Many etiological factors causing short stature have already been identified in humans. In the last few years, the advent of new techniques for the detection of chromosomal and molecular abnormalities has made it possible to better identify patients with genetic causes of growth failure. Some of these factors directly affect the development and growth of the skeleton, since they damage the epiphyseal growth plate, where linear growth occurs, influencing chondrogenesis. In particular, defects in genes involved in the organization and function of the growth plate are responsible for several well-known conditions with short stature. These genes play a pivotal role in various mechanisms involving the extracellular matrix, intracellular signaling, paracrine signaling, endocrine signaling, and epigenetic regulation. In this review, we will discuss the genes involved in extracellular matrix disorders. The identification of genetic defects in linear growth failure is important for clinicians and researchers in order to improve the care of children affected by growth disorders.

Disorders of sexual development (DSDs) are characterized by a heterogeneous group of congenital conditions associated with atypical development of the sex chromosomes, gonadal or anatomical sex. We report the case of a child with an isolated micropenis, a typical feature of the 46,XY DSD showing low basal testosterone levels and post-stimulation with the hCG test. Molecular analysis using a next-generation sequencing (NGS) panel of 50 genes involved in DSDs was performed, revealing a heterozygous mutation, c.1040G > ANM_000102.4, in the CYP17A1 gene. Sanger sequencing was used to confirm the gene variant detected by NGS; it was also performed to his parents, revealing the presence of the same mutation in the mother, who presented no features of the disease. Then, the serum steroid profile was determined by liquid chromatography coupled to tandem mass spectrometry analysis. Interestingly, this analysis highlighted low levels of testosterone, progesterone, and dehydroepiandrostenedione, as also confirmed by a stimulus test with ACTH. These results suggest that, in some cases, heterozygous mutations in recessive genes involved in adrenal steroidogenesis can also affect the patient’s phenotype.

Seasonal variations in glycaemic patterns in children and young adults affected by type 1 diabetes are currently poorly studied. However, the spread of Flash Glucose Monitoring (FGM) and continuous glucose monitoring (CGM) systems and of dedicated platforms for the synchronization and conservation of CGM reports allows an efficient approach to the comprehension of these phenomena. Moreover, the impact that environmental parameters may have on glycaemic control takes on clinical relevance, implying a need to properly educate patients and their families. In this context, it can be investigated how blood glucose patterns in diabetic patients may have a link to outdoor temperatures. Therefore, in this study, the relationship between outdoor temperatures and glucose levels in diabetic patients, aged between 4 and 21 years old, has been analysed. For a one-year period (Autumn 2022–Summer 2023), seasonal variations in their CGM metrics (i.e., time in range (TIR), Time Above Range (TAR), Time Below Range (TBR), and coefficient of variation (CV)) were analysed with respect to atmospheric temperature. The results highlight a negative correlation between glucose in diabetic patients and temperature patterns (R value computed considering data for the entire year; Ry = −0.49), behaviour which is strongly confirmed by the analysis focused on the July 2023 heatwave (R = −0.67), which shows that during heatwave events, the anticorrelation is accentuated. The diurnal analysis shows how glucose levels fluctuate throughout the day, potentially correlating with atmospheric diurnal temperature changes in addition to the standard trend. Data captured during the July 2023 heatwave (17–21 July 2023) highlight pronounced deviations from the long-term average, signalling the rapid effects of extreme temperatures on glucose regulation. Our findings underscore the need to integrate meteorological parameters into diabetes management and clinical trial designs. These results suggest that structured diabetes self-management education of patients and their families should include adequate warnings about the effects of atmospheric temperature variations on the risk of hypoglycaemia and about the negative effects of excessive therapeutic inertia in the adjustment of insulin doses.

