The Relationship between Psychopathology, Self-esteem, Body Perception and Serum Sex Steroids in Pubertal Gynecomastia.

OBJECTIVE: The current study aimed to investigate the psychopathology behind gynecomastia and potential associated problems regarding self-esteem and body perception, and the relationships of these variables with sex steroid levels in adolescents with pubertal gynecomastia. METHODS: The study included 50 normal weight male adolescents aged between 11 and 18 years with gynecomastia but without any chronic organic pathology, and 50 healthy pubertal male adolescents matched for age. The adolescents underwent psychopathology assessment by Development and Well-Being Assessment interviews; self-esteem was assessed using the Rosenberg Self-Esteem Scale; body perception was evaluated using the Body Image Perception Scale, and the relationship between these variables and sex steroid levels were explored. RESULTS: The results of the study revealed that the gynecomastia group had significantly greater internalization disorder (X2 = 12.96, p < 0.001), and impairments in self-esteem (z = -1.975, p = 0.024) and body perception (z = -2.286, p = 0.022), and these variables were correlated with the gynecomastia stage. In the study group, cortisol levels were significantly higher (z = -2.330, p = 0.02) in adolescents with internalization disorder compared to those without, and cortisol levels increased in parallel with increased gynecomastia duration (r = 0.386, p = 0.006). CONCLUSION: In our study, we found that gynecomastia, depending on its stage, may lead to internalization disorder and impair self-esteem and body perception. It was found that there was no direct relationship between these parameters and sex steroids in pubertal gynecomastia, except for high cortisol levels in adolescents with internalization disorder.

The Spectrum of Low-Density Lipoprotein Receptor Mutations in a Large Turkish Cohort of Patients with Familial Hypercholesterolemia.

Background: Monogenic hypercholesterolemia with Mendelian inheritance is a heterogeneous group of diseases that are characterized by elevated plasma low-density lipoprotein cholesterol (LDL-C) levels, and the most common form of this disorder is autosomal-dominant familial hypercholesterolemia (FH). Methods: A total of 104 index cases with the clinical diagnosis of FH were included in this study. Low-density lipoprotein receptor (LDLR) was sequenced using the Sanger sequencing method. Results: Pathogenic/likely pathogenic variants were detected in LDLR in 55 of the 104 cases (mutation detection rate = 52.8%). Thirty different variants were detected in LDLR, three of which were novel. The total cholesterol and LDL-C values of the patients in the group of premature termination codon (PTC) mutation carriers were significantly higher than those of the patients in the group of non-PTC mutation carriers. A total of 87 patients (17 pediatric and 70 adult cases) were diagnosed with cascade genetic screening. Statin treatment was recommended to all 87 patients and was accepted and initiated in 70 of these patients. Conclusions: This study is the largest patient cohort that evaluated FH cases in the Turkish population. Herein, we revealed the LDLR mutation spectrum for a Turkish population and compared the cases in the context of genotype-phenotype correlation. Genetic screening of individuals with suspected FH not only helps to establish their diagnosis, but also facilitates early diagnosis and treatment initiation in other family members through cascade screening.

WNT Signaling Perturbations Underlie the Genetic Heterogeneity of Robinow Syndrome.

Locus heterogeneity characterizes a variety of skeletal dysplasias often due to interacting or overlapping signaling pathways. Robinow syndrome is a skeletal disorder historically refractory to molecular diagnosis, potentially stemming from substantial genetic heterogeneity. All current known pathogenic variants reside in genes within the noncanonical Wnt signaling pathway including ROR2, WNT5A, and more recently, DVL1 and DVL3. However, ∼70% of autosomal-dominant Robinow syndrome cases remain molecularly unsolved. To investigate this missing heritability, we recruited 21 families with at least one family member clinically diagnosed with Robinow or Robinow-like phenotypes and performed genetic and genomic studies. In total, four families with variants in FZD2 were identified as well as three individuals from two families with biallelic variants in NXN that co-segregate with the phenotype. Importantly, both FZD2 and NXN are relevant protein partners in the WNT5A interactome, supporting their role in skeletal development. In addition to confirming that clustered -1 frameshifting variants in DVL1 and DVL3 are the main contributors to dominant Robinow syndrome, we also found likely pathogenic variants in candidate genes GPC4 and RAC3, both linked to the Wnt signaling pathway. These data support an initial hypothesis that Robinow syndrome results from perturbation of the Wnt/PCP pathway, suggest specific relevant domains of the proteins involved, and reveal key contributors in this signaling cascade during human embryonic development. Contrary to the view that non-allelic genetic heterogeneity hampers gene discovery, this study demonstrates the utility of rare disease genomic studies to parse gene function in human developmental pathways.

Endothelial dysfunction biomarker, endothelial cell-specific molecule-1, and pediatric metabolic syndrome.

