autism in 40 pairs of afflicted twins.

Ritvo ER, Freeman BJ, Mason-Brothers A, Mo A, Ritvo AM.
The UCLA Registry for Genetic Studies in Autism was established in 1980 to test the hypothesis that genetic factors may be etiologically significant in subsets of patients. To date 61 pairs of twins have enrolled and 40 meet research diagnostic criteria for autism. The authors found a concordance for autism in these 40 pairs of 95.7% in the monozygotic twins (22 of 23) and 23.5% in the dizygotic twins (four of 17).

BETWEEN 12.4 AND 20.4 PER CENT OF AUTISM SIBLINGS EXHIBITED SOME DEGREE OF AUTISM SPECTRUM IMPAIRMENT

Familial autism


1: J Child Psychol Psychiatry. 1994 Jul;35(5):877-900. Related Articles, Links


A case-control family history study of autism.
Bolton P, Macdonald H, Pickles A, Rios P, Goode S, Crowson M, Bailey A, Rutter M.

M.R.C. Child Psychiatry Unit, Institute of Psychiatry, London, U.K.

Family history data on 99 autistic and 36 Down's syndrome probands are reported. They confirmed a raised familial loading for both autism and more broadly defined pervasive developmental disorders in siblings (2.9% and 2.9%, respectively, vs 0% in the Down's group) and also evidence for the familial aggregation of a lesser variant of autism, comprising more subtle communication/social impairments or stereotypic behaviours, but not mental retardation alone. Between 12.4 and 20.4% of the autism siblings and 1.6% and 3.2% of the Down's siblings exhibited this lesser variant, depending on the stringency of its definition. Amongst autistic probands with speech, various features of their disorder (increased number of autistic symptoms; reduced verbal and performance ability) as well as a history of obstetric complications, indexed an elevation in familial loading. No such association was seen in the probands without speech, even though familial loading for the lesser variant in this subgroup, was significantly higher than in the Down's controls. The findings suggest that the autism phenotype extends beyond autism as traditionally diagnosed; that aetiology involves several genes; that autism is genetically heterogeneous; and that obstetric abnormalities in autistic subjects may derive from abnormality in the foetus.

AUTISM IS GETTING MORE COMMON AS MORE MEN HAVE CHILDREN PAST 33

BRAXTON LEFT REELING BY SON'S AUTISM






TONI BRAXTON discovered her youngest son DIEZEL was autistic when officials at the four-year-old's school in Las Vegas alerted the soul singer to the extent of his learning difficulties. The UNBREAK MY HEART singer felt sure something was wrong when Diezel failed to progress like his older brother, DENIM, but doctors simply assured her the tot was a slow learner with a possible hearing problem. Braxton put her son in speech therapy classes, but had no idea he was autistic until the dean of his private school asked to speak to her late last year (06), shortly after she had begun her residency at Vegas' Flamingo hotel and casino complex. She recalls, "The dean called and said, 'You need to come pick him up, he's not ready for this school.' "I didn't know what to think... They gave us a card and said, 'Call (disability organisation) Child Find in Vegas,' and we called them and they are the one that diagnosed him being autistic."
Singer Toni Braxton opens up about her family life. Toni is married to Keri Lewis They have two sons Demin Cole, 4 1/2 & Diezel Ky, 3 1/2. Toni speaks out about her everday challenges of being a mother, and getting her son Diezel diagnosed with autism. Braxton had a hard time getting the doctors to diagnose her son, and feels the three year old could have been helped if the neurological disorder was spotted earlier. Toni is upset with the Doctors, stating "They dismissed me. I don't know if it would have made a difference or not to be diagnosed earlier, but they had a "wait and see" attitude. It makes me so angry because a mother knows when something is wrong with her child."

Children Born to Couples who have IVF are more likely to be autistic, have cancers, cerebral palsy and mental retardation

THE ARTICLE DOESN'T POINT OUT THAT THIS IS DUE TO THE AGE OF THE FATHER IN MOST CASES


Children born
after IVF treatment 'face higher health risks'


Ian Sample in New Orleans
Thursday October 26, 2006
The Guardian


Children born to couples who have undergone fertility treatment are more likely to be diagnosed with autism, cancer and other disorders such as cerebral palsy and mental retardation, researchers claimed yesterday.
The higher risk to child health is believed to be caused by medical problems in the parents, such as diabetes and hypertension, damaging the child in the womb, but doctors conducting the study said IVF and other fertility treatments may also play a role. Medical records of children born after their parents sought fertility treatment showed they were four times more likely to have autism than those born to fertile parents. Childhood cancers including leukaemia and brain tumours also rose.

The risk of more minor problems, such as attention deficit hyperactivity disorder, rose by 40%, and other medical conditions affecting hearing and sight nearly doubled. Children had a 30% higher chance of being admitted to neonatal intensive care units and to stay in hospital for more than three days if they were born following fertility treatment, the study found.

The researchers stressed the figures represent relative risks. In July researchers at Guy's and St Thomas' hospital in London reported the prevalence of autism to be 0.39% in the general population, a figure that will include some children born to parents aided by fertility treatment. A fourfold rise in the risk of autism would see a child's chances of having the condition increase to 1.56%.

Mary Croughan at the University of California in San Francisco studied 2,000 women who either gave birth naturally after a long period of infertility, or conceived after a variety of fertility treatments, and compared them with 2,000 fertile mothers who gave birth between 1994 and 1998. More than 19,000 medical records were used to build up a picture of the women's pregnancies and deliveries and the health of their children up to six years of age.

