When family history falls short v.1 and the Wall Street Journal

Andrew at ThinkGene asks a very valid question.....

When does family history fall short?

I outlined it in my last post but I figure now might be a good time to review one of the instances when family history falls short.....

But first I want to clarify. When I say family history, I mean at least a 3 generation examination performed by a trained healthcare professional.......not a meeting over Thanksgiving Dinner.....

Those four scenarios I mention include

1. Rare chromosomal anomalies that occur in less that 1% of the population
2. Rare monogenic disease
3. Congenital Anomalies
4. Severe Trauma

Today let's focus on Rare Monogenic Disease. Why? In the Wall Street Journal today, there is an article about a man who is stricken with EOAD.....Early Onset Alzheimer's Disease.....

From the article

"Now 51 years old, Mr. Kammerer, like many Alzheimer's patients, had no history of the disease in his family."

This is a common thing I hear about Alzheimer and yes, even early onset Alzheimer Disease....

Why is this important? Well, we have very little in the way of prevention for AD, we have pretty poor therapies as well. So naturally we would like to know what's coming, and avoid or at least plan for the train wreck....

When I was speaking at the American Geriatric Society meeting in CT earlier this year, I went over APOE e4 testing and Early Onset Alzheimer Disease too.....we covered in some broad strokes, but also cleared up a lot of misconception by physicians...

Yes....but first some good Stats:

1. Family History of AD increases risk of AD lifetime by 250-500%.....so if you have a baseline pop risk of 7-10% this would be 25-50% lifetime risk....

2. Genetic testing identifies 40-80% of EOAD, depending on the study you read

3. EOAD is about 5-10% of Alzheimer Disease

4. 60% of those who have EOAD have a family history.....meaning FamHx misses 40%

But for this important caveat......

Although most individuals diagnosed with EOAD have an affected parent, the family history may appear to be negative because of failure to recognize the disorder in family members, early death of the parent before the onset of symptoms, or reduced penetrance.

So do you guys understand why I say a family history should be done by a trained pro? You can miss things like this, especially if you don't ask about ages of death or other causes......

I ask if anyone has died in a car crash when I take family histories.....not many people do that....but it can be a predictor of seizure disorder, sudden cardiac death, Alzheimer disease, stroke....you have to know what to look for......

So what I found most interesting about this story.....the take away point was not there......even if there was no "family history"......where is the story about genetic testing to identify risk in the children.....that would make for a great discussion or follow up......Is it ethical to test children for this risk? The American College of Medical Genetics would say, "No"

So what do you think???

Does Mr Kammerer have no family history? Does he carry a gene mutation? These are Bayesian questions that need to be answered......we know his pretest for having a family history is 60%...... we also know his likelihood of having a mutation in one of the 3 genes for EOAD (PSEN1, PSEN2, BAPP) is approximately 40% (Low end estimate).....

So do you think he should have seen a healthcare professional to offer genetic testing?

I would say yes. This is one of the times when a rudimentary collected family history may fail us, but perhaps a professionally collected one would show something...

So would a SNP testing identify this risk???? Not most of the Chips.....More importantly, do you really want to get those results in your "home office?"

The Sherpa Says: This genetic testing business is confusing. Not exactly what I would say could be sent out into the world without some training wheels......Not to be "paternalistic" but what if this SNP was on the CHIP.....soon we will have really cheap whole genome analysis and IT WILL be on that.....we have to have a serious discussion of how we can create tools to help us.....not replace us....before the public gets hurt.