Thomas Zoller

Spondylocarpotarsal synostosis syndrome (SCT) is a rare autosomal recessive skeletal dysplasia caused by biallelic loss-of-function variants in FLNB, characterized by disproportionate short stature, progressive vertebral fusion, scoliosis, and carpal (typically capitate–hamate) synostosis, classically without rib anomalies. We performed a systematic literature search of PubMed/MEDLINE and Scopus, supplemented by citation searching, following the PRISMA 2020 statement, to identify all reports providing original, molecularly confirmed FLNB-related SCT patient data. Eleven eligible publications, spanning Taiwanese, Argentinian, Pakistani, Italian, German and Indian cohorts, were included in a qualitative synthesis together with a novel case. The novel patient, an adopted child of Indian origin, presented with severe disproportionate short stature, multisegmental vertebral fusion and posterior arch clefts extending from the cervical to the sacral spine, coccygeal dysgenesis, capitate–hamate fusion, and global developmental delay; targeted exome sequencing identified a novel homozygous frameshift FLNB variant. Integration of this case with the reviewed literature confirms disproportionate short stature, contiguous vertebral fusion, and carpal synostosis as near-universal core features, while tarsal fusion, hearing loss, and facial dysmorphism are variably present. The extent and multisegmental pattern of axial involvement in our patient appear more severe than in most previously reported cases, broadening the recognized phenotypic spectrum of FLNB-related SCT and reinforcing the need for structured, multidisciplinary long-term follow-up.

Hajdu–Cheney syndrome (HCS) is a rare genetic skeletal disorder caused by truncating variants of NOTCH2, characterized by progressive bone resorption and marked phenotypic heterogeneity. Despite advances in understanding Notch signaling in skeletal biology, longitudinal clinical data tracking disease evolution from early childhood through adolescence are lacking. Here, we report a rare longitudinal intrafamilial observation of HCS in a mother and her son carrying the same NOTCH2 pathogenic variant, providing novel insights into disease evolution and therapeutic response. Over extended follow-up, the son exhibited early vertebral fragility despite preserved or supranormal bone mineral density (BMD), whereas the mother developed severe osteoporosis, progressive acro-osteolysis, and multiple vertebral fractures. Longitudinal analysis revealed a dissociation between vertebral fragility and densitometric decline, challenging the paradigm that low BMD is the primary driver of skeletal morbidity in HCS. Treatment responses differed between the two patients, with bisphosphonate therapy in the son associated with stabilized BMD without altering vertebral structural progression, and denosumab in the mother associated with increased BMD, but not preventing progression of acro-osteolysis. Additionally, the emergence of extra-skeletal features during adolescence expands the phenotypic spectrum of HCS and suggests previously unrecognized systemic involvement. These data highlight intrinsic limitations of current therapeutic strategies and emphasize the need for targeted interventions addressing sustained Notch2 activation. Our findings contribute to the understanding of the natural history and therapeutic challenges of HCS, providing the framework for future mechanistic and translational research.

Purpose We analyzed patients with chronic endocrinopathies who transited in our clinic in Verona from 2010 to 2023 to assess the effectiveness of the transition process by measuring adherence to follow-up visits, experience and satisfaction with the transition process, the perception of their self-management skills and the assessment of the quality of life of these patients. Methods 70 patients with nine different chronic endocrinopathies were included in this study. Clinical data have been collected through the consultation of medical records. Moreover, subjects have been offered an online, anonymous questionnaire. Adherence to follow-up visits was assessed by detecting the last control visit. A Numerical Rating Scale (NRS) measured satisfaction with the transition process. Evaluation of the perception of one’s self-management skills and quality of life was carried out through the “On Your Own Feet–Self-Efficacy Scale” (OYOF-SES) and SF-36®, respectively. Results We found a drop-out rate from follow up of 28.6%, which is in line with the data in the literature, with significant variability among the individual endocrinological diseases. 82% of the subjects were satisfied with their experience at the Transition Clinic. There was a good capacity for self-management, with high scores obtained at OYOF-SES. The perceived quality of life is also overall good, except for mental health, which was lower than the reference healthy population. Conclusions Despite the improvement in the drop-out rate and the results in terms of self-management and quality of life obtained by our Transition Clinic in Verona, constant analysis and implementation of individualized transition processes are necessary to ensure their optimum effectiveness, paying greater attention to the quality of mental health.

