Autosomal recessive truncating MAB21L1 mutation associated with a syndromic scrotal agenesis.

We report on a boy with a rare malformative association of scrotum agenesis, ophthalmological anomalies, cerebellar malformation, facial dysmorphism and global development delay. The reported patient was carrying a homozygous frameshift in MAB21L1 detected by whole-exome sequencing, considered as the most likely disease-causing variant. Mab21l1 knockout mice present a strikingly similar malformative association of ophthalmological malformations of the anterior chamber and preputial glands hypoplasia. We hypothesize that MAB21L1 haploinsufficiency cause a previously undescribed syndrome with scrotal agenesis, ophthalmological anomalies, facial dysmorphism and gross psychomotor delay as remarkable hallmarks. Four cases from the literature were reported with features suggestive of a similar and recognizable clinical entity. We hypothesize that MAB21L1 should be the culprit gene in these patients.

Untreated growth hormone deficiency with extremely short stature, bone dysplasia, cleft lip--palate and severe mental retardation in a 26-year-old man with a de novo unbalanced translocation t(1;12)(q24;q24).

We report on a 26-year-old patient presenting with extremely short stature (height 72cm, weight 6.5kg, OFC 42.5cm), facial dysmorphism, cleft lip--palate, severe mental retardation and de novo 1q24.2--q25.2 and 12q24.31 interstitial deletion. He was the only child of non-consanguineous parents and his birth length was 43cm. He had severe feeding difficulties and required enteral nutrition until the age of 3 years. Standard cytogenetic analysis showed an apparently balanced de novo translocation t(1;12)(q24;q24). Endocrine studies at 11 years of age for severe growth retardation revealed multiple pituitary hormone deficiency with severe growth hormone deficiency, but the child was untreated because of associated mental retardation. At 26 years of age, he could not walk or speak and had no signs of puberty. Investigations revealed spondylo-epi-metaphyseal dysplasia with severe osteoporosis, enlarged aorta when compared to the patient's size and apparently normal pituitary development. High resolution karyotype showed a 1q24-q25 deletion, and comparative genomic hybridization studies confirmed the 1q interstitial deletion. FISH studies of both breakpoints using PACs and BACs enabled us to further characterize the 1q interstitial deletion (1q24.2-1q25.2) and also revealed a 12q24.31 interstitial microdeletion. This case is compared with previously reported patients with similar deletions, but the untreated pituitary deficiency could also be responsible in part for the severity of the growth deficiency. This observation is of interest for two reasons. First, these deletions could be a clue in the search for a gene responsible for growth hormone deficiency/midline defects. Second, it shows the importance of molecular cytogenetics in the study of de novo apparently balanced translocation with abnormal phenotype.

Transanal coloanal anastomosis for Hirschsprung's disease: comparison between endorectal and perirectal pull-through procedures.

BACKGROUND/PURPOSE: The aim of this study was to compare the results of 2 procedures of transanal pull-through for the management of rectosigmoid Hirschsprung's disease. METHODS: Twenty-one consecutive children with rectal or rectosigmoid Hirschsprung's disease were operated on between November 1999 and April 2003, in two pediatric surgical departments (Dijon and Strasbourg). Twelve children underwent a transanal perirectal pull-through procedure (TPR) and 9 had a transanal endorectal (Soave) pull-through procedure (TER). The collected data in each group included demographic data, length of aganglionosis, age and weight at operation, operating time, duration of hospital stay, incidence of postoperative complications (sepsis, enterocolitis, stricture) and quality of fecal continence on long-term follow-up. RESULTS: No significant differences were observed between the TPR and TER groups with respect to mean age at presentation, length of aganglionosis (rectosigmoid in 10/12 and 8/9 patients respectively), age at operation, with seventeen children operated on before one year of age (mean 3.8 and 3.3 months, respectively) and duration of hospital stay (5.2 vs. 5.3 days), frequency of bowel movements at 3 months postoperatively (1 - 3 per day). Mild differences were observed between TPR and TER groups for gender (ratio M : F 5 : 1 vs. 2 : 1), gestational age at term (39 vs. 37.5 weeks), birth weight (3240 g vs. 2520 g) and operating time (116 min vs. 138 min). No iatrogenic injury of the surrounding pelvic structures occurred during surgery and no blood transfusion was required in either of the groups. A retrorectal pelvic abscess was found in one child of the TPR group. It resolved after an enterostomy had been performed with parenteral antibiotics. Anal dilatation for postoperative anorectal stricture was required in 3 and 2 patients, respectively, for the TPR and TER groups. A mild postoperative enterocolitis developed in one case in the TER group. The average follow-up period was 35.3 months, but ten children still wear diapers, making a functional evaluation difficult. Constipation was noted in 4 and 3 patients, respectively, for the TPR and TER groups. No permanent soiling has been noted at long-term follow-up. CONCLUSION: As an objective assessment of fecal continence could not yet be done for this short series, further follow-up is required. Up to now, no significant difference was observed between these two transanal pull-through procedures.

