Stankiewicz-Isidor syndrome: expanding the clinical and molecular phenotype.

PURPOSE: Haploinsufficiency of PSMD12 has been reported in individuals with neurodevelopmental phenotypes, including developmental delay/intellectual disability (DD/ID), facial dysmorphism, and congenital malformations, defined as Stankiewicz-Isidor syndrome (STISS). Investigations showed that pathogenic variants in PSMD12 perturb intracellular protein homeostasis. Our objective was to further explore the clinical and molecular phenotypic spectrum of STISS. METHODS: We report 24 additional unrelated patients with STISS with various truncating single nucleotide variants or copy-number variant deletions involving PSMD12. We explore disease etiology by assessing patient cells and CRISPR/Cas9-engineered cell clones for various cellular pathways and inflammatory status. RESULTS: The expressivity of most clinical features in STISS is highly variable. In addition to previously reported DD/ID, speech delay, cardiac and renal anomalies, we also confirmed preaxial hand abnormalities as a feature of this syndrome. Of note, 2 patients also showed chilblains resembling signs observed in interferonopathy. Remarkably, our data show that STISS patient cells exhibit a profound remodeling of the mTORC1 and mitophagy pathways with an induction of type I interferon-stimulated genes. CONCLUSION: We refine the phenotype of STISS and show that it can be clinically recognizable and biochemically diagnosed by a type I interferon gene signature.

Postoperative JJ stent is not necessary after balloon high-pressure endoscopic dilatation of primary obstructive megaureter.

INTRODUCTION: A wide range of surgical interventions have been described for the management of primary obstructive megaureter (POM). Endoscopic balloon dilatation has been developed through last decades as a minimally invasive alternative to classic surgery. OBJECTIVE: To assess the need for placement of a double J stent after endoscopic balloon dilatation procedure, by comparing the post-operative related outcomes with and without double J placement. Secondary outcome was the success rate, considering the need for further procedure after endoscopic balloon dilatation and the improvement of the ureteral diameter in the two groups. STUDY DESIGN: Historical retrospective comparison of children treated by endoscopic dilatation for POM, with post-operative JJ stent left in place (2012-2014) or without ureteral JJ stent (since 2015). Post-operative complications were reported following Clavien-Dindo grading system and compared between the two groups. Success rate was defined as absence of need for further surgical reimplantation. Ureteral diameters on preoperative and postoperative renal ultrasounds were compared. RESULTS: Endoscopic dilatations were performed in 42 patients for 46 renal units during the study period. There was a significantly higher rate of post-operative complications in the group with JJ stenting compared to the group without double J stenting regarding all Clavien-Dindo grades (56% vs 15%, p = 0.014) and Clavien-Dindo grade III only (31% vs 0%, p = 0,0051) (Figure). The success rate was similar in the JJ group (75%, F-up: 70 months [13-101]) and the no JJ group (81%, F-up: 26 months [12-95]). There was a significant improvement of US renal pelvis and ureter dilatation in both groups, with a median follow-up of 35.5 months [12-101]. DISCUSSION: The overall rate of complications was slightly higher than in other reports and higher in the JJ group regarding Clavien-Dindo grade III complications. The success rate was comparable to previous studies reviewing endoscopic dilatations and equivalent in the two groups. CONCLUSION: In our study, the omission of postoperative ureteral drainage by a JJ stent after endoscopic balloon dilatation of POM did not increase post-operative complications rate without demonstrable impact on the success rate.

Cutaneous lipoma in children: 5 cases with Bannayan-Riley-Ruvalcaba syndrome.

Cutaneous lipoma is rare in children, but it can be part of a syndrome such as the Bannayan-Riley-Ruvalcaba syndrome (BRRS). The BRRS is a dominant autosomal disorder characterized by cutaneous lipomas, macrocephaly, intestinal polyps, and developmental delay associated with PTEN gene mutations. This syndrome is thought to represent a pediatric form of the Cowden syndrome, characterized among other features by an increased risk of cancer. We report 5 cases of BRRS, all diagnosed in children with lipoma and macrocephaly. Children presenting with lipomas need a complete physical examination to look for other signs of BRRS, because they may need further follow-up for tumor screening in adulthood.

Unstented tubularized incised plate urethroplasty combined with foreskin reconstruction for distal hypospadias.

BACKGROUND AND AIM: Urethral stent has recently been proven to be unnecessary for normal healing in an animal model of tubularized incised plate (TIP) urethroplasty. We report our experience with unstented TIP repair combined with foreskin reconstruction for distal hypospadias in children. PATIENTS AND METHODS: We retrospectively reviewed the records of 162 children consecutively treated by TIP urethroplasty for a distal or mid-shaft hypospadias without urethral stent over a 6 years period. The mean age +/- SEM at surgery was 15.7 +/- 1.2 months. A foreskin reconstruction was performed with the hypospadias repair in 136 boys (84%). One hundred thirty one children (81%) underwent this surgery as an outpatient procedure. RESULTS: With a mean follow-up of 12.4 +/- 1.0 months, urethrocutaneous fistula was observed in 9 children (5.6%), and meatal stenosis in 4 (2.5%). Postoperative urinary retention requiring suprapubic catheter insertion was observed in 4 cases (2.5%) without later complications. Cutaneous dehiscence of the reconstructed foreskin occurred in 6 children (4.4%) and phimosis in 13 (9.5%). CONCLUSIONS: Absence of urethral stent after TIP urethroplasty for distal hypospadias repair does not seem to increase postoperative complication rate. Foreskin reconstruction in distal hypospadias surgery has an acceptable complication rate.