A novel GRK2 variant in a patient with Jeune asphyxiating thoracic dysplasia accompanied by Morgagni hernia.

Skeletal ciliopathies constitute a subgroup of ciliopathies characterized by various skeletal anomalies arising from mutations in genes impacting cilia, ciliogenesis, intraflagellar transport process, or various signaling pathways. Short-rib thoracic dysplasias, previously known as Jeune asphyxiating thoracic dysplasia (ATD), stand out as the most prevalent and prototypical form of skeletal ciliopathies, often associated with semilethality. Recently, pathogenic variants in GRK2, a subfamily of mammalian G protein-coupled receptor kinases, have been identified as one of the underlying causes of Jeune ATD. In this study, we report a new patient with Jeune ATD, in whom exome sequencing revealed a novel homozygous GRK2 variant, and we review the clinical features and radiographic findings. In addition, our findings introduce Morgagni hernia and an organoaxial-type rotation anomaly of the stomach and midgut malrotation for the first time in the context of this recently characterized GRK2-related skeletal ciliopathy.

The Effect of COVID-19 Pandemic on Foreign Body Aspiration.

BACKGROUND: This article evaluates the effect of coronavirus disease 2019 (COVID-19) pandemic on clinical course and management of cases that underwent bronchoscopy for suspected foreign body aspiration (FBA) in children. METHODS: The patients who underwent bronchoscopy with a presumptive diagnosis of FBA between July 2018 and December 2021 were evaluated for demographic features, clinical findings, management details, and outcomes. Patients were divided in two groups: before pandemic (group A) and during pandemic (group B). RESULTS: In total 79 cases with a median age of 5 years (4-5) in group A (n = 47) and 3 years (2-3) in group B (n = 32) were included (p < 0.05). The witnessed aspiration was significantly higher in group B (90.6%) when compared to group A (53%) (p < 0.05). Admission time was less than 48 hours in 30 cases (64%) in group A and 23 cases (72%) in group B (p = 0.002). The intervention time was less than 24 hours in 30 cases (64%) in group A, 9 cases (28%) in group B (p = 0.002). Bronchoscopy was performed after COVID-19 polymerase chain reaction (PCR) testing in all cases in group B. The positive FBA rate was 38% (n = 18) in group A, and 59% (n = 19) in group B (p = 0.067). CONCLUSION: During pandemics, bronchoscopy for FBA was performed in younger infants than before pandemic and witnessed aspiration was significantly more common in that period. The differences in age groups and symptoms may be explained by spending more time at home during pandemics. Waiting for the PCR test results causes delays in the intervention. However, this delay did not cause any respiratory distress.

The Role of Bolus Residue and Its Relation with Respiratory Problems in Children with Esophageal Atresia.

Bolus residue is significant risk factor for postswallow aspiration. A retrospective study was performed to evaluate the role of bolus residue and its relation with respiratory problems in children with esophageal atresia. Children were evaluated for demographic features, type of esophageal atresia, associated anomalies, and respiratory problems. The videofluoroscopic swallowing evaluation (VFSE) was performed, and scored by using the penetration aspiration scale (PAS), bolus residual score (BRS) and normalized residual ratio scale (NRRS). Children with and without respiratory problems were also compared in terms of aspiration and bolus residue. Forty-one children with a median age of 15 months (1-138 months), male:female ratio of 26:15 was included. 65.9% (n = 27) of children were type-C and 24.4% (n = 10) were type-A EA. In 61% (n = 25) of children had liquid aspiration (PAS ≥ 6) and 9.8% (n = 4) had aspiration in pudding consistencies. Children with aspiration in liquids had significantly higher NRRS and BRS scores in vallecular residue for pudding consistencies when compared to children without aspiration (p < 0.05). No difference was detected in terms of PAS scores and bolus residual parameters between children with and without respiratory problems (p > 0.05). Children with aspiration in liquids have higher scores of BRS and NRRS at the level of vallecular especially in pudding consistencies. VFSE findings for bolus residue did not show significant relation with respiratory problems. Respiratory morbidity in children with EA is multifactorial and may not only explained by bolus residuals and aspiration.

