Genetic analyses in a cohort of pediatric patients with congenital hypothyroidism based on congenital hypothyroidism consensus guideline.

INTRODUCTION: Pathogenic variants in the genes involved in the formation of thyroid tissue and thyroid hormone secretion have been reported to cause congenital hypothyroidism (CH) in some cases. This study aimed to evaluate the clinical and genetic findings of CH cases thought to be due to genetic variants. METHODS: The study included cases whose genetic analysis was performed in accordance with the Congenital Hypothyroidism: A 2020-2021 Consensus Guidelines Update Guidelines recommendations criteria and analyzed them using the next-generation sequencing panel. RESULTS: 61 Turkish patients from 45 families were included in the study. The overall frequency of variant detection was 37.7% (Out of 45 families, 17 had a positive mutation). Segregation was carried out for all families with positive variants. Variants in the TPO gene are the most frequently encountered, and this situation was identified in 10 families. Variants followed this in the TSHR gene in 7 families, variants in the DUOX2 gene in 5 families, and two variants in the TG and NKX2-1 genes in 2 families each, which are six novel variants. Furthermore, among the NKX2-1 cases, one had thyroid involvement only, while the other had chorea only. We did not find differences between cases with detected mutations and mutation-negative cases regarding gender, neonatal/perinatal parameters, initial thyroid function values, and thyroid morphology. CONCLUSION: In the current investigation, rare new variations in genes known to be related to CH were discovered, adding to the molecular genetic spectrum. When we compare the overall variant detection frequency, the selection criterion for genetic analysis based on the current guidelines is quite rational, considering the benefits and costs, on the other hand, present in new genes awaiting discovery. Also, TSHR mutations are likely to be common and may account for more than 5% of thyroid dysgenesis cases if we include non-familial thyroid dysgenesis.

Pediatric Oropharyngeal Tularemia Cases: Challenges in Management.

Background: Tularemia is one of the most prevalent zoonoses across the world. Patients in Turkiye mostly contract the oropharyngeal form, acquired through drinking, or contact with microorganism-contaminated water. Methods: Patients with oropharyngeal tularemia aged under 18 years and diagnosed between January 01, 2017, and December 31, 2020, were evaluated retrospectively. Tularemia was diagnosed in patients with compatible histories, symptoms, clinical presentations, and laboratory test results. Results: The mean age of 38 children was 12.1 ± 3.4 years, and the female/male ratio was 0.58 (14/24). The mean duration of symptoms on admission was 33.8 ± 26.2 days. All children had enlarged lymph nodes. Malaise, fever, and loss of appetite were other frequent symptoms. Patients were treated with antibiotics for a mean of 26.2 ± 18.8 days. Gentamycin was the most frequently used antibiotic (either alone or in combination) (n = 29, 76.3%). Twenty-six (68.4%) patients underwent surgical procedures in addition to antibiotherapy. Five (13.2%) required secondary total excision. Patients with higher leukocyte counts at admission received a combination of antibiotherapy plus surgery, rather than antibiotics alone. No relapses, reretreatment requirement, or mortality were observed after 12 months of follow-up. Conclusions: Oropharyngeal tularemia in children can require longer courses of antibiotic treatment with more than one drug and more frequent surgery than previously suggested in the literature, especially if the patients are admitted late to the hospital, symptom duration is prolonged, and appropriate treatment is initiated late. Higher leukocyte counts on admission may be prognostic for longer antibiotic treatment course and suppurative complications that require surgery. Raising awareness among patients and physicians is essential.

Genetic Forms of Calciopenic Rickets.

Rickets is a disease involving calcium and phosphate balance disturbances in the pediatric population. A series of hereditary disorders known as vitamin D-dependent rickets are defined as early-onset rickets resulting from either an insufficient response to active vitamin D or an inability to maintain adequate levels of the active forms of vitamin D. According to the age at onset and the pathophysiology of the disease, various clinical signs including growth failure, limb bowing, and joint enlargement may be present. Vitamin D-dependent rickets type 1A, type 1B, type 2A, type 2B, and type 3 are classified as genetic forms. Further studies are crucial for the development of targeted therapies and future mutation-specific therapies.

A Genetic Approach in the Evaluation of Short Stature.

Short stature is considered a condition in which the height is 2 standard deviations below the mean height of a given age, sex, and population group. Human height is a polygenic and heterogeneous characteristic, and its heritability is reported to be approximately 80%. More than 600 variants associated with human growth were detected in the genome-wide association studies. Rare and common variants concurrently affect human height. The rare variations that play a role in human height determination and have a strong impact on protein functions lead to monogenic short stature phenotypes, which are a highly heterogeneous group. With rapidly developing technologies in the last decade, molecular genetic tests have begun to be used widely in clinical genetics, and thus, the genetic etiology of several rare diseases has been elucidated. Identifying the genetic etiology underlying idiopathic short stature which represents phenotypically heterogeneous group of diseases ranging from isolated short stature to severe and syndromic short stature has promoted the understanding of the genetic regulation of growth plate and longitudinal bone growth. In cases of short stature, definite molecular diagnosis based on genetic evaluation enables the patient and family to receive genetic counseling on the natural course of the disease, prognosis, genetic basis, and recurrence risk. The determination of the genetic etiology in growth disorders is essential for the development of novel targeted therapies and crucial in the development of mutation-specific treatments in the future.

The First Turkish Case of Hypoparathyroidism, Deafness and Renal Dysplasia (HDR) Syndrome.

Hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome is an autosomal dominant genetic disorder characterized by hypoparathyroidism, sensorineural deafness and renal dysplasia. We herein present the first Turkish patient with HDR syndrome, who has a p.R367X mutation. This report indicates that p.R367X is not a mutation specific for the Far Eastern populations and also that urological findings in infants with hypoparathyroidism should be carefully examined because clinical findings relating to the p.R367X mutation may show a variable age of onset.