Faculty Bibliography

Patients with rare and complex diseases such as congenital adrenal hyperplasia (CAH) often receive fragmented and inadequate care unless efforts are coordinated among providers. Translating the concepts of the medical home and comprehensive health care for individuals with CAH offers many benefits for the affected individuals and their families. This manuscript represents the recommendations of a 1.5 day meeting held in September 2009 to discuss the ideal goals for comprehensive care centers for newborns, infants, children, adolescents, and adults with CAH. Participants included pediatric endocrinologists, internal medicine and reproductive endocrinologists, pediatric urologists, pediatric surgeons, psychologists, and pediatric endocrine nurse educators. One unique aspect of this meeting was the active participation of individuals personally affected by CAH as patients or parents of patients. Representatives of Health Research and Services Administration (HRSA), New York-Mid-Atlantic Consortium for Genetics and Newborn Screening Services (NYMAC), and National Newborn Screening and Genetics Resource Center (NNSGRC) also participated. Thus, this document should serve as a 'roadmap' for the development phases of comprehensive care centers (CCC) for individuals and families affected by CAH

Primary vesicoureteral reflux (pVUR) is one of the most common causes of pediatric kidney failure. Linkage scans suggest that pVUR is genetically heterogeneous with two loci on chromosomes 1p13 and 2q37 under autosomal dominant inheritance. Absence of pVUR in parents of affected individuals raises the possibility of a recessive contribution to pVUR. We performed a genome-wide linkage scan in 12 large families segregating pVUR, comprising 72 affected individuals. To avoid potential misspecification of the trait locus, we performed a parametric linkage analysis using both dominant and recessive models. Analysis under the dominant model yielded no signals across the entire genome. In contrast, we identified a unique linkage peak under the recessive model on chromosome 12p11-q13 (D12S1048), which we confirmed by fine mapping. This interval achieved a peak heterogeneity LOD score of 3.6 with 60% of families linked. This heterogeneity LOD score improved to 4.5 with exclusion of two high-density pedigrees that failed to link across the entire genome. The linkage signal on chromosome 12p11-q13 originated from pedigrees of varying ethnicity, suggesting that recessive inheritance of a high frequency risk allele occurs in pVUR kindreds from many different populations. In conclusion, this study identifies a major new locus for pVUR and suggests that in addition to genetic heterogeneity, recessive contributions should be considered in all pVUR genome scans

Vesicoureteral reflux is a well-recognized cause of childhood illness and renal damage. In the past, surgical reimplantation had been the only procedure available to gain the immediate cessation of reflux. The development of an endoscopic injection technique as a less morbid alternative to traditional surgery began in the 1980s. Teflon was the first injectable agent to be investigated. The record of Teflon is one of efficacy and apparent patient tolerance. However, concerns regarding possible migration and other side effects led to a search for other injectable agents. The most recently investigated agents are polydimethylsiloxane and dextranomer polymer. These agents do not have the long-term follow-up of Teflon, but appear to be effective and safe. Time will tell which agent will become the implant of choice, but it seems clear that endoscopic management will play an increasingly larger role in the care of vesicoureteral reflux.

The understanding of the complex branching morphogenesis of the early kidney is at an early stage; however, a framework is emerging that suggests numerous active genes sequentially switching on and reciprocally influencing each other. Much of our understanding of this process comes from studies of rodents specifically engineered to lack a particular gene responsible for an inductive agent or receptor. This review attempts to place newly discovered genetic programs within an organized framework of sequential renal development.