BACKGROUND: The aim of this study was to compare serum endothelial cell-specific molecule-1 (endocan) in pediatric patients with metabolic syndrome (MetS) and in healthy children, and to determine whether it can be used as an indicator of endothelium damage-induced complications in pediatric MetS patients. METHODS: The study included 30 patients, aged 6-16 years, who were diagnosed with MetS. Another 30 children with no diseases were recruited as healthy controls. Endocan concentration was measured using enzyme-linked immunosorbent assay. RESULTS: Endocan was increased almost threefold in the MetS group compared with the healthy group. Systolic arterial tension and diastolic arterial tension, serum triglyceride, total cholesterol, and low-density lipoprotein cholesterol were higher, and high-density lipoprotein cholesterol was lower, in the MetS children than in the healthy group. Fasting blood glucose (FBG), hemoglobin A1c (HBA1C), and homeostasis model assessment insulin resistance (HOMA-IR) were also significantly increased in the children with MetS compared with the healthy group. CONCLUSIONS: Serum endocan level in pediatric MetS patients could be an important indicator of cardiovascular risk in adulthood.

Plasma Kisspeptin Levels in Newborn Infants with Breast Enlargement.

OBJECTIVE: Kisspeptin levels have been reported in children with premature thelarche, precocious puberty and adolescent gynecomastia, but there are no reports on kisspeptin levels in the neonatal period. This study aimed to investigate plasma kisspeptin hormone levels in newborns with and without breast enlargement. METHODS: Plasma kisspeptin levels and other related biochemical variables were investigated in this prospective study conducted on 40 (20 girls and 20 boys) newborn infants with breast enlargement and on 40 healthy control infants (20 girls and 20 boys). Two-milliliter venous blood samples were taken in hemogram tubes with K2EDTA. Kisspeptin assays were performed using the enzyme-immunoassay method. RESULTS: Mean plasma kisspeptin levels were 0.6 ± 0.2 ng/mL in the study group and 0.5 ± 0.2 ng/mL in the control group. Plasma kisspeptin concentrations were significantly higher in the study group (p=0.039) and also showed a correlation with serum prolactin levels (p=0.006). Significant correlations were also determined between plasma kisspeptin and luteinizing hormone concentrations (p=0.05, r=0.312). CONCLUSION: The findings of this study suggest that plasma kisspeptin and serum prolactin levels may be involved in the physiopathology of breast enlargement in newborns.

Holoprosencephaly: ZIC2 mutation in a case with panhypopituitarism.

BACKGROUND: Holoprosencephaly (HPE), the most common malformation of the brain, results from failed or incomplete separation of the embryonic forebrain (prosencephalon). HPE occurs in approximately 1 in 250 embryos and in about 1 in 10,000 births. It is etiologically heterogeneous, and may be caused by cytogenetic anomalies and teratogenic influences; it occurs as part of a syndrome, or due to heterozygous mutations in 1 of over 10 HPE-associated genes. ZIC2 mutations are the second-most common cause of non-syndromic non-chromosomal HPE (after sonic hedgehog) and occur de novo in 74% of the affected probands. OBJECTIVE: The objective of the study was to describe the first case of ZIC2-related HPE with both anterior and posterior pituitary insufficiencies. CASE PRESENTATION: We report about a 2-year-8-month-old boy who was born as a second child in a non-consanguineous healthy Turkish family. He has the characteristic ZIC2 phenotype: bitemporal narrowing, upslanting palpebral fissures, large ears, short nose with anteverted nares and broad and deep philtrum. Magnetic resonance imaging revealed alobar HPE. During laboratory investigation, his blood sodium level was 158 mmol/L and the specific gravity of his urine was 1.002. Serum osmolarity was 336 mOsm/L and urine osmolality was 135 mOsm/kg. His FT4 was 0.8 ng/dL and TSH was 0.79 mLU/mL. Response to vasopressin confirmed the diagnosis of central diabetes insipidus and TRH-stimulating test supported the central hypothyroidism. A frameshift mutation (NM_007129.2:c1091_1092 del, p.Gln364Leufs*2) in the ZIC2 gene was detected. CONCLUSION: Pituitary insufficiency other than isolated diabetes insipidus is a rare finding of HPE, and occurs most frequently in patients with GLI2 mutations (the phenotype of which typically does not include frank neuroanatomic anomalies such as HPE); ours is the only described patient with a ZIC2 mutation and both anterior and posterior pituitary dysfunction.

Combined occurrence of Alström syndrome and bronchiectasis.

