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Lenz microphthalmia syndrome is a rare X-linked recessive condition first described by Lenz in 1955 and comprises of anophthalmia, microcephaly, mental retardation, external ear, digital, cardiac, skeletal, and urogenital anomalies. We present three brothers (ages 15 years, 9 years, and 18 months) and a maternal uncle (age 27 years) with congenital anophthalmia, delayed motor development, hypotonia, and moderate to severe mental retardation. They also have abnormally modeled ears, high-arched palate, pectus excavatum, finger and toe syndactyly, clinodactyly, fetal pads, scoliosis, cardiac, and renal abnormalities. An obligate carrier had abnormally modeled ears and syndactyly of the 2nd to 3rd toes bilaterally. Linkage and haplotype analysis in this family indicates that the gene is located in a 17.65-cM region on chromosome region Xq27-Xq28.

Join forces. Advancing clinical medicine to improve health care value and outcomes requires professional translators-competently trained translational scientists who are educated across the diverse spectrum of translational components and capable of effi cient communication with diverse stakeholders across multiple disciplines and areas of expertise required to vet early-stage ideas into products. revealed low internal validity, such as a lack of randomization and blinding or insu% -cient statistical power, as well as low external validity (for example, modeling diseases of elderly humans in young, healthy mice). T ese limitations of en preclude translation of basic f ndings to any kind of relevant clinical application. Post-hoc "prediction" of clinical trial failures might help to improve or innovate preclinical models to be more reliable, reproducible, and predictive.To enhance reproducibility, some journals, including Science Translational Medicine, Science, and Nature (10-12), and funding bodies, such as the U.S. National Institute of Neurological Disorders and Stroke (NINDS) (13), have devised technical study reporting checklists (f g. S1) and publication requirements. Although these requirements are more of en imposed at the manuscript revision stage, their implementation even sooner in the process-for example, at study conception (hypothesis generation and study design)-would better transform the mindset of translational scientists to ensure that preclinical studies are designed to yield higher clinical success rates.Appreciating and discerning that failure is an e% cient mode of drug and target selection is also requisite to improving translation and to providing teaching examples for young researchers. Too frequently, basic academic research lacks the inherent ability to fail early and quickly, as is now the common mindset for product-pipeline development in the pharmaceutical industry. Negative results have few publication venues. On this issue, journals are also working to f ght this publication bias, with certain journals introducing a "negative results section" and other new journals starting only to report signif cant negative results (14). It is not clear yet if these are equalizing solutions or are just another way to segregate negative results. One mechanism for highlighting the importance of negative results may be to publish them alongside positive ones when the negative results illustrate something fundamental and distinct about therapeutics discovery or human pathophysiology (versus simply descriptive results of a failed investigation).Unfortunately, failed studies and negative results of en have no respected place in an academic portfolio. T e tenure and promotion systems do not rate such studies highly, however important they are for accurate reporting and translation. Many indepth mechanistic analyses lack relevance to human biology, but instead ref ect only the experimental context in which they were generated (that is, the lab bench); yet, these studies are viewed more positively than t...

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