Reclassification of two germline DICER1 splicing variants leads to DICER1 syndrome diagnosis.

DICER1 syndrome is an inherited condition associated with an increased risk of developing hamartomatous and neoplastic lesions in diverse organs, mainly at early ages. Germline pathogenic variants in DICER1 cause this condition. Detecting a variant of uncertain significance in DICER1 or finding uncommon phenotypes complicate the diagnosis and can negatively impact patient care. We present two unrelated patients suspected to have DICER1 syndrome. Both females (aged 13 and 15 years) presented with multinodular goiter (thyroid follicular nodular disease) and ovarian tumours. One was diagnosed with an ovarian Sertoli-Leydig cell tumour (SLCT) and the other, with an ovarian juvenile granulosa cell tumour, later reclassified as a retiform variant of SLCT. Genetic screening showed no germline pathogenic variants in DICER1. However, two potentially splicing variants were found, DICER1 c.5365-4A>G and c.5527+3A>G. Also, typical somatic DICER1 RNase IIIb hotspot mutations were detected in the thyroid and ovarian tissues. In silico splicing algorithms predicted altered splicing for both germline variants and skipping of exon 25 was confirmed by RNA assays for both variants. The reclassification of the ovarian tumour, leading to recognition of the association with DICER1 syndrome and the characterization of the germline intronic variants were all applied to recently described DICER1 variant classification rules. This ultimately resulted in confirmation of DICER1 syndrome in the two teenage girls.

The effect of GnRH stimulation on AMH regulation in central precocious puberty and isolated premature thelarche.

OBJECTIVES: There is a complex interaction between the anti-müllerian hormone (AMH) and hypothalamic-pituitary-gonadal axis. However, the effect of gonadotropin-releasing hormone (GnRH) stimulation on AMH levels is not clearly known. In the study, we aimed to evaluate the effect of GnRH stimulation on AMH levels in central precocious puberty (CPP) and isolated premature thelarche (PT) groups. METHODS: Sixty-three girls with breast development before the age of 8 were enrolled in the study. GnRH test was performed on all subjects. Blood samples for follicle-stimulating hormone (FSH), luteinizing hormone (LH), and AMH levels were taken at basal, 40th, and 90th minute of GnRH test. Subjects were grouped as CPP and PT group. RESULTS: After GnRH stimulation, AMH levels increased significantly at the 40th minute and the stimulating effect of GnRH on AMH continued till the 90th minute (p: 0.0001). There was a positive correlation between basal and 90th-minute AMH levels (r: 479, p: 0.0001). The highest FSH, LH, and AMH times were significantly different after the GnRH stimulation (p: 0.001, p: 0.001, and p: 0.007). Although the CPP group had a lower basal AMH level than the PT group's basal AMH level; AMH response to GnRH stimulation was not different (p>0.05). CONCLUSIONS: In our study, which examined the effect of GnRH stimulation on AMH levels in early pubertal development disorders for the first time, GnRH stimulated AMH secretion rapidly, correlated with basal AMH. Basal AMH levels were lower in patients with CPP than in those with PT; however, the effect of GnRH stimulation on AMH levels was similar in both groups.

Local Ocular Surface Alterations in Children with Hashimoto's Thyroiditis.

PURPOSE: To evaluate the ocular surface characteristics based on Schirmer's test, tear break-up time (TBUT), and conjunctival impression cytology (CIC) in children with Hashimoto's thyroiditis (HT). METHODS: This study included 51 children with HT and 53 control subjects. The ocular surface characteristics of participants were assessed via Schirmer's test, TBUT, and CIC. Conjunctival samples were examined cytologically according to the Nelson grading system. RESULTS: Schirmer's and TBUT results were significantly lower in HT group (p < .05). All samples in both the study and control groups were evaluated as grade 0 according to the Nelson classification (p = .841), however, goblet cell density (GCD) was significantly lower in HT group (p = .001). Schirmer test results were significantly associated with the duration of HT (p = .025, r = -0.311). CONCLUSION: Hashimoto's thyroiditis without any ocular complaints may cause ocular surface changes with TBUT and Schirmer's. Although CIC analysis showed similar grading results, GCD was significantly decreased in HT group.

