5). Finally we may consider poor health care and genetic illiteracy as factors that contribute to genetic risk in families subject to these conditions, since recognition of genetic risk requires an appropriate diagnosis and sufficient knowledge of the genetics of the disorder in the family. Fig. 5 Global distribution according to ancestry of patients and carriers of cystic fibrosis (in blue) and the hemoglobinopathies (sickle cell disease and thalassaemias), (in red); (courtesy of Dr. P. Lakeman, Dept. of Clinical Genetics, VU University Medical Center, Amsterdam, the Netherlands) SCH727965 chemical structure Genetic risk assessment There are two approaches to assess genetic risk. The

first one involves taking a careful medical history of the couple and their family (see the paper by Bennett in this issue), and the second one is through genetic screening (see the paper by Metcalfe in this issue). As I have argued above, a clear-cut pattern of occurrence of a disease in the family is rather rare, so we have to base our medical history taking on other

principles: 1. Every health problem in one of the partners or in a family member, either at present or in the past, may have a genetic basis, unless there are good arguments to refute this possibility. As stated before, the absence of a second patient with the disorder in the family is never a valid argument against a genetic aetiology.   2. Saracatinib mw Inquiring about the presence of a genetic disorder in the family or presenting a list of disorders that might be genetic is a sure way to miss

important risks as knowledge on whether a given disorder is genetic within a family cannot learn more be presumed and since lists of disorders that may be genetic can never be complete enough. Therefore it is recommended to ask for each person in the family individually about his or her present and past health, including whether GBA3 he or she was ever admitted to hospital and for what reason. This questioning can also be done by means of a written questionnaire or an electronic aid.   3. The surest way to detect genetic risk is to obtain a medical diagnosis for each health problem in the family and to check whether this diagnosis is known to point to a genetic risk. This may involve asking the permission of the patient to question his or her physician about the nature of the disorder and to consult someone with expert knowledge on the genetics of the disorder, or even to refer the couple or the patient to such an expert for further workup (see the paper by Read and Donnai in this issue).   4. Since family histories are dynamic, they need to be updated again and again (American College of Obstetricians and Gynecologists Committee on Genetics 2011; Ziogas et al. 2011).   The sad story of Peter S. Peter S. was 10 months old when his parents became aware that the pupil of his left eye appeared pale on pictures made with flashlight (see Fig. 6).