The researchers found infertile women had more complications such as pre-term labour and pre-eclampsia, more delivery difficulties and caesarean sections. Children born to infertile women were 20% more likely to have low birth weights and were twice as likely to show evidence of poor growth in the womb. Speaking at the American Association for Reproductive Medicine (ASRM) conference in New Orleans, Dr Croughan said that medical conditions more common in infertile couples may be to blame for the rise in childhood health problems. She said: "The vast majority of children born to infertile couples are healthy, but if a couple has any risk factors that could lead to a child not being born healthy, then those should of course be taken into consideration."

Clare Brown, chief executive of Infertility Network UK, said "continual research" was needed to ensure "treatment is safe for couples and potential children".

ALTHOUGH INFERTILE MEN MAY FATHER CHILDREN WITH ASSISTED CONCEPTION, FERTILIZATION WITH DNA-DAMAGED SPERMATOZOA MAY INCREASE RISK OF GENETIC DISEASE

Fertil Steril. 2001 Apr;75(4):674-7. Links
Correlations between two markers of sperm DNA integrity, DNA denaturation and DNA fragmentation, in fertile and infertile men.Zini A, Bielecki R, Phang D, Zenzes MT.
Division of Urology, Department of Surgery, University of Toronto, Ontario, Toronto, Canada. azini@mtsinai.on.ca

OBJECTIVE: To evaluate two different assays of human sperm DNA integrity, DNA denaturation (DD) and DNA fragmentation (DF), and to correlate these with standard semen parameters. DESIGN: Prospective, observational study. SETTING: University infertility clinic.Patient(s): Forty consecutive semen samples from 33 nonazoospermic men presenting for infertility evaluation and 7 fertile men presenting for vasectomy. Intervention(s): Assessment of sperm concentration, motility, morphology, DD and DF. MAIN OUTCOME MEASURE(S): Sperm DD and DF in fertile and infertile men. RESULT(S): The mean (+/-SE) rates of DD and DF were significantly higher in infertile subjects compared to fertile controls, respectively: 25.4 +/- 3.0 vs. 10.2 +/- 2.3 (P=.028) and 27.6 +/- 2.5 vs. 13.3 +/- 2.5% (P=.016). DF and DD correlated strongly (r = 0.71, P<.0001). Also, DD and DF correlated negatively with standard semen parameters (concentration, motility, and morphology), the strongest correlation being with sperm motility. CONCLUSION(S): The strong correlation between sperm DD and DF, and the higher levels of sperm DNA damage in infertile compared with fertile men, indicate that male infertility is associated with poor sperm DNA integrity. Although infertile men may father children with assisted conception, fertilization with DNA-damaged spermatozoa may increase the risk of genetic disease in the offspring.




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PEDIATRICS Vol. 113 No. 5 May 2004, pp. e472-e486


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The Genetics of Autism
Rebecca Muhle, BA*, Stephanie V. Trentacoste, BA* and Isabelle Rapin, MD

* Class of 2004, Albert Einstein College of Medicine, Bronx, New York
Saul R. Korey Department of Neurology, Department of Pediatrics, and Rose F. Kennedy Center for Research in Mental Retardation and Human Development, Albert Einstein College of Medicine, Bronx, New York




Epilepsy has the highest association with autism, reported in up to a third of individuals with an ASD by adulthood.25–27,33–35 The epilepsy may be subclinical, yielding an electroencephalogram that is epileptiform but without clinical seizures, and is particularly frequent in disintegrative disorder.36 Like autism, epilepsy is a disorder of the brain with multiple genetic and nongenetic causes and a broad range of phenotypes. Infantile spasms are particularly likely to result in autism with nondevelopment of language and mental retardation, especially when the epileptiform activity involves both temporal lobes.37 An occasional nonverbal child with mental retardation, autism, and epilepsy has exhibited early bilateral hippocampal sclerosis.38,39

Behavioral symptoms of autism are frequent in tuberous sclerosis complex (TSC) and fragile X syndrome (FXS), but these 2 disorders nevertheless account for only a minority of the total cases of autism.40,41 Given the high rate of epilepsy in children with TSC and the association between autism and epilepsy, it is perhaps not surprising that as many as 25% of patients with TSC have autism.42,43 An autosomally dominant neurocutaneous disorder, TSC arises from genetic mutations of either TSC1 on 9q or TSC2 on 16p and is characterized by ash-leaf depigmented or other cutaneous manifestations and hamartomatous lesions in multiple organs. In the brain, these lesions are termed tubers, and they are thought to cause the epilepsy seen in more than three quarters of children with TSC.44,45 Furthermore, it is the haphazard distribution of these tubers, together with other metabolic changes, that influences the phenotype of TSC, giving rise in some individuals to autism or epilepsy (often infantile spasms).37 In the population of patients with autism, numerous studies have quoted TSC rates of 1.1% to 1.3%,25–27,46 rates that, although low, are 30% higher than the prevalence of TSC in the general population.

FXS is an X-linked genetic disorder that is significantly associated with autism and that is denoted by unusual facial features, macro-orchidism in adulthood, and cognitive impairment of variable severity. It is caused by an increased number of trinucleotide (CGG) repeats in the gene coding for the fragile X mental retardation protein. Approximately 30% of individuals with FXS are on the autistic spectrum.47,48 There is disagreement, however, over the degree of FXS prevalence in patients with autism. Some early studies reported little or no association between FXS and autism,24,49 whereas others found a high association50 (see41 for additional review). More recent epidemiologic studies have documented rates of FXS between 7% and 8% in populations with autism.26,33,51,52 The discrepancies regarding the prevalence of FXS among individuals with autism may reflect the limited reliability of the cytogenetic tests used in the past compared with the more sensitive molecular tests currently used; as such, the number of girls who receive a diagnosis of FXS has increased.6

