1. Using Anatomy and Physiology

2. Patient has symptoms and signs. Doctor tests for specific diseases, and hits the books! –Or, Actually… The Web…

3. Online Mendelian Inheritance in Man – database that collects information on diseases and disorders. Can be searched for symptoms and signs to help diagnosis problems. Using the OMIM search we can find genetic causes and gene malfunctions. Often specific genes can influence many systems… and we need to know how to help the patient.

4. Has an unusual set of medical problems. –Premature –Has a large head (macrocephaly) –Seizures –Abnormal eye alignment (stabismus) –Atrial Septal defect –Mom had polyhdroamniosis during pregnancy … As our young patient grows up we notice… –Limited social contact –Enlarged cerebral ventricles –Increased urine output, but low level of salts –Calcium within the kidneys (nephrocalcinosis) –Hyperextensibility

5. Does not fit “neatly” into our normal diagnosis. Time for research. Step one: OMIM –http://www.ncbi.nlm.nih.gov/sites/entrez?db=om imhttp://www.ncbi.nlm.nih.gov/sites/entrez?db=om im Step two: search his symptoms…

6. How many results did we get? If we change our symptoms do our results change? How can we be sure of our diagnosis? The fewer search results the better, but only one or two is very limiting and can lead you the wrong way. Let’s look at our results…

7. SEARCH: macrocephaly AND polyhydramnios AND seizures Results: 8 Options: –POLYHYDRAMNIOS, MEGALENCEPHALY, AND SYMPTOMATIC EPILEPSY –D-BIFUNCTIONAL PROTEIN DEFICIENCY –CARDIOFACIOCUTANEOUS SYNDROME –OSTEOPATHIA STRIATA WITH CRANIAL SCLEROSIS –COSTELLO SYNDROME –PETERS-PLUS SYNDROME –SIMPSON-GOLABI-BEHMEL SYNDROME

8. Many of our possible search results can give us a variety of symptoms, some our patient has and some he does not. Now what? Look at others with the same symptoms… do they have anything in common?

9. Our patient and several other children have the same symptoms. They do not live close enough to have a common environmental cause to the disease. They all have unaffected siblings… So Doc, NOW WHAT?

10. But for what? We know they have the same symptoms… For any type of genetic similarities NOT common to the rest of the population… We look at a Microarray! This cool bio tool looks for areas of homozygosity (both alleles the same) in a person who has the disease, that is NOT present in those who do not…