Children came into the clinic with non-specific symptoms, such as developmental delay and abnormal gait. Their doctors ran all the possible tests, including assessing a child's metabolic function, to no avail--their conditions had no easy explanation. It was not until we did an extensive genome analysis that we found that these patients had mutations in the GEMIN5 gene."Deepa Rajan, M.D., assistant professor of pediatrics, Pitt School of Medicine, neurologist at UPMC Children's Hospital and co-first author of the study. Thalidomide, sold under the brand names Contergan and Thalomid among others, is a medication used to treat a number of cancers (including multiple myeloma), graft-versus-host disease, and a number of skin conditions including complications of leprosy.[3] While it has been used in a number of HIV-associated conditions, such use is associated with increased levels of the virus.[3] It is administered orally.[3]Common side effects include sleepiness, rash, and dizziness.[3] Severe side effects include tumor lysis syndrome, blood clots, and peripheral neuropathy.[4] Use in pregnancy may harm the foetus, including resulting in malformation of the limbs.[3] In males who are taking the medication, contraception is essential if a partner could become pregnant.[4] It is an immunomodulatory medication and works by a number of mechanisms including stimulating T cells and decreasing TNF-α production.[3]Thalidomide was first marketed in 1957 in West Germany, where it was available over the counter.[5][6] When first released, thalidomide was promoted for anxiety, trouble sleeping, "tension", and morning sickness.[6][7] While it was initially thought to be safe in pregnancy, concerns regarding birth defects arose in 1961 and the medication was removed from the market in Europe that year.[6][5] The total number of embryos affected by use during pregnancy is estimated at 10,000, of which about 40% died around the time of birth.[6][3] Those who survived had limb, eye, urinary tract, and heart problems.[5] Its initial entry into the US market was prevented by Frances Kelsey at the FDA.[7] The birth defects caused by thalidomide led to the development of greater drug regulation and monitoring in many countries.[7][5]Thalidomide causes birth defects.[10][9][16] The U.S. Food and Drug Administration (FDA) and other regulatory agencies have approved marketing of the drug only with an auditable risk evaluation and mitigation strategy that ensures that people using the drug are aware of the risks and avoid pregnancy; this applies to both men and women, as the drug can be transmitted in semen.[16]There is a high risk that thalidomide can cause excessive blood clots. There is also a high risk that thalidomide can interfere with formation of various kinds of new blood cells, creating a risk of infection via neutropenia, leukopenia, and lymphopenia, and risks that blood will not clot via thrombocytopenia. There is also a risk of anemia via lack of red blood cells. The drug can also damage nerves, causing peripheral neuropathy that may be irreversible.[10][9]Thalidomide has several cardiovascular adverse effects, including risk of heart attacks, pulmonary hypertension, and changes in heart rhythm including syncope, bradycardia, and atrioventricular block.[10][9]It can cause liver damage and severe skin reactions like Stevens–Johnson syndrome. It tends to make people sleepy, which creates risk when driving and operating other machinery. As it kills cancer cells, it can cause tumor lysis syndrome. Thalidomide can prevent menstruation.[10][9]Other than the above, very common (reported in more than 10% of people) adverse effects include tremor, dizziness, tingling, numbness, constipation, and peripheral edema.[10][9]Common adverse effects (reported by 1–10% of people) include confusion, depressed mood, reduced coordination, heart failure, difficulty breathing, interstitial lung disease, lung inflammation, vomiting, dry mouth, rashes, dry skin, fever, weakness, and a sense of unwellness.[10][9]There are no expected pharmacokinetic interactions between thalidomide and other medicines due to its neutral effects on P-glycoprotein and the cytochrome P450 family.