PURPOSE: We sought to identify causative nongenetic and genetic risk factors for the bladder exstrophy-epispadias complex. MATERIALS AND METHODS: A total of 237 families with the bladder exstrophy-epispadias complex were invited to participate in the study, and information was obtained from 214 families, mainly from European countries. RESULTS: Two families showed familial occurrence. Male predominance was found among all subgroups comprising epispadias, classic bladder exstrophy and cloacal exstrophy, with male-to-female ratios of 1.4:1, 2.8:1 and 2.0:1, respectively (p = 0.001). No association with parental age, maternal reproductive history or periconceptional maternal exposure to alcohol, drugs, chemical noxae, radiation or infections was found. However, periconceptional maternal exposure to smoking was significantly more common in patients with cloacal exstrophy than in the combined group of patients with epispadias/classic bladder exstrophy (p = 0.009). Only 16.8% of mothers followed the current recommendations of periconceptional folic acid supplementation, and 17.6% had started supplementation before 10 weeks of gestation. Interestingly, in the latter group mothers of patients with cloacal exstrophy were more compliant with folic acid supplementation than were mothers of the combined group of patients with epispadias/classic bladder exstrophy (p = 0.037). Furthermore, mothers of children with cloacal exstrophy knew significantly more often prenatally that their child would have a congenital malformation than did mothers of children with epispadias/classic bladder exstrophy (p <0.0001). CONCLUSIONS: Our study corroborates the hypothesis that epispadias, classic bladder exstrophy and cloacal exstrophy are causally related, representing a spectrum of the same developmental defect, with a small risk of recurrence within families. Embryonic exposure to maternal smoking appears to enforce the severity, whereas periconceptional folic acid supplementation does not seem to alleviate it. There is a disproportional prenatal ultrasound detection rate between severe and mild phenotypes, possibly due to the neglect of imaging of full bladders with a focus on neural tube defects.
PURPOSE: We sought to identify causative nongenetic and genetic risk factors for the bladder exstrophy-epispadias complex. MATERIALS AND METHODS: A total of 237 families with the bladder exstrophy-epispadias complex were invited to participate in the study, and information was obtained from 214 families, mainly from European countries. RESULTS: Two families showed familial occurrence. Male predominance was found among all subgroups comprising epispadias, classic bladder exstrophy and cloacal exstrophy, with male-to-female ratios of 1.4:1, 2.8:1 and 2.0:1, respectively (p = 0.001). No association with parental age, maternal reproductive history or periconceptional maternal exposure to alcohol, drugs, chemical noxae, radiation or infections was found. However, periconceptional maternal exposure to smoking was significantly more common in patients with cloacal exstrophy than in the combined group of patients with epispadias/classic bladder exstrophy (p = 0.009). Only 16.8% of mothers followed the current recommendations of periconceptional folic acid supplementation, and 17.6% had started supplementation before 10 weeks of gestation. Interestingly, in the latter group mothers of patients with cloacal exstrophy were more compliant with folic acid supplementation than were mothers of the combined group of patients with epispadias/classic bladder exstrophy (p = 0.037). Furthermore, mothers of children with cloacal exstrophy knew significantly more often prenatally that their child would have a congenital malformation than did mothers of children with epispadias/classic bladder exstrophy (p <0.0001). CONCLUSIONS: Our study corroborates the hypothesis that epispadias, classic bladder exstrophy and cloacal exstrophy are causally related, representing a spectrum of the same developmental defect, with a small risk of recurrence within families. Embryonic exposure to maternal smoking appears to enforce the severity, whereas periconceptional folic acid supplementation does not seem to alleviate it. There is a disproportional prenatal ultrasound detection rate between severe and mild phenotypes, possibly due to the neglect of imaging of full bladders with a focus on neural tube defects.
Authors: Heiko Reutter; Lihong Qi; John P Gearhart; Thomas Boemers; Anne-Karoline Ebert; Wolfgang Rösch; Michael Ludwig; Simeon A Boyadjiev Journal: Am J Med Genet A Date: 2007-11-15 Impact factor: 2.802
Authors: N E Maestri; T H Beaty; J Hetmanski; E A Smith; I McIntosh; D F Wyszynski; K Y Liang; D L Duffy; C VanderKolk Journal: Am J Med Genet Date: 1997-12-19
Authors: Csaba Siffel; Adolfo Correa; Emmanuelle Amar; Marian K Bakker; Eva Bermejo-Sánchez; Sebastiano Bianca; Eduardo E Castilla; Maurizio Clementi; Guido Cocchi; Melinda Csáky-Szunyogh; Marcia L Feldkamp; Danielle Landau; Emanuele Leoncini; Zhu Li; R Brian Lowry; Lisa K Marengo; Pierpaolo Mastroiacovo; Margery Morgan; Osvaldo M Mutchinick; Anna Pierini; Anke Rissmann; Annukka Ritvanen; Gioacchino Scarano; Elena Szabova; Richard S Olney Journal: Am J Med Genet C Semin Med Genet Date: 2011-10-14 Impact factor: 3.908
Authors: Heiko Reutter; Markus Draaken; Tracie Pennimpede; Lars Wittler; Felix F Brockschmidt; Anne-Karolin Ebert; Enrika Bartels; Wolfgang Rösch; Thomas M Boemers; Karin Hirsch; Eberhard Schmiedeke; Christian Meesters; Tim Becker; Raimund Stein; Boris Utsch; Elisabeth Mangold; Agneta Nordenskjöld; Gillian Barker; Christina Clementsson Kockum; Nadine Zwink; Gundula Holmdahl; Göran Läckgren; Ekkehart Jenetzky; Wouter F J Feitz; Carlo Marcelis; Charlotte H W Wijers; Iris A L M Van Rooij; John P Gearhart; Bernhard G Herrmann; Michael Ludwig; Simeon A Boyadjiev; Markus M Nöthen; Manuel Mattheisen Journal: Hum Mol Genet Date: 2014-05-22 Impact factor: 6.150
Authors: Heiko Reutter; Simeon A Boyadjiev; Lisa Gambhir; Anne-Karoline Ebert; Wolfgang H Rösch; Raimund Stein; Annette Schröder; Thomas M Boemers; Enrika Bartels; Hannes Vogt; Boris Utsch; Martin Müller; Birte Detlefsen; Nadine Zwink; Sebastian Rogenhofer; Rita Gobet; Goedele M A Beckers; Arend Bökenkamp; Abdol-Mohammad Kajbafzadeh; Enrique Jaureguizar; Markus Draaken; Yegappan Lakshmanan; John P Gearhart; Michael Ludwig; Markus M Nöthen; Ekkehart Jenetzky Journal: J Pediatr Date: 2011-06-16 Impact factor: 4.406
Authors: Kim M Keppler-Noreuil; Kristin M Conway; Dereck Shen; Anthony J Rhoads; John C Carey; Paul A Romitti Journal: Am J Med Genet A Date: 2017-09-28 Impact factor: 2.802
Authors: Marlene Martin; Kristina Rodriguez; Miguel Sánchez-Sauco; Gerardo Zambudio-Carmona; Juan Antonio Ortega-García Journal: J Med Case Rep Date: 2009-03-30