Copy number variations in 375 patients with oesophageal atresia and/or tracheoesophageal fistula

Oesophageal atresia (OA) with or without tracheoesophageal fistula (TOF) are rare anatomical congenital malformations whose cause is unknown in over 90% of patients. A genetic background is suggested, and among the reported genetic defects are copy number variations (CNVs). We hypothesized that CNVs contribute to OA/TOF development. Quantifying their prevalence could aid in genetic diagnosis and clinical care strategies. Therefore, we profiled 375 patients in a combined Dutch, American and German cohort via genomic microarray and compared the CNV profiles with their unaffected parents and published control cohorts. We identified 167 rare CNVs containing genes (frequency<0.0005 in our in-house cohort). Eight rare CNVs - in six patients - were de novo, including one CNV previously associated with oesophageal disease. (hg19 chr7:g.(143820444-143839360)-(159119486-159138663)del) 1.55% of isolated OA/TOF patients and 1.62% of patients with additional congenital anomalies had de novo CNVs. Furthermore, three (15q13.3, 16p13.3 and 22q11.2) susceptibility loci were identified based on their overlap with known OA/TOF-associated CNV syndromes and overlap with loci in published CNV association case-control studies in developmental delay. Our study suggests that CNVs contribute to OA/TOF development. In addition to the identified likely deleterious de novo CNVs, we detected 167 rare CNVs. Although not directly disease-causing, these CNVs might be of interest, as they can act as a modifier in a multiple hit model, or as the second hit in a recessive condition

Hand burn injuries in children

A consistently high proportion of thermal injuries in children are to the hand, and scalds and contact burns are the main causes. While most thermal Injuries to the hand in children can be treated conservatively, deep burns can result in scary contractures and syndactylies that cause functional impairments to the hand. Therefore, thermal injuries to the hand in children should be treated in a specialised centre, thus ensuring a differentiated approach with respect to the localisation and extent of the thermal injury. Besides acute therapy, regular follow-up consultations - including splint and compression treatments -, physiotherapy, ergotherapy and, if necessary, corrective surgical measures are of immense importance. Only adherence to this treatment regime can guarantee optimal functional and aesthetic results and minimise daily restrictions for the young patients. The purpose of this article is to illustrate/outline the essential aspects of this treatment of thermal injuries to the infantile hand

An experimental study in six fresh human cadavers using a novel approach to avoid abdominal wall incisions in total colectomy: totally transanal laparoendoscopic single-site pull-through colectomy with J-pouch creation

The use of transanal laparoscopic access to completely avoid abdominal wall incisions represents the most current evolution in minimally invasive surgery. The combination of single-site surgery and natural orifice transluminal endoscopic surgery (NOTES (TM)) can be used for totally transanal laparoendoscopic pull-through colectomy with J-pouch creation (TLPC-J). The aim of the present study was to provide evidence for the feasibility of TLPC-J in adult human cadavers. TLPC-J was performed in six fresh adult human cadavers. The procedure involved endorectal submucosal dissection from 1 cm above the dentate line to a point above the peritoneal reflection, where the rectal muscle was divided circumferentially. The edge of the mucosal cuff was closed distally in order to prevent fecal contamination and the endorectal tube was placed back into the abdomen. A Triport+(TM) or QuadPort+(TM) system was introduced transanally, and it served as a multiport device (MD). Resection of the entire colon, mobilization of the distal ileal segment, and extracorporeal suture of the ileal J-loop were performed via the transanal approach. The J-pouch was created using Endo GIA (TM). After removal of the MD, the J-pouch was sutured to the rectal wall. TLPC-J was performed in all cadavers, with a mean operation duration of 236 +/- A 22 min. Conversion to either transabdominal laparoscopy or laparotomy was not required in any of the cadavers. No bowel perforation or damage to other organs was observed. The use of a curved endoscope greatly facilitated visualization during transanal laparoscopic dissection for partial and total colectomy, making the procedure feasible. All specimens were retrieved through the anus, eliminating the need for additional transabdominal incisions. TLPC-J was technically feasible in adult human cadavers, and abdominal wall incisions were not required. However, clinical studies are needed to determine its feasibility in living adults