The Role of Oral Feeding Time and Sham Feeding on Oropharyngeal Swallowing Functions in Children with Esophageal Atresia.

A retrospective study was performed to evaluate the role of oral feeding (OF) time and sham feeding (SF) on oral-pharyngeal swallowing functions in children with esophageal atresia (EA). Patients with EA were evaluated for age, sex, and types of atresia, time to start OF and surgical complications. Three to six weeks after full OF, videofluoroscopic swallowing evaluation (VFSE) was performed, and Penetration Aspiration Score (PAS, no aspiration = 1, penetration = 2-5, aspiration = 6-8), delay in swallowing reflex and residue after liquid and pudding consistency were noted. Patients were divided into three groups according to repair time; early primary repair (EPR, < 1 month of age), delayed primary repair (DPR, ≥ 1 month of age) and colonic interposition (CI). VFSE findings were compared between groups. In CI group, patients without aspiration in VFSE were encouraged to sham SF before CI. Patients with and without SF in CI group were also compared for oro-pharyngeal dysphagia (OPD). PAS scores were significantly higher in DPR (n = 13) group when compared to CI group (n = 12) in liquid swallowing (p = 0.032) and higher than EPR (n = 30) in pudding consistency (p = 0.03). Patients with CI showed significant OPD when compared to EPR (p = 0.017). Swallowing reflex delay was similar in both groups (p > 0.05). DPR group had significantly higher liquid residue at the level of vallecula (p = 0.028). The residue at other levels (oral, tongue base, pharyngeal wall and pyriform sinus) were similar in all groups in both liquid and pudding consistencies. There was no significant difference between sham-fed (n = 6) and not sham-fed (n = 6) infants in VFSE of OPD (p > 0.05). Patients with DPR without SF had significantly higher incidence of OPD and PAS scores when compared to EPR and CI. Although CI groups has the latest OF time, SF may improve oral motor abilities and cause better OF swallowing functions than patients with delayed repair.

The role of distance between upper and lower esophageal pouches to predict the possibility of delayed repair in children with isolated esophageal atresia.

AIM: A retrospective study was performed to evaluate the role of distance between upper and lower esophageal pouches and pouch lengths to predict delayed primary repair (DPR) in patients with isolated esophageal atresia (EA). METHODS: Patients with isolated EA were evaluated for demographic features, associated anomalies, surgical options, and complications. The babygrams obtained for evaluating gap assessment were examined for the distance between pouches and pouch lengths. Patients were divided into two groups: DPR and esophageal replacement (ER). RESULTS: Fourteen cases with a mean age of 4.1 ± 1.9 years (1-9 years) were included. Female to male ratio was 6:8. There was no significant difference between DPR and ER groups for pouch lengths. The median distance between two pouches were significantly higher in ER group [50 mm (29.4-83.6) vs 18.8 mm (3.4-34.5) (p < 0.05)]. The distance between two pouches and pouch lengths were similar in patients with and without anastomotic strictures (p > 0.05). CONCLUSION: Both upper and lower pouch lengths were shorter in ER group compared to DPR group. However, pouch lengths cannot be considered as a single criterion to predict the need for ER. Large cohort of patients are needed to define the cut-off values for shortest pouch length to achieve a DPR.

Effect of prostaglandin-E1 treatment on pyloric wall thickness in newborns with ductal-dependent critical congenital heart diseases.

