Case Report: A novel PHOX2B p.Ala248_Ala266dup variant causing congenital central hypoventilation syndrome.

Introduction: Congenital central hypoventilation syndrome (CCHS) is a rare disease characterized by central alveolar hypoventilation and impaired autonomic regulation, caused by pathogenic variants of PHOX2B gene. More than 90% of patients have a polyalanine repeat mutation (PARM) in the heterozygous state, characterized by the expansion of GCN repeats and an increase in the number of alanine repeats, so that genotypes 20/24-20/33 are formed (the normal genotype is 20/20). The remaining 10% of patients harbor non-PARMs. Case description: We present a clinical case of a girl with a novel PHOX2B heterozygous genetic variant in the exon 3: NM_003924.4: c.735_791dup, p.Ala248_Ala266dup. The duplication includes 16 GCN (alanine) repeats and 3 adjacent amino acids. Both clinically healthy parents demonstrated a normal PHOX2B sequence. In addition, the girl has a variant of unknown significance in RYR1 gene and a variant of unknown significance in NKX2-5 gene. The child's phenotype is quite special. She needs ventilation during sleep, and has Hirschsprung's disease type I, arteriovenous malformation S4 of the left lung, ventricular and atrium septal defects, coronary right ventricular fistula, hemodynamically nonsignificant, episodes of sick sinus and atrioventricular dissociation with bradycardia, divergent alternating strabismus, and oculus uterque (both eyes) (OU) retinal angiopathy. Two episodes of hypoglycemic seizures were also registered. Severe pulmonary hypertension resolved after appropriate ventilation adjustment. Diagnostic odyssey was quite dramatic. Conclusion: Detection of a novel PHOX2B variant expands the understanding of molecular mechanisms of CCHS and genotype-phenotype correlations.

Transposition and fixation of lower pole crossing vessel in children with ureteropelvic junction obstruction: A STROBE-compliant study.

ABSTRACT: Chapman and Hellstrom techniques are typically employed to transpose renal lower pole crossing vessels (LPCVs). Both procedures have certain limitations. We investigated the midterm outcomes in pediatric patients in whom LPCV-induced ureteropelvic junction obstruction was treated with either dismembered Anderson-Hynes pyeloplasty or upward transposition coupled with a new technique to fix the LPCV.We retrospectively compared Anderson-Hynes pyeloplasty to the new technique in terms of outcome. LPCV transposition was considered feasible in patients in whom the diuretic loading test revealed a decrease in the pelvic volume after correction of vascular compression as well as absence of structural changes in the ureteropelvic junction (UPJ) and hemodynamic compromise of the lower renal pole. The fascial flap was passed below the LPCV to form a "hammock". The free edge of the flap was sutured to its base.Group 1 consisted of 102 (69.9%) patients (median age: 7.9 years) undergoing dismembered Anderson-Hynes pyeloplasty, while group 2 included 44 (30.1%) patients (median age: 8.4 years) treated with upward transposition and the new technique to fix the LPCV. No intra-operative complications or conversions occurred in either group. Redo-pyeloplasty was performed in 3 (2.9%) children of group 1 and 1 (2.3%) child of group 2. Renal ultrasonography conducted 12 months after surgery revealed similar anteroposterior diameters of the renal pelvis in groups 1 (7.9 ±â€Š8.1 mm) and 2 (6.0 ±â€Š2.9 mm). Patients in both groups showed a non-significant median increase in differential renal function at follow-up after at least 1 year after surgery (group 1: 36% [33.3; 40.5] vs 36.5% [35.3; 41.0]; group 2: 41% [37.5; 46.0] vs 43% [39; 46]).In our patients, the new technique for laparoscopic or open fixation of the obstructing vessel after transposition was effective, reproducible, and devoid of limitations typical for the Chapman and Hellstrom techniques. We recommend Anderson-Hynes pyeloplasty in children with a history of hydronephrosis diagnosed antenatally, recurrent abdominal pain, intra-operative absence of peristalsis across the UPJ, high location of the UPJ at the renal pelvis, or intra-operative absence of volume reduction of the renal pelvis upon furosemide testing.

[Disorders of sex differentiation: state of the problem 15 years after the Chicago consensus].

It is well known that the nomenclature and classification were changed in 2005 at the international consensus conference on intersex disorders, held in Chicago, where, among others, the following recommendations were proposed: (1) all children should be assigned a gender identity, and this should be done as quickly as possible, taking into account the time required for the examination. (2) all infants with congenital adrenal hyperplasia and 46,XX karyotype, including those with pronounced masculinization, must be raised as women. (3) Surgical treatment should be performed early and in cases of feminizing genitoplasty, clitoral reduction should be performed simultaneously with reconstruction of the urogenital sinus (separation of the vagina and urethra). An analysis of contemporary literature shows that all these theories, proposed 15 years ago at the Chicago meeting, failed to stand the test of time. New nomenclature and classification are constantly being revised. Currently, many groups of patients want to abolish the term «sexual maturity disorders.» Recommendations regarding gender reassignment and appropriate early surgical treatment have been completely ignored in some countries. All this was largely facilitated by the confrontational activities of a number of support groups.

Risk factors for obstructive complications after endoscopic correction of vesico-ureteral reflux using polyacrylate polyalcohol copolymer.

Use of polyacrylate-polyalcohol copolymer (PPC) after endoscopic correction (EC) of vesico-ureteral reflux (VUR) is highly effective but is associated with a higher risk of obstructive complications (OC) compared with other implants. We undertook a STROBE compliant retrospective investigation and studied the OC risk factors to increase the practical safety of PPC.Overall, 798 patients (464 [58.1%] girls and 334 [41.9%]) boys) from 5 hospitals in whom PPC was routinely used were evaluated retrospectively. The patients were subdivided into 2 groups. Group I consisted of 754 (94.5%) children (449 [59.5%] girls and 305 [40.5%] boys) without OC. Median age was 41 months [Q1: 18.0; Q3: 81.0]. Group II comprised 44 (5.5%) patients (29 [65.9%] boys and 15 [34.1%] girls) experiencing OC, and their median age was 21.5 months [Q1: 12.0; Q3: 43.0]. Clinical and renal ultrasound examinations were carried out 1 day and 1 month after EC, and then every 6 months after EC. At the follow-up examination approximately 6 months after EC, voiding cysto-urethrography (VCUG) was performed. All patients with OC underwent diuretic renography.OC occurred in 44 (5.5%) of 798 children, in some cases as late as 60 months after endoscopic injection of the bulking agent PPC for correction of VUR. Univariate analysis revealed that younger age (P < .001), higher grade of VUR (P < .001), male gender (P < .001), second injection (P = .003), and EC injection using hydrodistension implantation technique (HIT; P < .001) represented significant risk factors. At multivariate analysis, only male gender (P = .0078), younger age (P = .0044), HIT technique (P < .0001), and second injection (P = .04) represented significant risk factors for the occurrence of OC.We identified young age, male gender, high reflux grade, HIT technique, and second endoscopic injections as factors associated with the risk of OC after EC of VUR using PPC as a bulking agent. Thus, patients who have undergone EC with PPC must be monitored sonographically for occurrence of OC for at least 60 months after the intervention.