Genetic mutations that give rise to a number of additional diagnosable diseases may also be associated with autism. Neurofibromatosis, a common autosomal dominant disorder with neurologic and cutaneous manifestations, is much less frequently associated with autism than is TSC or FXS.53 Angelman syndrome (AS) and Prader-Willi syndrome (PWS) usually result from genetic deletions or uniparental disomy (inheritance of both chromosomes from 1 parent) of the chromosome 15q11-q13 locus,54,55 with abnormal imprinting or genetic mutations found in up to 5.1% of PWS cases and up to 15% of AS cases.55 Loss of paternally derived genes results in PWS, whereas AS, more commonly associated with autism than PWS,56,57 can result from the loss or mutation of the maternally derived ubiquitin protein ligase gene UBE3A or the ATP10C gene.58–60 An unexpectedly large proportion of boys with Duchenne muscular dystrophy are on the autistic spectrum.61 Many other rare single-gene defects have been associated with autism in case studies, including those found in Sotos syndrome,62 Williams syndrome,63 hypomelanosis of Ito,64 Cowden syndrome,65 and Moebius syndrome.66,67 We refer the reader to The Biology of the Autistic Syndromes by Gillberg and Coleman (p. 136–184)9 for a more complete listing of rare genetic conditions that are responsible for autism in occasional individuals.

Finally, autism may also occur in the context of abnormal cellular metabolism, such as mitochondrial disease.




Inherited Autism of Unknown Cause: Family Studies
Epidemiologic studies of autism report a prevalence of 5–10 cases of classic autism per 10 000 (some 3–6 per 1000 if the entire spectrum of autism is included) with a male to female ratio of 3:1.3,9,11 The preponderance of males suggests an X-linked disorder, and recent genome-wide screens by 2 separate groups have found evidence of linkage to the X chromosome,78,79 but the data are inconsistent. Cases of male-to-male transmission of autism in multiplex families, however, rule out X-linkage as the predominant mode of inheritance in these families.80,81 Similarly, analysis of Y haplotypes in patients with autism showed no significant associations,82 although Y chromosome abnormalities have been documented in case reports.83

There is strong and convincing evidence from 2 main sources that autism without a diagnosable cause is a heritable disorder. First, the rate of recurrence in siblings of affected individuals is 2% to 8%, much greater than the prevalence rate in the general population.9,27,46 Second, early twin studies in the United Kingdom and Scandinavia reported that monozygotic (MZ) twins had a rate of concordance >60% for classic autism, with no concordance found between dizygotic (DZ) twins.76,77 The higher rate of MZ concordance provides compelling evidence for the strong influence of genetics in the cause of autism, influence that extends well beyond the aforementioned associated genetic disorders. Furthermore, when the unaffected twin discrepant for autism was reevaluated for broader autistic phenotypes, including communication skills and social disorders, the concordance among the UK twins rose remarkably, from 60% to 92% in MZ twins and from 0% to 10% in DZ pairs.76,84 The existence of a susceptible genetic background is also suggested by the preponderance of traits such as obsessive-compulsive disorder, communication disorders, and social phobias in nonautistic family members of patients with autism.85–87 These crucial observations suggest that the interactions of multiple genes cause autism and that there is variable expression of autism-related traits.


.

IT IS LIKELY THAT SPERM WITH DNA DAMAGE CONTRIBUTED TO SUCCESSFUL FERTILZATION AND IN-VITRO DEVELOPMENT, POTENTIAL ADVERSE EFFECTS WHAT ARE THEY?

Human Reproduction, Vol. 17, No. 4, 990-998, April 2002© 2002 European Society of Human Reproduction and Embryology


The spectrum of DNA damage in human sperm assessed by single cell gel electrophoresis (Comet assay) and its relationship to fertilization and embryo development
I.D. Morris1,3, S. Ilott2, L. Dixon1 and D.R. Brison2
1 School of Biological Sciences, University of Manchester, Manchester and 2 Department of Reproductive Medicine, St Mary's Hospital, Manchester, UK

BACKGROUND: The integrity of sperm DNA is important for the success of natural or assisted fertilization, as well as normal development of the embryo, fetus and child. ICSI, by bypassing sperm selection mechanisms, increases the risk of transmitting damaged DNA and the significance of this requires investigation. METHODS: DNA damage in sperm from an unselected group of 60 men undergoing IVF treatment was measured by single cell gel electrophoresis (Comet assay) and correlated with semen and treatment cycle parameters. RESULTS: Wide spectra of sperm DNA damage were found both within and between men but no specific subgroups were identified. Semen and treatment cycle parameters were not different in men grouped according to high or low sperm DNA damage. However, regression analysis showed that DNA damage was positively associated with age (29–44 years), abnormal sperm and motility and negatively associated with sperm concentration. In ICSI cycles DNA damage was positively associated with impairment of post-fertilization embryo cleavage. CONCLUSIONS: This study contributes to the evidence of DNA damage within sperm. High loads of DNA damage measured by the Comet assay were predictive of failure of embryo development after ICSI. As it is likely that sperm with DNA damage contributed to successful fertilization and in-vitro development, potential adverse effects remain to be clarified.

POSSIBILITY THAT PATERNAL SMOKING CAUSES MUTATIONS IN SPERM THAT LEAD TO CANCER, BIRTH DEFECTS, GENETIC DISEASES IN OFFSPRING DNA DAMAGE UP 50%

1: Mutat Res. 1996 Apr 13;351(2):199-203. Links
Smoking and low antioxidant levels increase oxidative damage to sperm DNA.Fraga CG, Motchnik PA, Wyrobek AJ, Rempel DM, Ames BN.
Fisicoquimica, Facultad de Farmacia y Bioquimica, Universidad de BuenosAires, Argentina.