BACKGROUND: Prostaglandin E1 (PGE1) is used in the medical treatment of ductal-dependent critical congenital heart disease (CCHD) in neonates. Apnea/bradycardia, hypotension, hypokalemia, and fever are the most important side effects of PGE1. Moreover, gastric outlet obstruction has been reported in a few case reports. A prospective study was conducted to investigate the effect of PGE1 treatment on pyloric wall thickness in newborns with congenital heart diseases. METHODS: A total of 22 newborns with ductal-dependent CCHD having PGE1 infusion longer than a week were included in this study. Ultrasonographic measurements were performed before and one week after the PGE1 infusion to evaluate the pyloric thickness and length. The protocol was registered with ClinicalTrials.govidentifier NCT04496050. RESULTS: A total of 22 neonates with mean gestational age 38 ± 1.8 weeks and birth weight 3105 ± 611 gr were enrolled in the study. The median time of the second ultrasound was seven days. The median cumulative dose of PGE1 given during this period was 108 mcg/kg/min. There was a statistically significant increase in post-treatment pyloric thickness and length compared to pre-treatment measurements (p < 0.001, p < 0.001). None of the patients with increased thickness and pyloric muscle length presented any symptoms. CONCLUSION: PGE1 treatment significantly increased the pyloric thickness and length after at least one-week treatment. PGE1 with its action mechanism is likely to cause gastric outlet obstruction, although not exactly pyloric stenosis on the condition used for a long time.

Management of acute abdomen during the active disease course of COVID-19 and multisystem inflammatory syndrome in children.

PURPOSE: To evaluate the management of children with severe gastrointestinal symptoms during the disease course of COVID-19 and multisystem inflammatory syndrome (MIS-C). METHODS: After ethical approval, we reviewed the medical records, retrospectively, of children with COVID-19 or MIS-C requiring surgical consultation for severe gastrointestinal symptoms. RESULTS: The subjects comprised 15 children, 13 with MIS-C and 2 with COVID-19. Twelve children (80%) had been in known close contact with a person with SARS-CoV-19 and 13 were positive for Anti-SARS-CoV-2 IgG. All the children had experienced fever for at least 1 day and had signs of involvement of two or more systems. Three patients required surgical intervention: one underwent surgical exploration with a presumptive diagnosis of acute appendicitis in the referring center and was transported to our center following clinical deterioration, where a diagnosis of MIS-C was confirmed; and the remaining two developed appendicitis during hospitalization for COVID-19. All three patients had a longer duration of abdominal pain, a higher number of lymphocytes, and a lower level of inflammatory markers than the non-surgically managed patients. None of the patients presenting with MIS-C underwent surgical exploration. CONCLUSION: Gastrointestinal involvement may mimic acute abdomen in children with COVID-19. Thus, children presenting with acute abdomen in the pandemic era require careful evaluation and prompt diagnosis to avoid unnecessary surgical intervention.

Environmental exposure in the etiology of infantile hypertrophic pyloric stenosis: a systematic review and meta-analysis.

PURPOSE: To investigate the occupational and environmental factors in the etiology of infantile hypertrophic pyloric stenosis (IHPS). METHODS: Protocol was drafted according to the PRISMA guidelines and registered on PROSPERO (CRD42020152460). A search for a combination of terms related to IHPS, fetus and neonates, and environmental exposure was performed for studies published between 2000 and 2020 in the EMBASE, Pubmed, and MEDLINE databases. RESULTS: Overall, 2203 abstracts were identified and 829 were screened. The full text of the selected articles (N = 98) was assessed for eligibility. Fifteen studies were included in quantitative synthesis. IHPS risk was significantly lower in black and Hispanic mothers than in white mothers [OR 0.47 (95% CI 0.44-0.51, p < 0.001), OR 0.85 (95% CI 0.77-0.94, p = 0.002), respectively]. Lower maternal education level and maternal smoking were risk factor for IHPS. We further observed a non-significant association between maternal folic acid usage and IHPS risk. Data were insufficient to evaluate occupational exposure. CONCLUSION: This review provides an understanding of the role of environmental exposures in IHPS etiology. Lower maternal educational level, maternal smoking, and white ethnicity are associated with a significantly increased risk of IHPS, while folic acid use seems non-significantly associated with IHPS risk. LEVEL OF EVIDENCE: III.