[Acute appendicitis in children: is there an histo-clinical correlation?]. / Appendicite aiguë de l'enfant: le classique "absence de parallelisme anatomoclinique": un mythe?

Diagnosis of appendicitis in children represents a continuing diagnostic dilemma for emergency room physicians and paediatric surgeons. If unnecessary surgery should be avoided, delayed diagnosis and treatment of appendicitis is responsible for complications. Use of a diagnostic clinical score may improve the management of children with abdominal pain. A prospective evaluation of an appendicitis score is presented here.

Transplantation of hepatocytes in nonhuman primates: a preclinical model for the treatment of hepatic metabolic diseases.

BACKGROUND: The transplantation of isolated hepatocytes in large animals, including nonhuman primates, must be evaluated before clinical trials are performed. However, in the absence of large transgenic animals and large-animal (as opposed to small-animal) models of genetic deficiencies, it is difficult to evaluate the fate of transplanted hepatocytes, their localization, survival, and function within the parenchyma of the host liver. In this work, we aimed to develop a technique for delivering hepatocytes to the liver of a nonhuman primate and to evaluate their localization and functionality in the short term. METHODS: A 20% hepatectomy was performed in 34 cynomolgus monkeys (Macaca fascicularis) and hepatocytes were isolated. Hepatocytes were labeled in vitro with a recombinant retrovirus expressing the beta-galactosidase gene and returned to the liver by infusion through a portal catheter left in place. Liver biopsies were performed 4 and 7 d after transplantation. RESULTS: Twenty-four monkeys underwent surgery to define the necessary technical adjustments and to optimize conditions. Six monkeys died. The whole protocol, including the transplantation of genetically marked hepatocytes and procurement of liver biopsies, was performed in the remaining 10 monkeys. In eight monkeys, transplanted hepatocytes expressing the beta-galactosidase gene were widely distributed in the portal tracts, sinusoids, and hepatocyte plates of the host liver 4 and 7 d after transplantation. CONCLUSIONS: We have developed an experimental nonhuman primate model for the evaluation of hepatocyte transplantation. We demonstrated the engraftment and functioning of transplanted hepatocytes in the host liver 4 and 7 d after transplantation.

Transabdominal amnioinfusion to avoid fetal demise and intestinal damage in fetuses with gastroschisis and severe oligohydramnios.

BACKGROUND/PURPOSE: Despite dramatic improvement in survival rate for neonates with gastroschisis, significant postoperative morbidity and a low mortality rate still occur. Furthermore, even in recent publications, some fetal death has been reported. Does this mean that antenatal diagnosis of gastroschisis is a missed opportunity? In fact, decreased amniotic fluid (AF) volume is observed in some fetuses with gastroschisis. However, oligohydramnios is associated with an increased risk of fetal suffering. When severe oligohydramnios is observed, intrapartum amnioinfusion, to restore AF volume, may help avoid fetal complications. METHODS: Two fetuses with gastroschisis and severe oligohydramnios were treated antenatally with amnioinfusion of saline solution. In one case, fetal heart beat decelerations were observed at 27 weeks' gestation among with the oligohydroamnios and serial transabdominal amnioinfusions were performed. In the second case, severe oligohydramnios was observed at 31, weeks and an amnioinfusion was performed. The 2 babies were delivered at 31 and 34 weeks, respectively. RESULTS: In both cases, exteriorized bowel was nearly normal at birth, and primary closure could be performed. Outcome was favorable, and they were discharged home on day 43 and day 54, respectively. CONCLUSIONS: Because fetuses with gastroschisis and oligohydramnios are part of a particular high-risk group, serial ultrasound examination and computerized fetal heart beat monitoring are necessary during the third trimester. In selected cases of gastroschisis associated with severe oligohydramnios, serial amnioinfusion may be required.

