BRAT1 Mutation Retrospective Diagnosis: A Case Report.

Biallelic mutations in the BRAT1 gene have been reported in cases with Lethal neonatal rigidity and multifocal seizure syndrome (RMFSL), since 2012. Clinical features include progressive encephalopathy, dysmorphic features, microcephaly, hypertonia, developmental delay, refractory epilepsy, episodic apnea, and bradycardia. More recently, biallelic BRAT1 mutations have been associated with a milder phenotype in patients with migrating focal seizures in the absence of rigidity or with nonprogressive congenital ataxia with or without epilepsy (NEDCAS). It has been proposed that the loss of function caused by BRAT1 mutations may decrease cell proliferation and migration and cause neuronal atrophy through impairment of mitochondrial homeostasis. We here report a female infant with a phenotype, electroencephalogram (EEG), and brain magnetic resonance imaging (MRI) consistent with RMFSL, whose diagnosis was indirectly formulated three years after death upon the identification in both parents of a known pathogenetic variant in the BRAT1 gene. Our report emphasizes the remarkable potential of novel genetic technologies for the diagnosis of past unsolved clinical cases.

Robotic surgery in Hirschsprung disease: a unicentric experience on 31 procedures.

Robotic surgery has been increasingly applied to Hirschsprung patients with encouraging results. We report the results of a 5 year unicentric experience. All consecutive HSCR patients older than 12 months who underwent a surgical procedure with robotic approach between September 2017 and August 2022 were prospectively included. We collected data regarding demographics, extent of aganglionosis, associated anomalies, indications to surgery, and a number of perioperative data such as surgical details, intraoperative and perioperative complications, length of surgery, length of hospital stay, and functional outcome. A total of 28 patients underwent 31 robotic procedures during the study period. Median age at surgery was 82 months. Eleven primary Totally Robotic Soave Pull-Through, 12 redoes, 5 innervative mapping, 2 redundant rectal pouch excision, and 1 Miles' procedures have been performed. Median console time was 145 min. No conversion to either laparoscopy nor to laparotomy was required. Median length of hospital stay was 6 days. Two patients experienced complications requiring reiterative surgery. One patient experienced mild postoperative enterocolitis. Normal continence was achieved by 70% of patients after a median of 16 months postoperatively (80% for primary pull-throughs, 55% for redoes). To conclude, robotic surgery for older HSCR patients proved to be feasible, safe, and effective. Patients with complex surgical requirements seem to benefit most from this promising approach. Provided the economic burden is addressed and solved, robotic surgery will represent an excellent alternative for the surgical treatment of HSCR patients.

Congenital anomalies of the kidney and urinary tract in a cohort of 280 consecutive patients with Hirschsprung disease.

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) have been underestimated in Hirschsprung disease (HSCR). This paper aims at reporting results of patients with HSCR who underwent kidney and urinary tract assessment. METHODS: Patients seen between December 2005 and November 2020 underwent a complete kidney and urinary tract diagnostic workup. Data regarding CAKUT, gender, length of aganglionosis, familial history, HSCR-associated enterocolitis (HAEC), RET genotype, and outcome were collected. RESULTS: Out of 472 patients, 280 completed the workup and represented the focus. Male to female ratio was 3.24:1. Familial cases accounted for 9.8% of patients. RET mutations were detected in 19.8%. We encountered a total of 61 patients with 70 nephrological issues (21.8%), including 28 hypoplasia/dysplasia, 12 hydronephrosis, 11 vesicoureteric reflux, 7 duplex collecting system, 2 kidney agenesis, 2 horseshoe kidney, and 8 miscellanea, involving 91 kidneys without side preponderance (50 right, 41 left). Of these 61 patients, 20 (7.1% of the whole series) required medical or surgical treatment. When comparing patients with and without CAKUT, familial history proved to occur with a significantly lower frequency in the former as did better patient perspectives of outcome. CONCLUSIONS: We confirmed that all diagnostic workups in HSCR should include a complete kidney and urinary tract diagnostic workup. Our study suggests that genes other than RET could play a role in determining CAKUT. Given worse patient perspectives of outcome, CAKUT seems to significantly interfere with quality of life thus confirming the need for early diagnosis and tailored prevention strategies.