Renal complications of lipodystrophy: A closer look at the natural history of kidney disease.

OBJECTIVES: Lipodystrophy syndromes are a group of heterogeneous disorders characterized by adipose tissue loss. Proteinuria is a remarkable finding in previous reports. STUDY DESIGN: In this multicentre study, prospective follow-up data were collected from 103 subjects with non-HIV-associated lipodystrophy registered in the Turkish Lipodystrophy Study Group database to study renal complications in treatment naïve patients with lipodystrophy. METHODS: Main outcome measures included ascertainment of chronic kidney disease (CKD) by studying the level of proteinuria and the estimated glomerular filtration rate (eGFR). Kidney volume was measured. Percutaneous renal biopsies were performed in 9 patients. RESULTS: Seventeen of 37 patients with generalized and 29 of 66 patients with partial lipodystrophy had CKD characterized by proteinuria, of those 12 progressed to renal failure subsequently. The onset of renal complications was significantly earlier in patients with generalized lipodystrophy. Patients with CKD were older and more insulin resistant and had worse metabolic control. Increased kidney volume was associated with poor metabolic control and suppressed leptin levels. Renal biopsies revealed thickening of glomerular basal membranes, mesangial matrix abnormalities, podocyte injury, focal segmental sclerosis, ischaemic changes and tubular abnormalities at various levels. Lipid vacuoles were visualized in electron microscopy images. CONCLUSIONS: CKD is conspicuously frequent in patients with lipodystrophy which has an early onset. Renal involvement appears multifactorial. While poorly controlled diabetes caused by severe insulin resistance may drive the disease in some cases, inherent underlying genetic defects may also lead to cell autonomous mechanisms contributory to the pathogenesis of kidney disease.

Evaluación de 200 pacientes pediátricos expuestos al riesgo de contraer rabia / Assessment of 200 pediatric patients exposed to rabies risk

Antecedentes/Objetivo: La rabia continúa siendo un grave problema de salud pública, especialmente en los países subdesarrollados o en vías de desarrollo. El objetivo de este estudio fue investigar las características demográficas y los programas de vacunación de los pacientes ingresados con diagnóstico presuntivo de rabia al Centro de Emergencias Pediátricas de nuestro hospital, que funciona como uno de los centros de vacunación antirrábica de nuestra provincia. Métodos: En este estudio, se analizaron retrospectivamente las historias clínicas de 200 pacientes ingresados al Centro de Emergencias Pediátricas con presunta exposición al virus de la rabia. Resultados: Entre los 200 casos, se halló que el riesgo de contraer rabia era mayor en el grupo de 5 a 9 años. El 68,5% de los casos tenían antecedentes de haber sido mordidos por un perro; el 29,5%, de haber sido rasguñados por un gato; y el 2%, de haber tenido contacto con otros animales. En el 76% de los casos se trataba de animales callejeros, solamente el 11% tenían dueño y habían sido vacunados, y estaban bajo supervisión. Se administró solamente la vacuna antirrábica al 42,5% de los pacientes ingresados, la vacuna antirrábica y la vacuna antitetánica al 51,5%, y la vacuna antirrábica, la vacuna antitetánica y concentrado de inmunoglobulinas antirrábicas al 6%. Se detectó que la profilaxis postexposición se había realizado según las recomendaciones en el 83,5% de los casos. Conclusión: La rabia continúa siendo un problema de salud pública grave en los países en vías de desarrollo, como el nuestro. Consideramos que es necesario sensibilizar a la sociedad; las autoridades locales deben esforzarse por luchar contra los animales callejeros y supervisar los servicios; el personal de la salud involucrado debe actualizarse mediante capacitaciones para reducir los casos de rabia.

