RESUMEN
The cardinal phenotypic hallmarks of Marfan syndrome (MFS) include cardiac, ocular, and skeletal abnormalities. Since the clinical phenotype of MFS is highly heterogeneous, with certain symptoms appearing as children age, the diagnostic process and establishing a genotype-phenotype association in childhood MFS can be challenging. The lack of sufficient childhood studies also makes it difficult to interpret the subject. This study aims to evaluate the relationship between clinical symptoms used as diagnostic criteria and FBN1 variations in children with MFS. This study investigated the relationships between genotypes and phenotypes in 131 children suspected of having Marfan syndrome (MFS). Diagnosis of MFS was made according to the revised Ghent nosology. FBN1 variants were categorized based on exon regions, type of variant, and pathogenicity classes. These FBN1 variants were then correlated with the clinical manifestations including cardiovascular, ocular, facial, and skeletal abnormalities. Out of the children, 43 were diagnosed with MFS. FBN1 variant was identified in 32 (74.4%) of the MFS children. MFS diagnosis could not be made in five (15.6%) FBN1 variant-positive children. The most common cardinal finding is cardiac anomalies n = 38 (88.3%). The most common FBN1 pathogenic variant was c.1786 T > C/p.Cys596Arg n = 4 (12.5%). The distribution of pathogenic variants was as follows: 29 (90.6%) missense, 2 (6.3%) frameshift, and 1 (3.1%) nonsense. The numbers of AD and EL of the variant-positive children were 16 (50%) and 14 (43.7%), respectively. Ocular abnormalities were more common in children with FBN1-positive MFS (p = 0.009). There was no difference in the number of cardiac abnormalities between FBN1-positive and FBN1-negative MFS patients (p = 0.139). Conclusion: This study examines the relationship between FBN1 variants and clinical features used as diagnostic criteria in MFS children. The findings emphasize the importance of long-term monitoring of heterogeneous clinical phenotypes and bioinformatic reanalysis in determining the genotype-phenotype relationship in children, as MFS symptoms can vary with age. What is Known: ⢠Marfan syndrome has highly variable phenotypic heterogeneity. ⢠The genotype-phenotype relationship in childhood Marfan syndrome is not clear enough due to the variation in the time of onset of the findings. What is New: ⢠This article provides regional data for the field of research on genotype-phenotype relationships in childhood Marfan syndrome. ⢠Long-term follow-up of clinical findings and bioinformatics reanalysis is an important requirement for a well-established genotype-phenotype relationship in childhood Marfan syndrome.
Asunto(s)
Fibrilina-1 , Genotipo , Síndrome de Marfan , Fenotipo , Humanos , Síndrome de Marfan/genética , Síndrome de Marfan/diagnóstico , Niño , Femenino , Masculino , Fibrilina-1/genética , Preescolar , Adolescente , Turquía/epidemiología , Lactante , Estudios de Asociación Genética , Mutación , AdipoquinasRESUMEN
Background The olfactory bulb (OB) and eyeball size change depending on age and puberty. There is a well-established trade-off between sensory structures of the brain such as the eye and the olfactory bulb that depend on environmental circumstances in the evolutionary history of animals. The aim of this study was to developmentally investigate the potential reciprocal changes between OB and eyeball volumes (EV) in girls with precocious puberty (PP). Methods A total of 148 girls aged between 5 and 8 years (63 PP, 85 healthy) were included in the study. Exclusion criteria: Cases of anosmia/hyposmia, neurodegenerative disorder, refractive errors and trauma. The pituitary height (PH), EV and OB volumes were measured on segmentation of a magnetic resonance image (MRI) slice using manual countering. The corrected measurements by body surface were used in all statistical analyses. Results In girls with PP, the means of the OB volume and PH were larger (71.11 ± 20.64 mL) and higher (4.62 ± 1.18 mm), respectively, while the mean of EVs was smaller (11.24 ± 2.62 cm3) (p = 0.000). Cut-off values were 62.27 mL, 10.7 cm3 and 4.71 mm for OB volume, EV and PH, respectively. While negative correlations were found between OB volume-EV and EV-PH (r63 = -0.224, p = 0.001 and r63 = -0.116, p = 0.001, respectively), OB volume was positively correlated with PH (r63 = 0.578, p = 0.001). Conclusions The present study demonstrates that girls with PP have significantly larger OB volume, but smaller EV, and there is negative correlation between the two structures. These results indicate that there is trade-off between anatomical dimensions of OB and eyeball in favor of OB in PP girls.
Asunto(s)
Ojo/anatomía & histología , Bulbo Olfatorio/anatomía & histología , Pubertad Precoz/fisiopatología , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Masculino , Tamaño de los Órganos , Pronóstico , Estudios Retrospectivos , Maduración SexualRESUMEN
Objective: To determine the demographic and biochemical features of childhood and juvenile thyrotoxicosis and treatment outcome. Methods: We reviewed the records of children from 22 centers in Turkey who were diagnosed with thyrotoxicosis between 2007 to 2017. Results: A total of 503 children had been diagnosed with thyrotoxicosis at the centers during the study period. Of these, 375 (74.6%) had been diagnosed with Graves' disease (GD), 75 (14.9%) with hashitoxicosis and 53 (10.5%) with other less common causes of thyrotoxicosis. The most common presenting features in children with GD or hashitoxicosis were tachycardia and/or palpitations, weight loss and excessive sweating. The cumulative remission rate was 17.6% in 370 patients with GD who had received anti-thyroid drugs (ATDs) for initial treatment. The median (range) treatment period was 22.8 (0.3-127) months. No variables predictive of achieving remission were identified. Twenty-seven received second-line treatment because of poor disease control and/or adverse events associated with ATDs. Total thyroidectomy was performed in 17 patients with no recurrence of thyrotoxicosis and all became hypothyroid. Ten patients received radioiodine and six became hypothyroid, one remained hyperthyroid and restarted ATDs and one patient achieved remission. Two patients were lost to follow up. Conclusion: This study has demonstrated that using ATDs is the generally accepted first-line approach and there seems to be low remission rate with ATDs in pediatric GD patients in Turkey.