Sunday, March 30, 2008

Basal cell nevus syndrome is an autosomal dominant condition with complete

Basal Cell Nevus Syndrome: Guidelines for Early Detection

GEORGE J. BITAR, M.D., Fairfax, Virginia
CHARLES K. HERMAN, M.D., Albert Einstein College of Medicine, Bronx, New York
MOHAMMED I. DAHMAN, M.D., Ain Shams University, Cairo, Egypt
MARTIN A. HOARD, M.D., University of Virginia, Charlottesville, Virginia

Basal cell nevus syndrome is an autosomal dominant condition with complete penetrance and variable expressivity. It is characterized by five major components, including multiple nevoid basal cell carcinomas, jaw cysts, congenital skeletal abnormalities, ectopic calcifications, and plantar or palmar pits. Other features include a host of benign tumors, ocular defects, and cleft lip and palate. Guidelines for diagnosis include a family history, careful oral and skin examinations, chest and skull radiographs, panoramic radiographs of the jaw, magnetic resonance imaging of the brain, and pelvic ultrasonography in women. (Am Fam Physician 2002;65:2501-4. Copyright© 2002 American Academy of Family Physicians.)
A PDF version of this document is available. Download PDF now (4 pages/ 144 KB). More information on using PDF files.

Basal cell nevus syndrome, also known as Gorlin's syndrome, was first reported by Jarisch and White in 1894. The spectrum of disease associated with this syndrome was described in detail by Gorlin in 1960.1 The prevalence is estimated to be 1 per 60,000 persons.2 This syndrome is characterized by five major components as well as other features that may be present (Table 1).3,4 Basal cell nevus syndrome is an autosomal dominant condition with complete penetrance and variable expressivity.5,6 The gene responsible has been localized to chromosome 9q22.1-q31.7,8


Saturday, March 29, 2008

Paternal Age Increasing Genetic Disorders in Offspring

There are two types of paternal age effects. One relates to the autosomes and the other to the X chromosome. New autosomalmutations for dominant conditions show up in the children. Their diseases are due directly to advanced paternal age.

New mutations on the X chromosome are usually not evident in the children. They are transmitted to daughters who are at risk for having sons with X-linked diseases. This is an indirect paternal age effect; it is the effect of the age of the maternal grandfather.

Examples of autosomal dominant conditions associated with advanced paternal age include achondroplasia, neurofibromatosis, Marfan syndrome, Treacher Collins syndrome, Waardenburg syndrome, thanatophoric dysplasia, osteogenesis imperfecta, and Apert syndrome.

Examples of X-linked conditions associated with increased maternal grandfather's age include fragile X, hemophilia A (factor VIII deficiency), hemophilia B (factor IX deficiency), Duchenne muscular dystrophy, incontinentia pigmenti, Hunter syndrome, Bruton-type agammaglobulinemia, and retinitis pigmentosa.

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Saturday, March 22, 2008

One Third Of Hemophilia is Sporadic

Friday, March 21, 2008

Here are 5 things you didn't know about men by Ross Bonander From Ask

"2- Men have their own biological clock
We do indeed have a biological clock of sorts, although instead of one that stops, ours becomes increasingly unreliable over time.

As men age they lose approximately 1% of testosterone every year. The consequence of this deficit is that sperm production decreases, and those that are produced are of a lower quality. For this reason, the older we get the greater the chances that the children we spawn suffer from conditions such as autism, schizophrenia and Down syndrome, to name a few.

To explain why, fertility experts point to cell division: About every 16 days the cells that create sperm and determine their genetic code go through the process of dividing. By the age of 50 that division has happened hundreds and hundreds of times, and each time it did the genetic code was vulnerable to changes that can augment genetic deterioration, making birth defects increasingly likely."

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Saturday, March 8, 2008

Approximately 50% of affected families have a negative family history;in many of these families, the father is older,

suggesting that advanced paternal age may influence the NF-1 mutation.NF-2 is an autosomal dominant disorder of chromosome 22; however,many patients have a negative family history

Neurofibromatosis is a group of inherited development disorders of the nervous system,muscles,bones,and skin that causes formation of multiple,pedunculated,soft tumors, and cafe-au-lait spots. The most common types are NF-1 (von Recklinghausen disease) and NF-2 (bilateral acoustic neurofibromatosis). About 80,000 Americans are known to have neurofibromatosis; in many others, the disorder is overlooked because symptoms are mild. the prognosis varies; however, spinal or intracranial tumors can shorten the patient's life span.Causes and IncidenceNF-1 is an autosomal dominant disorder of chromosome 17 that occurs in about 1 in 30,000 births. Approximately 50% of affected families have a negative family history;in many of these families, the father is older,suggesting that advanced paternal age may influence the NF-1 mutation.NF-2 is an autosomal dominant disorder of chromosome 22; however,many patients have a negative family history.