Background/Purpose: Rabies is still an important health problem particularly in underdeveloped or developing countries. In this study, the aim was to investigate demographic characteristics and vaccination schedules of cases suspected of having rabies and admitted to the Pediatric Emergency Clinic of our hospital, which serves as one of the Rabies Vaccination Centers in our province. Methods: In our study, medical records of 200 patients admitted to the Pediatric Emergency Clinic with suspicion of risk of contact with the rabies virus were retrospectively analyzed. Results: Of those 200 cases, rabies risk was found to be greater in the 5-9 year old group. There was a history of having been bitten by dogs in 68.5% of cases, cat scratch in 29.5%, and contact with other animals in 2%. While 76% of animals were stray animals, only 11% of them had an owner and had been vaccinated, and were under supervision. Rabies vaccination only had been administered to 42.5% of admitted patients, tetanus and rabies vaccination to 51.5%, tetanus; rabies vaccination and human rabies immune globulin were administered to 6%. Post-exposure prophylaxis was found to have been given as recommended to 83.5% of cases. Conclusion: Rabies remains an important public health problem in developing countries Like ours. We consider that public awareness should be raised; local authorities should devote efforts to control stray animals and supervise such services, and updated guidance and training should be provided to the concerned health staff to reduce the risk of rabies.

Assessment of 200 pediatric patients exposed to rabies risk.

BACKGROUND/PURPOSE: Rabies is still an important health problem particularly in underdeveloped or developing countries. In this study, the aim was to investigate demographic characteristics and vaccination schedules of cases suspected of having rabies and admitted to the Pediatric Emergency Clinic of our hospital, which serves as one of the Rabies Vaccination Centers in our province. METHODS: In our study, medical records of 200 patients admitted to the Pediatric Emergency Clinic with suspicion of risk of contact with the rabies virus were retrospectively analyzed. RESULTS: Of those 200 cases, rabies risk was found to be greater in the 5-9 year old group. There was a history of having been bitten by dogs in 68.5% of cases, cat scratch in 29.5%, and contact with other animals in 2%. While 76% of animals were stray animals, only 11% of them had an owner and had been vaccinated, and were under supervision. Rabies vaccination only had been administered to 42.5% of admitted patients, tetanus and rabies vaccination to 51.5%, tetanus; rabies vaccination and human rabies immune globulin were administered to 6%. Post-exposure prophylaxis was found to have been given as recommended to 83.5% of cases. CONCLUSION: Rabies remains an important public health problem in developing countries Like ours. We consider that public awareness should be raised; local authorities should devote efforts to control stray animals and supervise such services, and updated guidance and training should be provided to the concerned health staff to reduce the risk of rabies.

Method of the diagnosis of adenoid hypertrophy for physicians: adenoid-nasopharynx ratio.

OBJECTIVE: We aimed to describe the feasibility of a prediction of adenoid hypertrophy by pediatricians for diagnostic accuracy of nasopharyngeal x-ray in a pediatric unit. METHODS: Forty-six patients with a history of probable adenoid hypertrophy between January 2013 and August 2013 were included in the study. Participants were excluded from the study if they had previous adenoidectomy; anatomic anomaly in the nose, palate, or nasopharynx; and acute infection. Nasal endoscopy was performed and evaluated adenoid size (choanal obstruction ratio) in all patients by an otorhinolaryngologist who was blinded to the information of other data. Lateral nasopharyngeal x-ray graphs of all patients were evaluated by pediatricians with adenoid-nasopharynx (A-N) ratio, who were blinded to the information of other data. The A-N ratio was calculated by Fujioka method. The A-N ratio of each patient was compared with the choanal obstruction ratio that was determined in the nasal endoscopic examination. Spearman correlation test was used for statistical analysis, and P < 0.05 was described as significant. RESULTS: Forty-six patients were included in this study. The study sample consisted of 25 male (54.3%) and 21 female (45.7%) patients. The mean age of the patients was 6.17 years (range, 2-14 y). In the nasal endoscopic examination, the mean (SD) choanal obstruction ratio was 64.6% (19.5%) (range, 12.5%-90%). Mean (SD) A-N ratio was found to be 16.7 (14.4). The A-N ratio correlated with nasal endoscopic examination findings (r = 0.334, P = 0.023) CONCLUSIONS: The A-N ratio was found to be a useful, tolerable, and confident diagnostic method in pediatric patients for adenoid hypertrophy. Pediatricians can confidently use this method for decision after follow-up or operation.