Minimally Invasive Redo Pull-Throughs in Hirschsprung Disease.

Introduction: To reoperate a patient with Hirschsprung disease (HSCR) can be technically demanding and most surgeons would resort to conventional laparotomy. This article describes a series of patients with postoperative obstructive symptoms who underwent minimally invasive redo pull-throughs (MIRPT) (either laparoscopic or robotic) to assess the role of minimally invasive surgery (MIS) in complicated HSCR patients. Patients and Methods: All consecutive HSCR patients with postoperative obstructive symptoms, who underwent MIRPT with fast track concepts of care between January 2012 and January 2020, have been included. Data regarding indications, surgical details, complications, and outcome have been compared to those of a series of patients who underwent conventional laparotomic redo. Results: Sixteen patients were included. Male to female ratio was 4.3:1. Median age at surgery was 78 months. Eleven patients underwent laparoscopic redo and 5 underwent robotic redo. Median length of follow-up was 49 months. Reasons for redoing were transition zone pull-through, residual aganglionosis, anastomotic retraction or leak, rectal diverticulum, and refractory anastomotic stricture. No major intraoperative complication occurred. No conversion to laparotomy was required. One patient experienced cuff stricture requiring laparoscopic release. Two patients reported bouts of enterocolitis postoperatively. Compared to classic laparotomic redo pull-throughs (49 patients with complete data), overall complications were significantly less frequent, accounting for 1 and 21 events, respectively (6% versus 43%) (P = .0067). Continence after a median of 21 months postoperatively scored excellent to good in 9 out of 12 patients, who were assessed on this regard (75%), without statistically significant differences. Conclusions: MIRPT proved to be effective and safe in HSCR patients complaining postoperative obstructive symptoms. Robotic surgery could play a crucial. Our study confirms that complicated HSCR cases can be safely managed by means of MIS, applying concepts of fast track care to serve the best for our patients.

Totally robotic soave pull-through procedure for Hirschsprung's disease: lessons learned from 11 consecutive pediatric patients.

INTRODUCTION: Since Hirschsprung's disease (HSCR) already proved to benefit from robotic surgery, we aimed at describing a wider series of patients with this rare disease who were operated on with a robotic approach. PATIENTS AND METHODS: All consecutive HSCR patients who underwent totally robotic soave pull-through (TRSPT), between October 2015 and June 2019, have been included. Ethical Committee approval was obtained. Data regarding clinical features, technical details, complications, hospital stay, and functional outcome have been prospectively collected for each patient. RESULTS: Eleven patients have been included. Mean age at surgery was 29 months. Median length of surgery was 420 min. Median console time was 180 min. Six patients suffered from rectosigmoid aganglionosis, three from long HSCR (extending up to the hepatic flexure), two from total colonic aganglionosis. No major intraoperative complications occurred. Four patients (three of whom carrying a stoma) experienced minor mucosal tearing during dissection. One anastomotic stricture required dilatation under general anesthesia and two cuff strictures required cuff release (both occurring in patients who experienced intraoperative mucosal tearing). Follow-up lasted a median of 12 months. One patient experienced mild postoperative enterocolitis. Continence scored excellent-to-good in all patients who could be assessed on that regard (7 out of 11). CONCLUSIONS: Provided a number of technical key points are respected, the outcome of TRSPT for HSCR is promising. Younger patients, particularly those carrying a stoma, proved to be technically demanding and deserve a longer learning curve. Accurate preoperative bowel preparation, correct trocar placement and patient positioning proved to be crucial aspects of treatment. To conclude, TRSPT is particularly suitable for older HSCR patients, even those requiring a redo, and represents a valid alternative to available surgical option for this delicate subgroup of HSCR patients.