Thursday, March 6, 2008

An Article Published by the Executive Editor of the Simons Foundation, Apoorva Mandavill


Father's advanced age feeds autism risk
Helen Pearson
25 February 2008 09:00:00 EST

Children of fathers aged 40 or older are nearly six times morelikely to have autism
Are older fathers more likely to have children with autism? A series of epidemiological studies is giving credence to the idea, suggesting that, with age, sperm may accumulate damage that increases risk in the next generation.
Advancing age of the father is known to be a significant risk factor for schizophrenia1. These studies — along with anecdotal suggestions that fathers of autistic children tend to be older than average — prompted Avi Reichenberg of Mount Sinai School of Medicine, New York, to launch one of the first thorough epidemiological investigations into a link between the two.
Reichenberg and his colleagues had access to a vast database of health information collected from more than 132,000 Israeli adolescents who underwent draft board assessment, including psychiatric screening, before entering the army. The researchers were able to identify those who were diagnosed with autism spectrum disorders (ASD), along with the age of their parents.
Children of fathers in their 30s are about 1.6 times more likely to have ASD than children of fathers below age 30, the study found2. Compared with the youngest group, children of fathers aged 40 or older were nearly six times more likely to have ASD. “It was much stronger than we had thought,” Reichenberg says.
Since then, a handful of other epidemiology studies have backed the autism-paternal age connection. In one of these3, a team led by Lisa Croen of Kaiser Permanente Northern California Division of Research in Oakland, California, mined a health database of more than 130,000 births and found that each decade of paternal or maternal age increased risk of autism spectrum disorder by around 30%.
Paternal age “is still a relatively small contributor,” Croen says, “but when you see something that keeps coming up in different populations and study designs you start thinking there must be something to this.”
The link may be real, but researchers have yet to explain what causes it. Perhaps, says Croen, older parents are simply more attuned to the development of their children and therefore more likely to get a diagnosis. “It could be an artifact,” she says. “We don’t have enough data yet to really rule that out.”
Genetic origins
Another simple explanation is that fathers who themselves have autism or mild social deficits are likely to marry and have children at a later age than other men, and these children inherit factors putting them at high risk of developing the condition themselves.
But Reichenberg says that in his studies he has found no link between traits such as shyness, sensitivity and aloofness in parents and the age at which they have children. “It’s not definitive but the evidence is definitely against such an explanation,” he says.
Many researchers instead favor a genetic origin for the phenomenon. Male germ cells go through multiple rounds of division to manufacture sperm throughout a man’s life and, according to one idea, they may accumulate DNA damage as the molecule is copied again and again.
Sperm produced by older men are more likely to carry genetic defects, and these defects could boost their children’s risk of autism. Female germ cells divide far fewer times.
It is also possible that older sperm are more likely to acquire epigenetic defects: ones that do not change the DNA sequence itself, but that alter the activity of genes due to structural or chemical changes to DNA such as methylation.
These genetic changes arise in the egg or sperm rather than being inherited from the parents. Both concepts fit with the knowledge that the majority of ASD cases have a genetic cause, even though they are also the first in a family.
For precedent, geneticists point to a condition called achondroplasia, a common cause of dwarfism and the textbook example of a genetic condition associated with paternal age. The risk of sperm carrying a single point mutation in the gene for a growth factor receptor is thought to increase with the age of the father.
“It would be overwhelmingly logical,” for something similar to be going on in some cases of autism, says human geneticist Arthur Beaudet at Baylor College of Medicine in Houston, Texas. Perhaps just one or two of the many genes associated with the disorder are susceptible to detrimental point mutations as the germ cells age.
Beaudet says he would like to see genetic and epigenetic analyses of single sperm to see if mutation rates differ in the fathers of autistic children, and between younger and older men. “That would be the approach I’d be enthusiastic about,” he says. Reichenberg says that he is pursuing such studies.
Because there are few clearly defined genes for autism risk, it’s not yet clear where to look for these increased mutation rates. And genome-wide studies looking for differences in the rates of point mutations in many sperm are still too expensive and laborious.
Copy numbers
Last year, molecular studies showed that mutations called copy number variations (CNVs) — genomic chunks that can be deleted or duplicated from one person to the next — appear to be major contributors to sporadic autism.
A group led by Michael Wigler and Jonathan Sebat at the Cold Spring Harbor Laboratory in New York looked for CNVs that were present in autistic individuals, but not in their parents. They found CNVs in 10% of children with sporadic autism, 2% of those with familial autism and 1% of controls4.
This suggests that many more cases of sporadic autism may be attributable to spontaneous mutations — either CNVs or more subtle mutations — than had been realized.
Sebat has not examined whether the frequency of these CNV mutations increases in aging germ cells — but he suspects it might. “We don’t have data one way or the other,” he says, “but it’s a very tantalizing hypothesis.”
Many of the cellular systems that protect DNA from mutation might begin to fail in aging germ cells, so that their mutation rate increases, Sebat suggests. He is planning to test in a larger group of autistic individuals whether the CNV mutations are more common in children of older parents.
Reichenberg and his colleagues are also testing these hypotheses. In one study, they are trying to compare old and young fathers of autistic children, looking for differences in the rate of new mutations and their association to genetic hotspots previously linked to autism.
They are also doing mouse studies to explore whether offspring of older males tend to suffer more behavioral problems that mimic autism.
There remains some debate about whether the mother’s age is as important a risk factor as that of the father, and studies have differed in their findings. A maternal age effect is harder to tease out, partly because women have children within a more limited age range than men: very few over-40 women have children.
In her study, Croen found that maternal age is just as important and says that other studies have lacked the statistical power to tease this out. “Our data show that maternal age is also in the mix,” she says.
The fact that schizophrenia risk also increases with age leads some researchers to wonder whether some of the same genes may contribute to both disorders – and perhaps to other psychiatric conditions as well.
It’s a “feasible hypothesis”, Reichenberg says, “and I believe a worthwhile one to pursue.”
Malaspina D et al. Arch. Gen. Psychiatry 58, 361-367 (2001) PubMed
Reichenberg A. et al. Arch. Gen. Psychiatry 63, 1026-1032 (2006) PubMed
Croen L. et al. Arch. Pediatr. Adolesc. Med. 161, 334-340 (2007) PubMed
Sebat J. et al. Science 316, 445-449 (2007) PubMed
posted by ApoorvaMandavilli
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