McCune–Albright syndrome (MAS) is a rare sporadic condition defined by the classic triad of fibrous dysplasia of bone, café au lait skin macules, and hyperfunctioning endocrinopathies. The molecular basis of MAS has been ascribed to the post-zygotic somatic gain-of-function mutations in the GNAS gene, which encodes the alpha subunit of G proteins, leading to constitutive activation of several G Protein-Coupled Receptors (GPCRs). The co-occurrence of two of the above-mentioned cardinal clinical manifestations sets the diagnosis at the clinical level. In this case report, we describe a 27-month-old girl who presented with gonadotropin-independent precocious puberty secondary to an estrogen-secreting ovarian cyst, a café au lait skin macule and growth hormone, and prolactin excess, and we provide an updated review of the scientific literature on the clinical features, diagnostic work-up, and therapeutic management of MAS.

Objectives: Rapid-onset obesity with hypoventilation, hypothalamic dysfunction, and autonomic dysregulation (ROHHAD) is a rare, potentially fatal, pediatric syndrome. Case presentations: We describe three cases of ROHHAD-syndrome in Greece. The main and earliest symptom was the excessive and rapid weight gain at 5, 2, and 3 years of age. Years after the onset of obesity, the patients developed hypothalamic dysfunction with various endocrinological abnormalities (at 9, 8, and 6.8 years, respectively), autonomic dysregulation and finally, alveolar hypoventilation (at 14.6, 8, and 7.8 years, respectively), leading to the diagnosis of ROHHAD-syndrome. Conclusions: The rarity of the syndrome, the variable symptoms’ presentation, and the lack of specific diagnostic tests could explain why no previous cases have been reported from our country. The rapid onset of obesity was underestimated, and the patients were misdiagnosed with other more common obesity syndromes. Therefore, we propose a questionnaire to help physicians identify patients with ROHHAD-syndrome.

Combined pituitary hormone deficiency (CPHD) is characterized by deficiency of growth hormone and at least one other pituitary hormone. Pathogenic variants in more than 30 genes expressed during the development of the head, hypothalamus, and/or pituitary have been identified so far to cause genetic forms of CPHD. However, the etiology of around 85% of the cases remains unknown. The aim of this study was to unveil the genetic etiology of CPHD due to congenital hypopituitarism employing whole exome sequencing (WES) in two newborn patients, initially tested and found to be negative for PROP1, LHX3, LHX4 and HESX1 pathogenic variants by Sanger sequencing and for copy number variations by MLPA. In this study, the application of WES in these CPHD newborns revealed the presence of three different heterozygous gene variants in each patient. Specifically in patient 1, the variants BMP4; p.Ala42Pro, GNRH1; p.Arg73Ter and SRA1; p.Gln32Glu, and in patient 2, the SOX9; p.Val95Ile, HS6ST1; p.Arg306Gln, and IL17RD; p.Pro566Ser were identified as candidate gene variants. These findings further support the hypothesis that CPHD constitutes an oligogenic rather than a monogenic disease and that there is a genetic overlap between CPHD and congenital hypogonadotropic hypogonadism.

The aim of the current study was to investigate the tear proteome in children and adolescents with type 1 diabetes (T1D) compared to healthy controls, and to identify differences in the tear proteome of children with T1D depending on different characteristics of the disease. Fifty-six children with T1D at least one year after diagnosis, aged 6–17 years old, and fifty-six healthy age- and sex-matched controls were enrolled in this cross-sectional study. The proteomic analysis was based on liquid chromatography tandem mass spectrometry (LC-MS/MS) enabling the identification and quantification of the protein content via Data-Independent Acquisition by Neural Networks (DIA-NN). Data are available via ProteomeXchange with the identifier PXD052994. In total, 3302 proteins were identified from tear samples. Two hundred thirty-nine tear proteins were differentially expressed in children with T1D compared to healthy controls. Most of them were involved in the immune response, tissue homeostasis and inflammation. The presence of diabetic ketoacidosis at diagnosis and the level of glycemic control of children with T1D influenced the tear proteome. Tear proteomics analysis revealed a different proteome pattern in children with T1D compared to healthy controls offering insights on deregulated biological processes underlying the pathogenesis of T1D. Differences within the T1D group could unravel biomarkers for early detection of long-term complications of T1D.

21-hydroxylase deficiency (21-OHD) represents the most common form of congenital adrenal hyperplasia (CAH) due to CYP21A2 gene pathogenic variants. Τhe aim of this study was the identification of CYP21A2 variants in 500 subjects of Greek origin with a suspicion of 21-OHD and, by using the existing hormonal assessment and genotypes of the 500 subjects tested, to identify a biomarker that could differentiate between the heterozygotes and the cases with no pathogenic variants identified. Five hundred subjects with clinical suspicion of 21-OHD underwent CYP21A2 gene sequencing and Multiplex Ligation Dependent Probe Amplification (MLPA). Genetic diagnosis was achieved in 27.4% of the subjects tested, most of which presented with the non-classic form (NC) of 21-OHD. Heterozygotes accounted for 42.6% of cases, whereas no pathogenic variants were identified in 27% of cases. De novo aberrations, duplications, and five novel variants were also identified. Statistical analysis revealed that the difference between the basal and 60′ post-ACTH stimulation 17-hydroxyprogesterone concentrations (Δ17-OHP^60-0) could be a potential biomarker (p < 0.05) distinguishing the heterozygotes from the cases with no pathogenic variants identified, although no clear cut-off value could be set. Further analysis revealed overlapping clinical manifestations among all the subjects tested. The presented phenotypic traits of the subjects tested and the inability to identify a discriminative biochemical marker highlight the importance of comprehensive CYP21A2 genotyping to ascertain the correct genetic diagnosis and proper genetic counselling.

The COVID-19 pandemic and the consequent restrictive measures may be related to increased stress and anxiety and to changes in daily behaviors. Children with type 1 diabetes (T1D) are a vulnerable group due to their difficulties in achieving glycemic control and to their medical and psychological comorbidities. The purpose of the current study was to the investigate the changes on emotional and behavioral parameters in children with T1D due to the Coronavirus crisis. A total of 152 children and adolescents, aged 5–18, were studied: 114 (62 boys) with T1D and 38 (19 boys) healthy volunteers (HV) (controls). The study was performed at the Diabetes Center, Aghia Sofia Children’s Hospital, during the first national lockdown in Greece. The CRISIS questionnaire was completed by parents/caregivers. The data were collected in May 2020 and referred to two time-points: three months prior (before the pandemic), and the past two weeks. During the lockdown, it was observed significant aggravation in the “Emotion/Worries (EW)” symptoms in both groups (logEW-before vs. logEW-during the crisis, T1D: 2.66 ± 0.23 vs. 3.00 ± 0.21, p < 0.001 and HV: 2.62 ± 0.16 vs. 2.83 ± 0.18, p < 0.001). Deterioration of “ΕW” was recorded for 93.0% of those with T1D and 92.1% of the HV. “EW” during the lockdown were affected by: previous psychological condition, COVID-related concerns, and “Life Changes due to the COVID-19 crisis in the past two weeks (LC)”. Deterioration was observed in the “daily behaviors” and “use of digital media” for all of the children. The crisis and the associated restrictions negatively affected both the lifestyle parameters and the behavioral and emotional variables of the children with T1D.