Our previous studies have shown that men with low ascorbate intake have markedly increased oxo8dG in the DNA of their sperm. Because cigarette smoke is high in oxidants and depletes plasma and tissue antioxidants, oxidative DNA damage in sperm and tocopherol and ascorbate levels in seminal plasma were determined in smokers and non-smokers. The level in sperm DNA of oxo8dG, an oxidative lesion of guanine, was 50% higher in smokers compared to nonsmokers (p = 0.005). The concentration of alpha-tocopherol in seminal plasma was decreased in smokers by 32% (p = 0.03). Smoking and low antioxidant levels increase oxidative damage to sperm DNA. We discuss the possibility that paternal smoking causes mutations in sperm that lead to cancer, birth defects, and genetic diseases in offspring.

PMID: 8622715 [PubMed - indexed for MEDLINE]

Slight but significant increases in disomy frequency with advancing paternal age were observed for some chromosomes, in particular for sex chromosomes

Aneuploidy in human sperm: a review of the frequency and distribution of aneuploidy, effects of donor age and lifestyle factors
Q. Shi, R.H. Martin

Department of Medical Genetics, Faculty of Medicine, University of Calgary, and Genetics Department, Alberta Children's Hospital, Calgary, Alberta (Canada)


Abstract.

Application of fluorescence in situ hybridization (FISH) analysis has opened the way for comprehensive studies on numerical chromosome abnormalities in human sperm. During the last decade, more than five million sperm from approximately 500 normal men were analyzed by a number of laboratories from around the world by this approach. Except for chromosome 19 which has been analyzed in only one study, all other chromosomes have been examined by two or more studies with considerable differences in disomy frequency for an individual chromosome among studies. The mean disomy frequency is 0.15% for each of the autosomes and 0.26% for the sex chromosomes. Most chromosomes analyzed have an equal distribution of disomy with the exception of chromosomes 14, 21, 22 and the sex chromosomes, which display significantly higher disomy frequencies. Slight but significant increases in disomy frequency with advancing paternal age were observed for some chromosomes, in particular for the sex chromosomes. Some lifestyle factors such as smoking, alcohol drinking and caffeine consumption have been investigated and no consistent association between disomy frequency and any type of lifestyle factors has been established. The question of whether different geographic and ethnic groups of men have inherent differences in frequency of disomic sperm has been investigated by two studies with conflicting results.

Copyright © 2000 S. Karger AG, Basel


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Autoimmune Quotient

Source: American Autoimmune Related Diseases Association (AARDA) Released: Wed 23-May-2007, 16:05 ET
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Do You Know Your Family AQ?
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AUTOIMMUNE DISEASE, AQ, AUTOIMMUNE QUOTIENT, FAMILY MEDICAL HISTORY, MAJOR HEALTH CRISIS, WOMENS HEALTH
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The American Autoimmune Related Diseases Association (AARDA) wants to help you learn your family’s AQ. AQ is a play on IQ and stands for Autoimmune Quotient. It’s about knowing how likely you or a loved one is to develop an autoimmune disease, based on the prevalence of these diseases and your family history.






Newswise — The American Autoimmune Related Diseases Association (AARDA) wants to help you learn your family’s AQ. AQ is a play on IQ and stands for Autoimmune Quotient. It’s about knowing how likely you or a loved one is to develop an autoimmune disease, based on the prevalence of these diseases and your family history.

AARDA offers the following advice to help you determine your family’s AQ:

1. Understand that autoimmune diseases constitute a major U.S. health crisis. According to the National Institutes of Health (NIH), there are 23.5 million Americans who suffer from autoimmune diseases and the prevalence of these diseases is rising. In comparison, cancer affects up to 9 million and heart disease up to 22 million. Collectively, autoimmune disease is one of the top 10 leading causes of death in children and women under 65 and represents some $100 billion in annual direct health care costs. Yet, fewer than 6 percent of Americans surveyed in a recent AARDA/Roper poll could identify an autoimmune disease.

2. Get educated.
There are more than 80 known autoimmune diseases and an additional 40 diseases that are suspected to be autoimmune-related. The diseases themselves can affect almost any part of the body, including the kidneys, skin, heart, liver, lymph nodes, thyroid and the central nervous system. As a result, they cut across various medical specialties, such as endocrinology, neurology, dermatology, rheumatology, gastroenterology and hematology, among others. Autoimmune diseases include multiple sclerosis, myasthenia gravis, scleroderma, polymyositis, vasculitis, lupus, Sjögren's disease, idiopathic thrombocytopenic purpura (ITP), type 1 or juvenile diabetes, Crohn’s disease and Graves’ disease.

Autoimmunity is the underlying cause of these diseases. It is the process whereby the immune system mistakenly recognizes the body's own proteins as foreign invaders and begins producing antibodies that attack healthy cells and tissues, causing a variety of diseases.

Visit http://www.aarda.org for more detailed information and a complete disease list.

3. Be aware that autoimmune diseases target women.
Women are more likely than men to be affected; some estimates say that 75 percent of those affected are women. These women are usually in the childbearing years. In the past several years, autoimmunity has begun to be recognized as a major women’s health issue, with the Office of Research on Women’s Health at NIH recognizing it as such and the Society for Advancement of Women’s Health Research naming it as one of 10 diseases that most disproportionately affect women.

