A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / Purpose: Infants born with Heterotaxy Syndrome (HS) often have intestinal malrotation in addition to severe congenital heart disease (CHD). Given the catastrophic risk of midgut volvulus, where the vascular supply to the gut is cut off causing necrotic bowel and possible future short‐gut syndrome following surgery, an elective Ladd procedure is recommended at the first diagnosis of malrotation. In patients with severe CHD, however, the risk of complications from prophylactic surgery is high, especially in infancy prior to stable cardiac palliation. This study sought to determine whether deferring a Ladd procedure during the first six months of life in infants with CHD is safe by focusing on the incidence of volvulus in the HS population, morbidity of volvulus and morbidity of an elective Ladd procedure. Methods: Medical records of patients with HS and intestinal malrotation at Phoenix Children’s Hospital from 2006‐2011 were reviewed. Stage of heart surgery, severity of heart disease, diagnosis of intestinal malrotation, and timing of Ladd procedure if applicable were recorded. Results: 31 patients with HS and intestinal malrotation were identified. Of the 31, 9 had a Ladd procedure prior to six months of age, 2 for volvulus and the other 7 either electively or for less severe GI symptoms that were not suggestive of volvulus. The other 22 did not have a Ladd procedure prior to six months of age. There was one death (1/22) from a non‐gastrointestinal cause in a patient who had not undergone a Ladd procedure. There were no deaths in the 9 patients who underwent a Ladd procedure (0/9). Conclusions: Given the low overall incidence of volvulus in HS, and with continued vigilance for obstructive symptoms, this study suggests that delaying the Ladd procedure in asymptomatic patients with HS and CHD and intestinal malrotation is safe. Watchful waiting may reduce the incidence of cardiac complications during the Ladd procedure by allowing for stabilizing cardiac surgical palliation prior to elective abdominal surgery.

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第12919号 / 論医博第2094号 / 新制||医||1009(附属図書館) / 32129 / (主査)教授 戸口田 淳也, 教授 妻木 範行, 教授 安達 泰治 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DGAM

Syndromic craniosynostosis is most commonly associated with mutations in Fibroblast Growth Factor Receptor genes (FGFR)-1, 2 and 3. Clinical and animal reports suggest a link between FGFR-associated craniosynostosis and defects in the gastrointestinal tract (GIT). Objective: to determine whether GIT malformations occur more frequently in the craniosynostosis population with a known FGFR mutation when compared to the general population. Methods: A retrospective chart review of patients diagnosed with Crouzon, Pfeiffer or Apert syndromes between 1990 and 2011 was performed at the Hospital for Sick Children in Toronto. Thirty-two charts meeting inclusion criteria were analyzed for any history of GIT abnormalities. Results: Three out of 32 patients had documented intestinal/bowel malrotations while 7 had gastroesophageal reflux disease. All patients had documented FGFR2 mutations, a finding in line with previous studies and published case reports. Conclusions: Results suggest an association between FGFR-associated craniosynostosis and GIT malformations.

Syndromic craniosynostosis is most commonly associated with mutations in Fibroblast Growth Factor Receptor genes (FGFR)-1, 2 and 3. Clinical and animal reports suggest a link between FGFR-associated craniosynostosis and defects in the gastrointestinal tract (GIT). Objective: to determine whether GIT malformations occur more frequently in the craniosynostosis population with a known FGFR mutation when compared to the general population. Methods: A retrospective chart review of patients diagnosed with Crouzon, Pfeiffer or Apert syndromes between 1990 and 2011 was performed at the Hospital for Sick Children in Toronto. Thirty-two charts meeting inclusion criteria were analyzed for any history of GIT abnormalities. Results: Three out of 32 patients had documented intestinal/bowel malrotations while 7 had gastroesophageal reflux disease. All patients had documented FGFR2 mutations, a finding in line with previous studies and published case reports. Conclusions: Results suggest an association between FGFR-associated craniosynostosis and GIT malformations.