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Unexpected weight loss presents a diagnostic challenge as it is associated with a wide range of benign and serious conditions. Although it is readily associated with malignancy, the risk of cancer in adults with unexpected weight loss presenting to primary care is 2% or less. In male patients aged 60 years or older and in patients with concurrent clinical symptoms, signs and abnormal blood test, the risk of cancer increases. Initial testing should include a history including medication review, physical examination and blood tests. Recommended blood tests include a complete blood count, basic metabolic panel, liver function tests, thyroid function tests, C-reactive protein level, erythrocyte sedimentation rate and lactate dehydrogenase measurement. Imaging and invasive testing may be considered based on initial evaluation. When the initial evaluation is unremarkable, an observation period is recommended for young patients in particular.

Publishing a patient history or case report fulfills an important role in education and scientific research. However, this requires proper privacy protection. The main rule is that it must be nearly impossible to identify a patient in the presented case. If complete anonymity is not a possible, or if this is doubtful, publication is only possible after the patient's informed consent. But what if such authorization cannot be obtained, e.g. after a patient's death, or due to unknown whereabouts? In such a situation it should be possible to publish these cases, but only after careful consideration of all interests by authors and editorial board, possibly including opinions of the next of kin.

Not only rare diseases are uncommon. There are also rare presentations of common diseases, not to mention rare side effects of infrequently prescribed or new drugs. Not all of these rare disease presentations have a genetic causal component. Additional (genetic or non-genetic) ancillary diagnostic tests, in which some of the inevitably occurring chance findings will present us with new problems, are not the solution for this problem, nor are disease or therapy oriented centres of expertise. The solution should be sought in pattern recognition; not by the individual physician, but through collaboration of physicians who take the time to give meaning to carefully obtained clinical parameters in individual patients. The size and composition of such a - often ad hoc - partnership should be adapted to each individual situation.

Whole exome sequencing and whole genome sequencing in undiagnosed disease: of value for certain patient populations Whole exome sequencing and whole genome sequencing (WES/WGS) as a diagnostic tool has become more readily available. A recent study on the diagnostic yield in a highly selected patient population with undiagnosed disease has demonstrated the power of a stringent diagnostic process that includes WES/WGS. Up to one third of patients received a diagnosis, following critical clinical review of tests performed previously, additional targeted biochemical or genetic diagnostic tests and/or the application of WES/WGS. In more than 60% of the resolved cases, WES or WGS played a crucial role. The success of the Undiagnosed Disease Network relies strongly on patient selection, review of clinical symptoms and medical records by a team of specialists, and close collaboration with basic scientists and laboratories to study the clinical impact of possible genetic variations and mutations that are discovered through WES/WGS. Although the results are impressive, it remains to be determined whether such a dedicated approach is feasible in a non-research setting.