The cause of dysphagia in patients with esophageal atresia: a systematic review and meta-analysis.

PURPOSE: Dysphagia is the most common symptom in patients with esophageal atresia (EA) of all ages. There is no study addressing the direct relation between dysphagia and surgical results. Therefore, a systematic review was performed to define the relationship between surgical complications and dysphagia in patients with EA. METHODS: The systematic review was drafted under PRISMA guidelines. Systematic literature search was performed for the period 2000 (Jan) to 2019 (Dec)-20 years-in the databases: MEDLINE, EMBASE, and PubMed. Statistical analysis was performed using Comprehensive Meta-Analysis Version 3.0 software. RESULTS: Among 767 articles, 486 abstracts were screened for the inclusion criteria. The full-texts of 64 articles were assessed for eligibility. The sub-group analysis could be performed in 4 articles for anastomotic strictures. Heterogeneity was calculated by I2 statistic as 18,487 and pooled odds ratio was measured under the fixed effect model (Q = 3.68; P = 0.298, I2 = 18,487). There was no significant relationship with an odds ratio of 1.37 between anastomotic stricture (AS) and dysphagia (95% CI 0.631-2.973, p = 0.426). There was no publication bias for the data (Begg's test, p = 0.496; Egger's tests, p = 0.335). CONCLUSION: This meta-analysis did not reveal a significant relationship between AS and dysphagia in children with EA. Since many other factors contribute to dysphagia, comprehensive variable information such as detailed standardized registry systems for rare diseases for pooling analysis is needed regarding other potential factors including surgical complications.

Biallelic ITGB4 variants in familial pyloric atresia without epidermolysis bullosa: Report of two families with five siblings.

Pyloric atresia (PA) is a rare gastrointestinal anomaly that occurs either as an isolated lesion or in association with other congenital or hereditary anomalies. Familial occurrence of PA with epidermolysis bullosa (EB) has been well documented and variants in ITGA6, ITGB4, and PLEC are known to cause EB with PA. However, no gene variants have been defined in familial isolated PA. Five siblings with familial isolated PA are presented that suggest biallelic ITGB4 variants may underlie the development of PA without EB. Five siblings from two unrelated families with isolated PA were studied with exome sequencing (ES) to identify the genetic etiology in isolated familial cases. Exome sequencing was performed in one affected patient from each family. Validation and segregation studies were done by Sanger sequencing. Parents were first cousins in one family but there was no consanguinity in the other family. Type-2 PA was detected in both families and none of the probands had associated anomalies. All patients underwent successful gastroduodenostomy and have been under follow-up uneventfully. All patients had biallelic ITGB4 variants, c.2032G > T p.(Asp678Tyr) being a novel one. Biallelic ITGB4 variants may underlie the development of PA without associated EB. Further detection of variants in this gene may establish any possible genotype-phenotype correlations.

Dysphagia in Children with EA-TEF From the Perspective of Pediatric Surgeons in Clinical Settings.

The current study was aimed to define clinical practice, knowledge and awareness, and best practice regarding dysphagia in children with esophageal atresia with/without tracheoesophageal fistula (EA-TEF) from the perspective of pediatric surgeons in Turkey. Pediatric surgeons practice EA repair were included. A survey related to clinical practice, knowledge and awareness, and best practice regarding dysphagia in EA-TEF was used. The survey was electronically sent to potential participants. Seventy-two pediatric surgeons with a mean professional experience of 14.73 ± 9.66 years (min = 1, max = 41) completed the survey. 19.4% (n = 14) had a standardized protocol for dysphagia screening and %51.4 (n = 37) provided swallowing rehabilitation to their patients. Most of the participants (80.6%) reported that they do not have an appropriate team approach for dysphagia management. The mean knowledge and awareness score was 11.04 ± 1.27 (min = 7, max = 12). The mean VAS score related to the need for standardized protocol in dysphagia management was 9.23 ± 1.44 (min = 3, max = 10). The mean VAS score related to the need for routine screening for dysphagia after surgery was 8.67 ± 2.17 (min = 1, max = 10). The mean score for the degree of the contribution of diagnosis and management of dysphagia to the surgical treatment in children operated for EA-TEF was 7.98 ± 2.08 (min = 3, max = 10). The participants mostly suggested the necessity of a standardized protocol in dysphagia and routine dysphagia screening in children with EA-TEF. Knowledge and awareness is found to be high among pediatric surgeons in Turkey. However, their clinical practice does not include a standardized protocol regarding dysphagia screening and management.