4. Know that autoimmune diseases run in families.
Current research points to a genetic component in autoimmune diseases. However, autoimmune diseases are not typical genetic diseases like, for instance, sickle cell anemia, where there is a specific gene mutation. With autoimmune diseases, multiple genes are involved that collectively increase vulnerability or susceptibility. Thus, what is inherited is not one specific gene but several genes that increase risk. As a result, autoimmune diseases tend to “cluster” in families - not as one particular disease, but as a general tendency to the autoimmune process and, consequently, different autoimmune diseases. For example, one family member may have autoimmune hepatitis; another, celiac disease; another, rheumatoid arthritis.

5. Do your own family medical history.
Given the family connection, knowing the health histories of other family members is critical. For example, if your grandmother or father or sister or uncle has an autoimmune disease, you could be more susceptible to developing one yourself. Take an inventory of your family health problems, expanding your research beyond your immediate family to include grandparents, aunts, uncles, cousins and other relatives. Once you know your family history, share it with other family members and your doctor who can then assess the possibilities with a degree of accuracy and order appropriate tests.

6. Keep a "symptoms" list.
People with autoimmune diseases often suffer from a number of symptoms that, on the surface, seem unrelated. In addition, they may have suffered from other seemingly unrelated symptoms throughout their lives. It is important, therefore, to make a list of every major symptom you’ve experienced so that you can present it clearly to your doctor. List the symptoms in the order of concern to you.

7. Realize that getting an autoimmune disease diagnosis is often challenging.
An AARDA study of autoimmune patients found that the average time for diagnosis of a serious autoimmune disease is 4.6 years. During that period, the patient typically has seen 4.8 doctors; and 46 percent of the patients were told initially that they were too concerned about their health or that they were chronic complainers.

One of the factors that makes getting a correct autoimmune disease diagnosis so difficult is that symptoms can vary widely, notably from one disease to another, but even within the same disease. Also, because autoimmune diseases affect multiple systems, their symptoms can often be misleading.

The medical community’s lack of knowledge of autoimmune disease compounds the problem. Even though these diseases share a genetic background and tend to run in families, most health questionnaires at doctors’ offices do not ask whether there is a family history of autoimmune disease.

8. Hold the power to protect your family’s future health and well-being in your hands.

Congratulations! By working through these steps and doing your homework, you now have the knowledge to determine whether you or your loved ones could be at risk for developing an autoimmune disease.



Emmy Nominated Actress Kellie Martin Stars in New Autoimmunity PSA Campaign
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The American Autoimmune Related Diseases Association (AARDA) launched its first-ever national public service (PSA) campaign titled, “Know Your Family AQ,” starring well-known actress and longtime AARDA spokesperson Kellie Martin.







Newswise — The American Autoimmune Related Diseases Association (AARDA) launched its first-ever national public service (PSA) campaign titled, “Know Your Family AQ,” starring well-known actress and longtime AARDA spokesperson Kellie Martin.

Unveiled on the steps of the U.S. Capitol at a patient rally earlier this week during National Autoimmune Diseases Awareness Month, the multi-media PSA campaign consists of 30-second radio and television spots, as well as a video interview with Martin (visit www.aarda.org to view/listen to all campaign elements). It is designed to educate Americans about the existence of the close genetic relationship and common pathway of disease among autoimmune diseases, which helps explain the clustering of these diseases in individuals and throughout families.

“AQ is a play on IQ and stands for Autoimmune Quotient. How likely are you or a loved one to develop an autoimmune disease? Given the family connection, knowing the health histories of other family members could help answer that question,” said Martin, who currently stars in The Hallmark Channel’s Mystery Woman series. “For example, if your grandmother or father or sister or uncle has an autoimmune disease, you could be more susceptible to developing one yourself. Therefore documenting and sharing your family’s medical history or AQ is key.”

Martin explained her starring role in the campaign, “As a new mom and someone whose family has been touched by autoimmune disease, I want all Americans to understand why knowing their family AQ is so vitally important.”

Martin’s sister Heather passed away at the age of 19 from a misdiagnosed case of lupus in 1998.

“Unfortunately, the Martin family’s experience is not uncommon since autoimmune diseases are often very difficult to diagnose,” added Virginia Ladd, president and executive director, AARDA. “Symptoms can be sporadic and seemingly unconnected and the diseases can affect almost any part of the body with unpredictable patterns of flare-ups and remissions. Thus most autoimmune diseases are diagnosed by a combination of blood work, clinical findings and a careful history, not only of symptoms, but also of a detailed family medical history.”

About Autoimmunity and National Autoimmune Diseases Awareness Month
There are more than 80 known autoimmune diseases including multiple sclerosis, myasthenia gravis, scleroderma, polymyositis, vasculitis, lupus, idiopathic thrombocytopenic purpura (ITP), juvenile diabetes, Sjögren's disease, Crohn’s disease and Graves' disease. Autoimmunity is the underlying cause of these diseases. It is the process whereby the immune system mistakenly recognizes the body's own proteins as foreign invaders and begins producing antibodies that attack healthy cells and tissues, causing a variety of diseases.

According to the National Institutes of Health (NIH), there are 23.5 million Americans who suffer from autoimmune diseases and the prevalence of these diseases is rising. Collectively, autoimmune disease is one of the top 10 leading causes of death in children and women under 65 and represents some $100 billion in annual direct health care costs. Yet, fewer than six percent of Americans surveyed in a recent AARDA/Roper poll could identify an autoimmune disease.

To help raise Americans’ awareness of these diseases, the Senate recently designated May as National Autoimmune Diseases Awareness Month.

About American Autoimmune Related Diseases Association
American Autoimmune Related Diseases Association (AARDA) is the nation's only non-profit organization dedicated to bringing a national focus to autoimmunity as a category of disease and a major women's health issue, and promoting a collaborative research effort in order to find better treatments and a cure for all autoimmune diseases. For more information, please visit http://www.aarda.org or call 586-776-3900 or 888-856-9433.