Prenatal Diagnosis of Hydro(metro)colpos: A Series of 20 Cases

Background: Hydrocolpos and hydrometrocolpos are rare malformations caused by accumulation of secretion due to congenital obstruction of the vagina. Hydro(metro)colpos may be isolated or can be combined with other malformations as part of a syndromic disorder. We report on a series of 20 cases with hydro(metro) colpos diagnosed prenatally, delineate the differential diagnoses, and illustrate the spectrum of associated malformations. Subjects and Methods: This was a retrospective study involving 20 fetuses with hydro(metro) colpos at two large tertiary referral centers in Germany over an 18-year period (2000-2017). Results: The median diagnosis was made at 30(+4) weeks of gestation, the earliest at 20(+6) weeks, the latest at 37(+2) weeks. All 20 fetuses presented with the typical cystic structure behind the fetal bladder. Additional malformations included urogenital malformations, hexadactyly, and heart defects. Postnatal fol-low-up revealed that hydro(metro)colpos was associated with anorectal malformation in 11/20 fetuses, McKusick-Kaufman syndrome or Bardet-Biedl syndrome in 4/20 fetuses, Mayer-Rokitansky-Kuster-Hauser syndrome in 3/20 fetuses, and Herlyn-Werner-Wunderlich syndrome in 1/20. In 1 fetus pressure from an intraabdominal teratoma resulted in prenatal hydro(metro) colpos. Conclusion: Hydro(metro) colpos is a rare prenatal sonographic feature. Multidisciplinary prenatal counseling should include all potential syndromes that can present with hydro(metro) colpos in the prenatal setting. (c) 2018 S. Karger AG, Base

Isolated bladder exstrophy in prenatal diagnosis

PurposeIsolated classic bladder exstrophy (CBE) is the most common variant of the bladder-exstrophy-epispadias complex (BEEC). The BEEC represents a spectrum ranging from isolated epispadias over CBE to the most severe form, cloacal exstrophy. We report on a series of 12 cases with CBE diagnosed prenatally and illustrate the spectrum of prenatal ultrasound findings with comparison to prior published reports on this entity.MethodsThis was a retrospective study involving 12 fetuses with CBE at two large tertiary referral centers in Germany over a 14-year period (2004-2018).ResultsMedian diagnosis was made with ultrasound in 24+5 (IQR(25,75): 21+2, 29+0) weeks of gestation. All fetuses presented with the pathognomonic findings non-visualization of the fetal bladder and protruding abdominal mass below the umbilical cord insertion. All fetuses showed normal kidney anatomy and normal amniotic fluid throughout pregnancy. Epispadia was visible prenatally on ultrasound in 6/8 male fetuses. 1/12 Parents opted for termination of pregnancy, 11/12 fetuses were live born and received reconstructive surgery.ConclusionsIsolated CBE is an extremely rare prenatal sonographic finding. Prenatal diagnostics should exclude additional malformations within the spectrum of cloacal malformations

CNV analysis in 169 patients with bladder exstrophy-epispadias complex.

19BACKGROUND: The bladder exstrophy-epispadias complex (BEEC) represents the severe end of the congenital uro-rectal malformation spectrum. Initial studies have implicated rare copy number variations (CNVs), including recurrent duplications of chromosomal region 22q11.21, in BEEC etiology. METHODS: To detect further CNVs, array analysis was performed in 169 BEEC patients. Prior to inclusion, 22q11.21 duplications were excluded using multiplex ligation-dependent probe amplification. RESULTS: Following the application of stringent filter criteria, seven rare CNVs were identified: n = 4, not present in 1307 in-house controls; n = 3, frequency of <0.002 in controls. These CNVs ranged from 1 to 6.08 Mb in size. To identify smaller CNVs, relaxed filter criteria used in the detection of previously reported BEEC associated chromosomal regions were applied. This resulted in the identification of six additional rare CNVs: n = 4, not present in 1307 in-house controls; n = 2, frequency <0.0008 in controls. These CNVs ranged from 0.03-0.08 Mb in size. For 10 of these 13 CNVs, confirmation and segregation analyses were performed (5 of maternal origin; 5 of paternal origin). Interestingly, one female with classic bladder extrophy carried a 1.18 Mb duplication of 22q11.1, a chromosomal region that is associated with cat eye syndrome. CONCLUSIONS: A number of rare CNVs were identified in BEEC patients, and these represent candidates for further evaluation. Rare inherited CNVs may constitute modifiers of, or contributors to, multifactorial BEEC phenotypes.openopenvon Lowtzow, C; Hofmann, A; Zhang, R; Marsch, F; Ebert, Ak; Rösch, W; Stein, R; Boemers, Tm; Hirsch, K; Marcelis, C; Feitz, Wf; Brusco, A; Migone, N; Di Grazia, M; Moebus, S; Nöthen, Mm; Reutter, H; Ludwig, M; Draaken, Mvon Lowtzow, C; Hofmann, A; Zhang, R; Marsch, F; Ebert, Ak; Rösch, W; Stein, R; Boemers, Tm; Hirsch, K; Marcelis, C; Feitz, Wf; Brusco, A; Migone, N; DI GRAZIA, Massimo; Moebus, S; Nöthen, Mm; Reutter, H; Ludwig, M; Draaken, M