Osteogenesis imperfecta (IPA: ; OI), colloquially known as brittle bone disease, is a group of genetic disorders that all result in bones that break easily. : 85  The range of symptoms—on the skeleton as well as on the bodys other organs—may be mild to severe. : 1512  Symptoms found in various types of OI include whites of the eye (sclerae) that are blue instead, short stature, loose joints, hearing loss, breathing problems and problems with the teeth (dentinogenesis imperfecta). Potentially life-threatening complications, all of which become more common in more severe OI, include: tearing (dissection) of the major arteries, such as the aorta;: 333  pulmonary valve insufficiency secondary to distortion of the ribcage;: 335–341  and basilar invagination. : 106–107 The underlying mechanism is usually a problem with connective tissue due to a lack of, or poorly formed, type I collagen. : 1513  In more than 90% of cases, OI occurs due to mutations in the COL1A1 or COL1A2 genes. These mutations may be inherited from a persons parents in an autosomal dominant manner but may also occur spontaneously (de novo). There are four clinically defined types: type I, the least severe; type IV, moderately severe; type III, severe and progressively deforming; and type II, perinatally lethal. As of September 2021, 19 different genes are known to cause the 21 documented genetically defined types of OI, many of which are extremely rare and have only been documented in a few individuals.
Second-line treatment is the same as for nonseminomas.Stage 3 seminoma is characterized by the presence of metastasis outside the retroperitoneum—the lungs in "good risk" cases or elsewhere in "intermediate risk" cases. This is treated with combination chemotherapy. Second-line treatment follows nonseminoma protocols. References


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