Craig C Teerlink1, Ryan Bernhisel2, Lisa A Cannon-Albright3, Michael D Rollins4. 1. Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT 84108, USA. Electronic address: craig.teerlink@utah.edu. 2. Myriad Genetics, Salt Lake City, UT 84108, USA. Electronic address: shakabra09@gmail.com. 3. Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT 84108, USA; George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, UT 84148, USA. Electronic address: lisa.albright@utah.edu. 4. Division of Pediatric Surgery, Primary Children's Hospital, University of Utah, Salt Lake City, UT 84113, USA. Electronic address: Michael.Rollins@imail2.org.
Abstract
BACKGROUND: Familial recurrence of Hirschsprung disease (HSCR) is well documented, and risk estimates for relatives have been reported from various populations. We describe the familial clustering of HSCR cases using well-established unbiased familial aggregation techniques within the context of a population genealogy. METHODS: Patients included 264 HSCR cases identified using ICD-9 diagnosis coding from the two largest healthcare providers in Utah who also had linked genealogy data. The GIF statistic was used to identify excess familial clustering by comparing average relatedness of cases to matched controls. In addition, relative risks (RRs) of HSCR in relatives of cases were estimated using age-, sex- and birthplace-matched disease rates, and for several diseases frequently associated with HSCR (Down syndrome, multiple endocrine neoplasia IIa, central hypoventilation syndrome, Bardet-Biedl syndrome, ventricular and atrial septal defect). RESULTS: Significant excess relatedness was observed for all HSCRs (p<1e-3). Significant RRs for HSCR were observed for first-, second-, and fourth-degree relatives of cases (RR=12.0, 10.0, and 4.6, respectively). Significant elevated risks of Down syndrome, Bardet-Biedl syndrome, and atrial and ventricular septal defects were observed for HSCR cases. CONCLUSION: This population-based survey of HSCR provides confirmation of a genetic contribution to HSCR disease and presents unbiased risk estimates that may have clinical value in predicting recurrence. LEVEL OF EVIDENCE RATING: Prognosis study, level II.
BACKGROUND: Familial recurrence of Hirschsprung disease (HSCR) is well documented, and risk estimates for relatives have been reported from various populations. We describe the familial clustering of HSCR cases using well-established unbiased familial aggregation techniques within the context of a population genealogy. METHODS:Patients included 264 HSCR cases identified using ICD-9 diagnosis coding from the two largest healthcare providers in Utah who also had linked genealogy data. The GIF statistic was used to identify excess familial clustering by comparing average relatedness of cases to matched controls. In addition, relative risks (RRs) of HSCR in relatives of cases were estimated using age-, sex- and birthplace-matched disease rates, and for several diseases frequently associated with HSCR (Down syndrome, multiple endocrine neoplasia IIa, central hypoventilation syndrome, Bardet-Biedl syndrome, ventricular and atrial septal defect). RESULTS: Significant excess relatedness was observed for all HSCRs (p<1e-3). Significant RRs for HSCR were observed for first-, second-, and fourth-degree relatives of cases (RR=12.0, 10.0, and 4.6, respectively). Significant elevated risks of Down syndrome, Bardet-Biedl syndrome, and atrial and ventricular septal defects were observed for HSCR cases. CONCLUSION: This population-based survey of HSCR provides confirmation of a genetic contribution to HSCR disease and presents unbiased risk estimates that may have clinical value in predicting recurrence. LEVEL OF EVIDENCE RATING: Prognosis study, level II.
Authors: Nikolas H Kazmers; Zhe Yu; Tyler Barker; Tyler Abraham; Robin Romero; Michael J Jurynec Journal: J Hand Surg Am Date: 2019-11-22 Impact factor: 2.230