Assessment of the Concerns of Caregivers of Children with Repaired Esophageal Atresia-Tracheoesophageal Fistula Related to Feeding-Swallowing Difficulties.

The study aimed to assess concerns of caregivers of children with EA-TEF related to feeding-swallowing difficulties, compare the concerns according to type of atresia and repair time, and investigate its relationship with time to start oral feeding. Caregivers accompanying 64 children with EA-TEF were included. Age, sex, type of atresia, repair time, and time to start oral feeding were noted. Parents completed the Turkish version of the Feeding/Swallowing Impact Survey (T-FS-IS) to assess the concerns of caregivers related to feeding-swallowing difficulties. The T-FS-IS has three subscales including daily activities, worry, and feeding difficulties. The median age of patients was 3 (min = 1, max = 12) years, of which 57.8% were male. 43.8% of cases were isolated-EA, and 56.3% were EA-distal TEF. 57.8% of cases received early repair, and 42.2% had delayed repair. The median time to start oral feeding was 4 weeks (min = 1, max = 128). The mean scores of daily activities, worry, feeding difficulties, and total score from the T-FS-IS were 2.43 ± 1.18, 2.73 ± 1.28, 2.10 ± 0.97, and 2.44 ± 1.09, respectively. Caregivers of children with isolated-EA reported more problems in total score and all subscales of the T-FS-IS than EA-distal TEF (p < 0.01). Caregivers of children who received delayed repair reported more problems in total score and all subscales of the T-FS-IS than children with early repair (p < 0.05). Moderate to strong correlations were found between the T-FS-IS and time to start oral feeding (p < 0.01, r = 0.55-0.65). This study suggests that caregivers of children with isolated-EA and/or delayed repair and/or delay in oral intake may have higher concerns related to feeding-swallowing difficulties.

Prevention and management of complications in various antegrade enema procedures in children: a review of the literature.

The antegrade continence enema (ACE) procedures are successful surgical options to achieve bowel cleaning in children with faecal incontinence due to a neuropathy or an anorectal malformation and an intractable constipation. The reversed and orthotopic appendicocecostomy, tubularized ileal conduit and the tubularized cecal flap are frequently applied procedures in the treatment of faecal incontinence (FI). The most common complications are the stoma stenosis, leakage, prolapse, adhesive obstruction and the difficulty in catheterization. Each procedure has its own advantages and disadvantages with different complication rates. The postoperative complications of ACE procedures may reduce patient compliance and quality of life. Most of these complications can be preventable and are easy to manage. This review aimed to discuss the prevention and management strategies for various ACE procedure complications.

Polypoid disease of colon in children.

Polyps in gastrointestinal tract are mostly benign and result from hamartomas or lymphoid hyperplasia of submucosa. They usually occur as isolated lesions in children and are referred to as juvenile polyps. Multiple polyps with inherited origin are called polyposis and can be seen as a part of the syndrome. The polyps with adenomatous histopathology have malignant potential and necessitate genetic testing and colonoscopy to define the risk of cancer. Although simple endoscopic removal is adequate in the treatment of juvenile polyps, children with familial adenomatous polyposis (FAP) need total colectomy with ileorectal anastomosis (IRA) or ileal pouch-anal anastomosis (IPAA). The timing of prophylactic colectomy and the type of surgical treatment are controversial in children. The clinical features, the assessment of cancer risk, and the alternatives of the surgical treatment of polyps are reviewed in this paper.