Androgen insensitivity syndrome (AIS) is one of the most common Disorders of Sexual Differentiation (DSDs). AIS is characterized by an X-linked recessive inheritance pattern associated with variants in the androgen receptor (AR) gene that affects the masculinization process in individuals with XY karyotype. Here, we report a neonatal case of a very early diagnosis of complete AIS due to a novel variant in the AR gene. In the present case, after the clinical evaluation, the infant has undergone the following tests: biochemical analyses, including newborn screening workflow, karyotype analysis, and Next-Generation Sequencing (NGS) panel of 50 genes involved in DSDs. The NGS analysis identified a missense variant, c.2108C>A, in the AR gene. According to a cytogenetic analysis, the patient presented a 46, XY karyotype, thus the resulting hemizygote for the AR gene variant. The variant is not currently described in the literature nor in the ClinVar database. However, according to computational models, the variant could have a pathogenetic effect. This clinical case reveals a novel variant of the AR gene with a possible pathogenetic effect associated with AIS and highlights the importance of a multidisciplinary approach for the timely diagnosis and appropriate follow-up of the patient.

The association between type 1 diabetes (T1D) and coeliac disease (CD) is well known. Metabolic control of thirty-seven patients aged between 1 and 18 years, with coexisting T1D and CD were evaluated. The control group includes 37 patients affected only by diabetes. All data relating to the metabolic control of all patients were acquired through examination of medical records and CMG reports available on dedicated online platforms. Glucose variability was expressed as Coefficient of Variation (CV) and Standard Deviation of blood glucose values (SD). The formula used for CV computation is: CV (%) = 100 × SD (daily glycemia)/Mean (daily glycemia). Patients with T1D and CD showed a significant reduction in rapid pre-prandial insulin. The same reduction was present if we consider only patients using CGM. In patients without CGM, there was no difference in the doses of basal, pre-prandial and total insulin. Indicators of metabolic control were overlapping between the two groups in patients who used CGM. On the contrary, diabetic and coeliac patients without CGM had increased levels of glycaemic variability indicators and HbA1c. Finally, the percentage of target glycaemic values and >250 mg/dL glycaemic values were significantly decreased and increased, respectively in T1D and CD patients without CGM. With this study we wanted to demonstrate if CGM could improve metabolic control of patients with coexisting T1D and CD. Our data show a worse metabolic control in patients with T1D and CD who did not use CGM. Instead, patients who use CGM, regardless of the concomitant CD, manage to achieve the same glycaemic targets through an adjustment of titration of pre-prandial insulin doses.

An overview of seasonal variations in glycaemic patterns in children and young adults with type 1 diabetes has been addressed in a previous work, which paved the way for an in-depth study involving not only traditional Multiple Dose Injection (MDI) therapy, but also a comparative analysis with the use of Advanced Hybrid Closed-Loop (AHCL) insulin pumps. The widespread use of Flash Glucose Monitoring (FGM) and Continuous Glucose Monitoring (CGM) systems, as well as dedicated platforms for synchronizing and storing CGM reports, has facilitated an efficient approach to analyzing glycaemic patterns. The effect of environmental parameters on glycemic trends undoubtedly has a clinical relevance, which however can be appropriately managed by knowing the responses in patients treated with different therapeutic approaches. In this sense, it is possible to evaluate how the glycemic trend in diabetic patients, in relation to external temperatures, responds differently to therapies. In this work, the response, in terms of glucose level, in diabetic patients was analyzed, according to the different therapeutic approaches and in relation to variations in external temperature. For the same period of the previous work (one year: Autumn 2022–Summer 2023), seasonal variations in CGM metrics (i.e., Time In Range—TIR, Time Above Range—TAR, Time Below Range—TBR and Coefficient of Variation—CV) were analyzed. The results show a better metabolic control, linked to the effect of the algorithm on the trend of glycaemia. However, the analysis focused on the heatwave of July 2023 highlights the role of extreme temperatures as a stress factor in the insulin pumps performance. A further focus was carried out on the comparison of glycaemic patterns during the school and non-school period for all patients until 21 years old. Results suggest that during the school period, glycaemic patterns, in patients treated with MDI, show a greater onset of hyperglycaemia. From all that has emerged, it appears clear that structured education on diabetes self-management for patients and their families is fundamental and must take into account multiple factors (type of therapy, daily activities, atmospheric temperature) in order to keep their effects under control.