The birth of pediatric urology in the United States: From pioneers to subcertification.

INTRODUCTION: Pediatric urology is a subspecialty of urology that emerged from a culture in which children with urological disorders were cared for by general urologists and general pediatric surgeons. The development of pediatric urology as a subspecialty was years in the making, highlighted by individuals who recognized that children with urological conditions were not just "small adults," but required special experience and training. Subspecialization was initiated by persistent visionaries who recognized the need for a trained cadre of experts to provide better care for children. It took the coordinated effort of all subgroups and leaderships in pediatric urology to push these efforts over the goal line. The focus of this review is to highlight certain individuals who played major roles in this vision and to document the efforts of many to coordinate the pathways to sub-specialization. METHODS: The careers of Meredith F. Campbell and Frank B. Bicknell were researched to identify their rationale and roles in developing pediatric urology as a distinct medical specialty in the United States. In addition, the minutes of the meetings of the Pediatric Urology Advisory Council (PUAC) with the American Board of Urology (ABU) were reviewed. The origins of the Society for Pediatric Urology (SPU) and the American Academy of Pediatrics Section of Urology (AAP-SOU) were researched. The contributions of each to the certification of pediatric urology as a distinct subspecialty was delineated. RESULTS: Campbell was Chair of Urology at the New York University (NYU) School of Medicine and wrote prolifically about pediatric urology. He published one of the first practical textbooks in pediatric urology, almost completely self-written, in 1937. Bicknell, a general urologist in Michigan on the faculty at Wayne State University School of Medicine, led the initiative to create the Society for Pediatric Urology (SPU) that first met at the 1951 annual American Urological Association (AUA) meeting in Chicago and included nine attendees. Subsequently, John Lattimer (College of Physicians and Surgeons at Columbia University) organized a well-attended meeting of urologists interested in pediatrics at the 1964 annual AAP meeting in New York City. This led to the formation of the AAP Section on Urology. Integral to the justification for the development of a subspecialty was evidence of a published corpus of content. In addition to published textbooks devoted exclusively to pediatric urology, this was further fulfilled by the AAP Section on Urology Pediatric Supplement to the Journal of Urology, first published in 1986, and later with the Journal of Pediatric Urology in 2005. The SPU and the AAP Section on Urology came together to form the Pediatric Urology Advisory Council (PUAC) in 2000, which worked with the ABU to create subspecialty certification in pediatric urology with an independent exam, first administered in 2008 to 176 applicants. CONCLUSION: The metaphor "We have stood on the shoulders of giants" is apt for pediatric urology: Meredith Campbell, Frank Bicknell, David Innes Williams (Hospital for Sick Children, London), and J. Herbert Johnston (Alder Hay Hospital, Liverpool) come to mind among the first generation of pediatric urology pioneers, and others among their colleagues also had significant impact. Clearly this is a story of persistence and attention to detail on the part of those giants and those who followed. Pediatric urology became a distinct discipline after the SPU and AAP-SOU came together to create a robust cohort of pediatric urologists who through education and negotiation were able to help the ABU and the American Board of Medical Specialties (ABMS) recognize that subspecialization would lead to better care for children with urologic disorders. This benchmark set a high bar for future subspecialization in urology and other fields.

Persistent Mullerian duct syndrome caused by both a 27-bp deletion and a novel splice mutation in the MIS type II receptor gene.

BACKGROUND: Persistent Mullerian duct syndrome (PMDS) is a rare form of male pseudohermaphroditism that is characterized by the persistence of Mullerian derivatives in otherwise normally virilized males. Mutations of the Mullerian inhibiting substance (MIS) gene or the MIS type II receptor (MISRII) gene have been identified in PMDS patients with autosomal recessive transmission. We analyzed a compound heterozygote PMDS patient who had a 27-bp deletion in exon 10 in one allele and a novel mutation in intron 5 in the other allele of the MISRII gene. METHODS: Whole blood and tissue samples were obtained from a one-month-old 46,XY male with persistent PMDS and the MISRII gene was sequenced and compared to his mother's genomic DNA and that of 22 normal individuals. Serum MIS and the reproductive hormones were measured by standard immunoassays. RESULTS: The patient's hormone levels were normal but the gene for MISRII contained several mutations, a 27-bp deletion in exon 10 on one allele (one of the most common mutations in PMDS) and a novel mutation in intron 5 in the other allele that altered splicing, resulting in retention of the intron and a frameshift, introducing a stop codon. Other mutations in introns 6 and 9 and in exon 11 might not be functionally significant. CONCLUSIONS: This case reveals a novel mutation in the MISRII gene involving intronic sequences, which when coexisting with the already identified 27-bp deletion in exon 10, leads to PMDS.