Alström syndrome (Online Mendelian Inheritance in Man ALMS #203800) is a rare hereditary disorder caused by mutations in the gene ALMS1. This rare disorder's characteristics are cone-rod dystrophy resulting in blindness in childhood, insulin-resistant type 2 diabetes mellitus, truncal obesity, progressive sensorineural hearing loss, dilated cardiomyopathy, craniofacial features, hypothyroidism, elevation in liver transaminases, renal insufficiency, gonadal dysfunction, and menstrual irregularities. A 13.5-year-old girl was admitted to the hospital for complaints of excessive water consumption and urination over the previous 2 years. The patient's parents were third-degree relatives. At physical examination, hyperpigmentation was present over the areola and acanthosis nigricans under the arms and on the neck. Audiologic examination revealed bilateral sensorineural hearing loss, and bilateral cataract was determined at ocular examination. The patient was monitored by the chest diseases department due to bronchiectasis. HbA1c was 13.1%. In mutation screening study, 2 novel mutations c.5586T>G; p.Tyr1862* and c.2905insT; p.L968fs*4 were detected in the ALMS1 gene. Saccharin test was positive. We emphasize that Alström syndrome may be complicated by bronchiectasis.

Effects of thiamine and thiamine pyrophosphate on epileptic episode model established with caffeine in rats.

This study examines the effect of thiamine (TH) and thiamine pyrophosphate (TPP) on epileptic episode model induced in rats with caffeine. Animals were divided into groups and given TH or TPP at doses of 10, 30 or 50mg/kg intraperitoneally. Subsequently, all animal groups were injected intraperitoneally with caffeine at a dose of 300mg/kg. Time of onset of epileptic episode was recorded, and the latent period was calculated in seconds. At the end of the experiment, tGSH and MDA levels and SOD and MPO enzyme activities in extracted brain tissues were measured. Latent period duration in rats in the control group was 134±3.2s, compared to 144±13.9, 147±14.5 and 169±15.1s, respectively, in the TH10, TH30 and TH50 groups and 184±8.54, 197±9.1, 225±8.37s, respectively, in the TPP10, TPP30 and TPP50 groups. Latent period duration was 236±6.7 in the diazepam group. Oxidant products were significantly lower in the TPP10, TPP30, TPP50 and diazepam groups compared to the control group (P<0.05), while SOD activity and tGSH levels were significantly higher (P<0.05). There was no significant difference between the TH10, TH30, TH50 groups and the control group in terms of oxidant and antioxidant levels (P>0.05). In conclusions, TPP, especially at a dose of 50mg/kg, significantly prolonged the latent period from administration of caffeine to time of episode and prevented oxidative damage.

Serum vitamin D levels in children with recurrent otitis media.

The aims of this study were to evaluate serum vitamin D levels in cases of recurrent otitis media and investigate the effect of vitamin D therapy on the risk of re-occurrence of the disease. This prospective study was performed by comparing serum vitamin D levels in children with recurrent otitis media and healthy children. Eighty-four children between 1 and 5 years of age and diagnosed with recurrent otitis media were enrolled as the study group. One hundred-and-eight healthy children with similar demographic characteristics were enrolled as the control group. Patients were divided into groups according to their serum 25(OH) vitamin D levels. In patients with low initial serum vitamin D levels, vitamin D therapy was administered in addition to conventional treatment for otitis media. Mean serum 25(OH) vitamin D level in the study group was 11.4 ± 9.8 ng/mL Serum 25(OH) vitamin D levels were below 20 ng/mL in 69 % (n = 58) of cases in this group. In the control group, mean serum 25(OH) vitamin D level was 29.2 ± 13.9 ng/mL and was below 20 ng/mL in 30 % (n = 32) of cases. Comparison of serum 25(OH) vitamin D levels and PTH in the study and control groups revealed a statistically significant difference (p < 0.05). Treatment was initiated in cases diagnosed with vitamin D deficiency, and patients were followed up in due course. The only episodes detected over the course of 1-year follow-up were one attack in five patients and two attacks in two. We believe that co-administration of supplementary vitamin D together with conventional treatments is appropriate in the management of upper respiratory infections such as otitis media.

Cystinosis presenting with findings of Bartter syndrome.

A five-year-old boy was referred to our pediatric clinic for evaluation of failure to thrive, headache, intermittent high fever, restlessness, polyuria, and polydipsia. His weight and height measurements were under the 3rd percentile. Clinical findings consisted of frontal bossing, carious teeth, O-bain deformity of the lower extremities, and moderate dehydration. The presence of metabolic alkalosis, hypokalemia, hypochloremia, and high renin and aldosterone levels were suggestive of Bartter syndrome and a treatment regimen for Bartter syndrome was started. At follow-up, the polyuria and hyponatremia were found to persist. A reassessment of the patient revealed findings consistent with proximal renal tubular acidosis such as metabolic acidosis with a high urinary pH, proteinuria, aminoaciduria with phosphaturia and hypercalciuria. Based on the presence of parental consanguinity as well as polyuria, proteinuria, low tubular reabsorption of phosphorus, generalized aminoaciduria, light yellow skin and hair color, the probable diagnosis of cystinosis was established and was confirmed by slit-lamp examination of the cornea showing cystine crystal deposition. Our case is a good example demonstrating that development of metabolic alkalosis does not exclude cystinosis and that all findings of the patient should be thoroughly evaluated.