Gastric outlet obstruction by an antral mucosal diaphragm: a case of a congenital anomaly revealed by an acquired disease.

Congenital antral membrane may become symptomatic early in life or late in childhood. A gastric outlet obstruction was revealed in a 14-month-old girl, previously developing well until 3 days ago, by melaena and recurrent non-bilious vomiting, after administration of a non-steroidal anti-inflammatory drug for fever. Plain X-ray performed during the neonatal period was normal. Despite ultrasonography, contrast radiography and endoscopy, the correct diagnosis was made at surgery; the obstruction was due to an inflammatory, thickened membrane with mucosal oedema reducing the central aperture of the diaphragm. This case emphasizes that if antral membrane diaphragm is congenital, the onset of symptoms may result from an additional acquired lesion.

Antenatal detection of a communicating duodenal duplication.

We report a case of a subhepatic cystic mass diagnosed in utero by antenatal ultrasonography (US) at 15 weeks' gestation which subsequently proved to be a communicating duodenal duplication. In this male foetus, the differential diagnosis was choledochal cyst, congenital biliary atresia, foregut duplication or omentum cyst. Neonatal US examination lead to a diagnosis of duodenal duplication, also confirmed by barium gastrointestinal series. He was operated on day 8 and recovered uneventfully. We discuss the accuracy of antenatal US in the diagnosis of such right upper quadrant cystic masses. Now that antenatal findings are becoming increasingly sensitive in the detection of foetal anomalies, and parents need to be informed about the suspected pathology and its prognosis, we tried to determine, in the light of this case and a review of the literature, how antenatal US findings can offer more accuracy in the diagnosis of duodenal duplication.

Esophageal replacement in children by an isoperistaltic gastric tube: a 12-year experience.

The colonic segment is the most frequently used material for replacing the esophagus in children; however, the use of a gastric tube has become a reliable alternative operation. Since 1987, we have used an isoperistaltic gastric tube to replace the esophagus in children, and we present a series of 21 patients. Indications for operation included caustic injury (nine), esophageal atresia (eight), peptic stricture (two), congenital stricture (one), and esophageal duplication (one). There was no death or necrosis of the graft during the early postoperative period. The esophagogastric anastomosis leaked in two cases, but both of them closed spontaneously. A temporary dumping syndrome was encountered in two children. Two patients had strictures of their upper anastomosis responding to dilatations. The two patients who had a pharyngogastric anastomosis developed either intractable stricture or nonfunctioning anastomosis. One of them died 9 months later from aspiration pneumonitis. At follow-up, 16 of 21 patients could accept a normal diet (13 were entirely asymptomatic, and three suffered occasional mild dysphagia). Two patients suffered significant dysphagia (one had a durable dilation of his gastric tube), and three needed a feeding jejunostomy. Acid secretion of the gastric tube was proved in nine cases. Two patients were shown to have cervical Barrett's esophagus above the anastomosis. These findings indicate the need for lifelong endoscopic follow-up for these patients.

In utero allotransplantation of retrovirally transduced fetal hepatocytes in primates: feasibility and short-term follow-up.

In utero allotransplantation of fetal hepatocytes into a preimmune fetus could be used in early treatment of many inherited hepatic metabolic diseases. This study was designed to assess the tolerance to hepatocyte transplantation and to test the feasability and toxicity of such an injection in a primate model. Fetal hepatocytes were obtained from two 120-day-old Macaca mulatta fetuses and cryopreserved. They were thawed, cultured in vitro, and transduced with a recombinant retrovirus expressing beta-galactosidase. Transduction efficiency was 75-85%. Three unrelated fetuses (90, 100, and 104 days old) were each given 1-2 x 10(7) transduced cells via the umbilical vein. This caused vasospasm and severe bradycardia. Two fetuses died in the 48 hours after transplantation; the third survived and was killed at the end of gestation. No evidence of the infused cells was found. Three fetuses (90 days old) were, therefore, given 3-4 10(7) hepatocytes by direct intrahepatic injection. All the fetuses survived without side effect. Donor cells were not apparent from histochemical staining and PCR reactions. There was no evidence of inflammatory reaction. These findings indicate that the protocole could be improved by increasing the number of transplanted cells and using specific hepatic promoters in the retroviral vectors to achieve an effective postnatal chimerism.