About Kellie Martin
A seasoned television veteran at 31, Martin began pursuing an acting career at the tender age of seven. To date, Martin, who has been dubbed “One of Hollywood’s 10 Best Loved Stars,” has accrued an impressive list of credits and achievements. She is probably still most fondly remembered for her work as “Becca Thacher” in the popular ABC series Life Goes On for which she received an Emmy nomination for Best Supporting Actress. Martin later appeared as third-year medical student “Lucy Knight” on NBC-TV’s smash hit ER and, today stars as “Samantha Kinsey” on The Hallmark Channel’s Mystery Woman series.




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Kabuki Syndrome in 48 well-defined new individuals our data show it is underrepresented in young fathers and overrepresented in older fathers

Am J Med Genet A. 2005 Jan 30;132(3):265-72. Links
Further delineation of Kabuki syndrome in 48 well-defined new individuals.Armstrong L, Abd El Moneim A, Aleck K, Aughton DJ, Baumann C, Braddock SR, Gillessen-Kaesbach G, Graham JM Jr, Grebe TA, Gripp KW, Hall BD, Hennekam R, Hunter A, Keppler-Noreuil K, Lacombe D, Lin AE, Ming JE, Kokitsu-Nakata NM, Nikkel SM, Philip N, Raas-Rothschild A, Sommer A, Verloes A, Walter C, Wieczorek D, Williams MS, Zackai E, Allanson JE.
Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada. llarmstrong@cw.bc.ca

Kabuki syndrome is a multiple congenital anomaly/mental retardation syndrome. This study of Kabuki syndrome had two objectives. The first was to further describe the syndrome features. In order to do so, clinical geneticists were asked to submit cases-providing clinical photographs and completing a phenotype questionnaire for individuals in whom they felt the diagnosis of Kabuki syndrome was secure. All submitted cases were reviewed by four diagnosticians familiar with Kabuki syndrome. The diagnosis was agreed upon in 48 previously unpublished individuals. Our data on these 48 individuals show that Kabuki syndrome variably affects the development and function of many organ systems. The second objective of the study was to explore possible etiological clues found in our data and from review of the literature. We discuss advanced paternal age, cytogenetic abnormalities, and familial cases, and explore syndromes with potentially informative overlapping features. We find support for a genetic etiology, with a probable autosomal dominant mode of inheritance, and speculate that there is involvement of the interferon regulatory factor 6 (IRF6) gene pathway. Very recently, a microduplication of 8p has been described in multiple affected individuals, the proportion of individuals with the duplication is yet to be determined. (c) 2004 Wiley-Liss, Inc.

PMID: 15690370 [PubMed - indexed for MEDLINE]



1: Am J Med Genet A. 2005 Jan 30;132(3):260-2. Links
Autoimmune disorders in Kabuki syndrome.Ming JE, Russell KL, McDonald-McGinn DM, Zackai EH.
Division of Human Genetics and Molecular Biology, Department of Pediatrics, The Children's Hospital of Philadelphia and The University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA. jeming@mail.med.upenn.edu






Kabuki syndrome is associated with abnormalities in multiple organ systems. While many of the anomalies are congenital malformations, other clinical manifestations may not appear until later in childhood. Among these associated conditions, autoimmune abnormalities have been described in several patients. These include idiopathic thrombocytopenic purpura (ITP), hemolytic anemia, thyroiditis, and vitiligo. In this report, we describe five affected patients with autoimmune manifestations. Four patients had ITP, and two of these patients had concurrent hemolytic anemia. The fifth patient had vitiligo. Two of the patients with ITP had a chronic and relapsing course. Of note, some of these patients also had hypogammaglobulinemia. The autoimmune disorders may be manifestations of abnormal immune regulation. We conclude that Kabuki syndrome is associated with an increased incidence of autoimmune disorders. In addition, the presence of an underlying immune defect may predispose these children to a chronic course of these autoimmune conditions. (c) 2004 Wiley-Liss, Inc.

PMID: 15523604 [PubMed - indexed for MEDLINE]




Paternal Age
Data from the study and the literature suggest an association with advanced paternal age. The average paternal and maternal ages in this study are 34 years (n = 39) and 28.9 years (n = 42), respectively. The average paternal age did not vary with birth year (data not shown). the same data and effect in a complimentary way. These plots show that observed Kabuki syndrome births are underrepresented in young fathers (where the ratios are below one) and overrepresented in older fathers (where the ratios are above one). In the absence of a parental age effect, the ratio would be approximately one across all ages, which is the pattern seen for the maternal age data.




. The average paternal ages of all series are greater than the US means derived from vital statistics, and the mean paternal age of 27 years quoted by The American College of Medical Genetics in their Statement of Guidance for Genetic Counseling in Advanced Paternal Age [American College of Medical Genetics Statement on Guidance for Genetic Counseling in Advanced Paternal Age, [1996]]. has an average paternal age below its control paternal age; however, interpretation may require caution. Firstly, there is evidence that this series is causally heterogeneous, including, for example, children with chromosome abnormalities (2 of 62 have unbalanced karyotype). Secondly, the authors indicate that some of the individuals resembled a parent. If these represent non-sporadic diagnoses, their inclusion would dilute any paternal age effect.