Nonneuropathic Neuropathic Bladder-Is it Really Nonneuropathic?

PURPOSE: Hinman syndrome is a rare disease with urodynamic findings and a clinical course resembling neuropathic bladder, without a neuropathic etiology. Diffusion tensor imaging is a special technique of magnetic resonance imaging that has recently been used to evaluate the peripheral nerves but has been demonstrated to be applicable for evaluation of the lumbosacral plexus. We examined the lumbosacral plexus using diffusion tensor imaging, which has not previously been reported in patients with Hinman syndrome. MATERIALS AND METHODS: The study included 12 patients who fulfilled criteria for Hinman syndrome, with severe bladder dysfunction on urodynamics, renal scarring on scintigraphy and no pathological findings on magnetic resonance imaging. The 12 subjects serving as controls required pelvic or spinal magnetic resonance imaging for reasons other than spinal abnormalities. Evaluation was performed with a 3.0 Tesla magnetic resonance imaging system and 16-channel body coil. Tractography was done to examine the lumbosacral plexus. Fractional anisotropy and mean diffusivity were computed and compared between groups for the right and left plexuses. RESULTS: Mean fractional anisotropy was 0.24 and 0.35 for the right plexus in patients and controls, respectively, and 0.24 and 0.36 for the left plexus. Mean diffusivity was 1.39 for the right and left plexuses in patients, and 1.28 for the right and left plexuses in controls (p <0.001 for all). CONCLUSIONS: Our study focusing on the lumbosacral plexus as a possible origin of neuropathy revealed abnormal findings in patients with Hinman syndrome resembling nerve injury series. This is the first known study to provide data showing that Hinman syndrome may have a neuropathic etiology.

Gestational Outcomes of Pregnancies with Prenatally Detected Gastroschisis and Omphalocele.

Objective: To evaluate and compare the outcomes of pregnancies with prenatally detected gastroschisis and omphalocele. Materials and Methods: We retrospectively evaluated prenatally detected gastroschisis and omphalocele cases. Cases were compared in terms of maternal demographic and clinical characteristics as well as pregnancy and neonatal outcomes. Results: This study consisted of 17 gastroschisis and 30 omphalocele cases. Only one case with gastroschisis was terminated due to additional severe limb deformities. Seventeen out of 30 cases of omphalocele were terminated for various reasons (56.7%). All patients with gastroschisis had surgical repair, while 8 out of 13 omphalocele cases had surgery. One patient with an omphalocele died after surgery due to sepsis. Six cases of gastroschisis also died in the neonatal period due to various reasons (6/16, 37.5%). Conclusion: Additional genetic disorders are more frequent in those with omphalocele cases, and they are more frequently terminated during gestation that the gastroschisis fetuses.

Neuroencorine Tumor Arising within a Tailgut Cyst in an Adolescent Boy.

INTRODUCTION: Neuroendocrine tumors (NET) within tailgut cysts (TC) are usually seen in middle-aged females. A 14 year-old boy who underwent surgical excision of NET within TC is presented to discuss the clinical features, diagnosis and treatment options. CASE REPORT: A 14-year-old boy with rectal bleeding and constipation had a 5 × 4 cm mass detected upon rectal examination. The cystic mass was totally excised. The histopathological evaluation revealed a low-grade NET within mucularis layer of the cyst showing a positive immunhistochemical staining for cytokeratin and synaptophysin. CONCLUSION: Although, the malignant transition of TC is commonly observed in middle age females, males and children can also be affected. This is first report of a pediatric TC with malignant transformation. Total surgical excision of cysts is mandatory for local control of the disease and chemotherapy should be reserved for the patients who have positive surgical margins.