Conditions including achondroplasia, Apert syndrome, Crouzon syndrome, Pfeiffer syndrome, and the type 2 multiple endocrine neoplasias show strong paternal mutation bias and paternal age effects. Each is due to a point mutation. Other disorders such as neurofibromatosis type 1 show a milder paternal mutation bias and paternal age effect, and the disease causing mutations are heterogeneous with point mutations comprising a subset [Crow, [2000]]. Our data suggest that Kabuki syndrome may be related to mutations associated with paternal aging.
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Reviews Genetics 1, 40-47 (2000); doi:10.1038/35049558


THE ORIGINS, PATTERNS AND IMPLICATIONS OF HUMAN SPONTANEOUS MUTATION
James F. Crow

Summary

Germline base substitution mutations occur more frequently in males than in females, especially in older males.
The main explanation for the sex and age effect is that a much larger number of germline divisions occurs in the male than in the female, and continues throughout male adulthood.
Point mutations at some loci occur almost exclusively in males, whereas others have a smaller excess, roughly ten times more than in females. Which is more typical remains to be determined.
For mutations other than point mutations, sex biases in the mutation rate are very variable. However, small deletions are more frequent in females.
The total rate of new deleterious mutations for all genes is estimated to be about three per zygote. This value is uncertain, but it is likely that the number is greater than one.
It is suggested that quasi-truncation selection is the principal explanation for how the population can rid itself of a large number of mutations with a relatively low fitness cost.
Since this form of selection is effective only with sexual reproduction, perhaps the fact that humans reproduce sexually has made it possible to have such a long life cycle.




Author biography
James F. Crow received his Ph.D. from the University of Texas in 1941. After seven years at Dartmouth College, he moved to the University of Wisconsin where he has been since and is now emeritus professor of genetics. He is a member of the National Academy of Sciences as well as a foreign member of the Japan Academy. His research interests are in population genetics, both theoretical and experimental. In addition to journal articles, he is the co-author of An Introduction to Population Genetics Theory with M. Kimura.

Advanced Paternal Age was noted for the fathers of patients with Crouzon or Pfeiffer Syndrome 34.50 +/- 7.65 years

OUR RESULTS SUGGEST THAT OLDER FATHERS HAVE ACCUMULATED OR ARE MORE SUSCEPTIBLE TO A VARIETY OF GERM LINE MUTATIONS


Published by the University of Chicago Press

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Title Paternal Origin of FGFR2 Mutations in Sporadic Cases of Crouzon Syndrome and Pfeiffer Syndrome
Author(s) Rivka L. Glaser, Wen Jiang, Simeon A. Boyadjiev, Alissa K. Tran, Andrea A. Zachary, Lionel Van Maldergem, David Johnson, Sinead Walsh, Michael Oldridge, Steven A. Wall, Andrew O. M. Wilkie, and Ethylin Wang Jabs
Identifiers The American Journal of Human Genetics, volume 66 (2000), pages 768–777
DOI: 10.1086/302831
PubMed ID: 10712195

Availability This site: PS | HTML | PDF (303.3k)
Copyright © 2000, The American Society of Human Genetics.
Abstract Crouzon syndrome and Pfeiffer syndrome are both autosomal dominant craniosynostotic disorders that can be caused by mutations in the fibroblast growth factor receptor 2 (FGFR2) gene. To determine the parental origin of these FGFR2 mutations, the amplification refractory mutation system (ARMS) was used. ARMS PCR primers were developed to recognize polymorphisms that could distinguish maternal and paternal alleles. A total of 4,374 bases between introns IIIa and 11 of the FGFR2 gene were sequenced and were assayed by heteroduplex analysis, to identify polymorphisms. Two polymorphisms (1333TA/TATA and 2710 C/T) were found and were used with two previously described polymorphisms, to screen a total of 41 families. Twenty-two of these families were shown to be informative (11 for Crouzon syndrome and 11 for Pfeiffer syndrome). Eleven different mutations in the 22 families were detected by either restriction digest or allele-specific oligonucleotide hybridization of ARMS PCR products. We molecularly proved the origin of these different mutations to be paternal for all informative cases analyzed (P=2.4×10-7; 95% confidence limits 87%100%). Advanced paternal age was noted for the fathers of patients with Crouzon syndrome or Pfeiffer syndrome, compared with the fathers of control individuals (34.50±7.65 years vs. 30.45±1.28 years, P<.01). Our data on advanced paternal age corroborates and extends previous clinical evidence based on statistical analyses as well as additional reports of advanced paternal age associated with paternal origin of three sporadic mutations causing Apert syndrome (FGFR2) and achondroplasia (FGFR3). Our results suggest that older men either have accumulated or are more susceptible to a variety of germline mutations.

Three Sporadic Cases of Achondroplasia average paternal age 35.86 all mutations FGFR-3 on paternally derived chromosome

this study was 35.86 years, suggesting an advanced
paternal age effect.


Mutations in Fibroblast Growth-Factor Receptor 3 in Sporadic Cases of Achondroplasia Occur Exclusively on the Paternally Derived Chromosome
Author(s) Douglas J. Wilkin, Jinny K. Szabo, Rhoda Cameron, Shirley Henderson, Gary A. Bellus, Michelle L. Mack, Ilkka Kaitila, John Loughlin, Arnold Munnich, Bryan Sykes, Jacky Bonaventure, and Clair A. Francomano
Identifiers The American Journal of Human Genetics, volume 63 (1998), pages 711–716
DOI: 10.1086/302000
PubMed ID: 9718331

Availability This site: PS | HTML | PDF (535.4k)
Copyright © 1998, The American Society of Human Genetics.
Abstract More than 97% of achondroplasia cases are caused by one of two mutations (G1138A and G1138C) in the fibroblast growth factor receptor 3 (FGFR3) gene, which results in a specific amino acid substitution, G380R. Sporadic cases of achondroplasia have been associated with advanced paternal age, suggesting that these mutations occur preferentially during spermatogenesis. We have determined the parental origin of the achondroplasia mutation in 40 sporadic cases. Three distinct 1-bp polymorphisms were identified in the FGFR3 gene, within close proximity to the achondroplasia mutation site. Ninety-nine families, each with a sporadic case of achondroplasia in a child, were analyzed in this study. In this population, the achondroplasia mutation occurred on the paternal chromosome in all 40 cases in which parental origin was unambiguous. This observation is consistent with the clinical observation of advanced paternal age resulting in new cases of achondroplasia and suggests that factors influencing DNA replication or repair during spermatogenesis, but not during oogenesis, may predispose to the occurrence of the G1138 FGFR3 mutations.

Asperger's Comorbid Conditions-depression, anxiety, OCD, ADHD, alcoholism, etc.

Advances in Psychiatric Treatment (2004) 10: 341-351
© 2004 The Royal College of Psychiatrists

Asperger syndrome from childhood into adulthood
Tom Berney
Tom Berney is a consultant in developmental psychiatry with the Northgate & Prudhoe NHS Trust (Prudhoe Hospital, Prudhoe, Northumberland NE42 5NT, UK. E-mail: t.p.berney@ncl.ac.uk) and at the Fleming Nuffield Child Psychiatry Unit, Newcastle upon Tyne. He is also honorary consultant to European Services for People with Autism, a registered charity that provides community services.




Asperger syndrome, a form of autism with normal ability and normal syntactical speech, is associated with a variety of comorbid psychiatric disorders. The disorder is well known to child psychiatry, and we are beginning to recognise the extent of its impact in adulthood. The article reviews the diagnosis and assessment of Asperger syndrome and its links with a wide range of psychiatric issues, including mental disorder, offending and mental capacity. It also describes the broader, non-psychiatric management of Asperger syndrome itself, which includes social and occupational support and education, before touching on the implications the disorder has for our services.



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Asperger syndrome comes not only with its own characteristics (Box 1), but also with a wide variety of comorbid conditions such as depression, anxiety, obsessive–compulsive disorder, attention-deficit hyperactivity disorder (ADHD) and alcoholism, and relationship difficulties (including family/marital problems) (Tantam, 2003). It may predispose individuals to commit offences and can affect their mental capacity and level of responsibility as well as their ability to bear witness or to be tried. The syndrome can colour psychiatric disorder, affecting both presentation and management, for children and adults across a wide range of functional ability. Families have taken an active legalistic approach, alleging misdiagnosis and mistreatment and demanding clarity as to the relationship between Asperger syndrome and other diagnostic concepts.




Box 1 Characteristics of Asperger syndrome in adulthood
Childhood onset

Limited social relationships – social isolation


Few/no sustained relationships; relationships that vary from too distant to too intense

Awkward interaction with peers

Unusual egocentricity, with little concern for others or awareness of their viewpoint; little empathy or sensitivity

Lack of awareness of social rules; social blunders

Problems in communication


An odd voice, monotonous, perhaps at an unusual volume

Talking ‘at’ (rather than ‘to’) others, with little concern about their response

Superficially good language but too formal/stilted/pedantic; difficulty in catching any meaning other than the literal

Lack of non-verbal communicative behaviour: a wooden, impassive appearance with few gestures; a poorly coordinated gaze that may avoid the other’s eyes or look through them

An awkward or odd posture and body language

Absorbing and narrow interests


Obsessively pursued interests

Very circumscribed interests that contribute little to a wider life, e.g. collecting facts and figures of little practical or social value

Unusual routines or rituals; change is often upsetting

(After Gillberg et al, 2001)

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Schizophrenia
Despite Asperger’s early intent, it was only in 1971 that autism was distinguished from schizophrenia, although a number of subsequent reports have suggested that it might yet be identified as a predisposing factor. The similarity of Asperger syndrome to a preschizophrenic, schizoid personality disorder as well as to residual schizophrenia, in both clinical presentation and neurobiology, has led to a diagnostic confusion that has not taken account of their differing developmental trajectories. Such suggestions of a return to the concept of the unitary psychosis arise where association has been mistaken for causation – both may have similar underlying anomalies giving rise to similar, but not identical symptomatology (Box 3).


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Box 4 Forensic presentations
The following criminal behaviours might indicate undiagnosed Asperger syndrome:


Obsessive harassment (stalking)

Inexplicable violence

Computer crime

Offences arising out of misjudged social relationships




Box 5 Characteristic features of Asperger syndrome that predispose to criminal offending

An innate lack of concern for the outcome can result in, for example, an assault that is disproportionately intense and damaging. Individuals often lack insight and deny responsibility, blaming someone else; this may be part of an inability to see their inappropriate behaviour as others see it.

An innate lack of awareness of the outcome that allows individuals to embark on actions with unforeseen consequences; for example, fire-setting may result in a building’s destruction, and assault in death.

Impulsivity, sometimes violent, can be a component of comorbid ADHD or of anxiety turning into panic.

Social naïvety and the misinterpretation of relationships can leave the individual open to exploitation as a stooge. Their limited emotional knowledge can lead to a childish approach to adult situations and relationships, resulting, for example, in the mistaking of social attraction or friendship for love.

Misinterpreting rules, particularly social ones, individuals find themselves unwittingly embroiled in offences such as date rape.

Difficulty in judging the age of others can lead the person into illegal relationships and acts such as sexual advances to somebody under age.

Overriding obsessions can lead to offences such as stalking or compulsive theft. Admonition can increase anxiety and consequently a ruminative thinking of the unthinkable that increases the likelihood of action.

In formal interviews, misjudging relationships and consequences can permit an incautious frankness and the disclosure of private fantasies which, although no more lurid than any adolescent’s, are best not revealed.

Lacking motivation to change, individuals may remain stuck in a risky pattern of behaviour.