Osteogenesis imperfecta (OI) type XIV is a rare recessive disorder caused by TMEM38B pathogenic variants that disrupt an endoplasmic reticulum protein essential for calcium homeostasis and bone mineralization. This leads to severe bone fragility, early-onset fractures, skeletal deformities, low bone mass, scoliosis, and variable features like blue sclerae or dental abnormalities. We present a case report of a 21-year-old Italian male with a novel homozygous TMEM38B splice variant (c.112 + 1G > T), detailing the clinical presentation, genetic findings, and therapeutic outcomes. The patient exhibited multiple skeletal deformities and showed a moderate response to bisphosphonate therapy (neridronate). In addition, a systematic review of PubMed and Scopus identified 12 relevant studies from an initial set of 82 publications, encompassing data from 56 patients diagnosed with OI type XIV. Unlike classical collagen-related OI, TMEM38B-related OI necessitates genetic screening beyond classical collagen genes (COL1A1 and COL1A2). While bisphosphonates provide some clinical benefit, persistent fractures underscore the need for long-term management and innovative therapies. This case report and systematic review enhance understanding of OI type XIV and underscore the clinical importance of TMEM38B variants in bone fragility disorders.

Background /Objectives: Childhood obesity represents a growing public health concern. It is closely associated with obstructive sleep apnoea (OSA), which impairs nocturnal breathing and significantly affects neurocognitive and cardiovascular health. This review aims to analyse differences in fat distribution, anthropometric parameters, and instrumental assessments of paediatric OSA compared to adult OSA to improve the diagnostic characterisation of obese children. Methods: narrative review. Results: While adenotonsillar hypertrophy (ATH) remains a primary cause of paediatric OSA, the increasing prevalence of obesity has introduced distinct pathophysiological mechanisms, including fat accumulation around the pharynx, reduced respiratory muscle tone, and systemic inflammation. Children exhibit different fat distribution patterns compared to adults, with a greater proportion of subcutaneous fat relative to visceral fat. Nevertheless, cervical and abdominal adiposity are crucial in increasing upper airway collapsibility. Recent evidence highlights the predictive value of anthropometric and body composition indicators such as neck circumference (NC), neck-to-height ratio (NHR), neck-to-waist ratio (NWR), fat-to-muscle ratio (FMR), and the neck-to-abdominal-fat percentage ratio (NAF%). In addition, ultrasound assessment of lateral pharyngeal wall (LPW) thickness and abdominal fat distribution provides clinically relevant information regarding anatomical contributions to OSA severity. Among imaging modalities, dual-energy X-ray absorptiometry (DXA), bioelectrical impedance analysis (BIA), and air displacement plethysmography (ADP) have proven valuable tools for evaluating body fat distribution. Conclusions: Despite advances in the topic, a validated predictive model that integrates these parameters is still lacking in clinical practice. Polysomnography (PSG) remains the gold standard for diagnosis; however, its limited accessibility underscores the need for complementary tools to prioritise the identification of children at high risk. A multimodal approach integrating clinical, anthropometric, and imaging data could support the early identification and personalised management of paediatric OSA in obesity.

Osteogenesis Imperfecta (OI) is a heterogeneous group of inherited skeletal dysplasias characterized by bone fragility. The study of bone metabolism, in these disease, is problematic in terms of clinical and genetic variability. The aims of our study were to evaluate the importance of Vitamin D levels in OI bone metabolism, reviewing studies performed on this topic and providing advice reflecting our experience using vitamin D supplementation. A comprehensive review on all English-language articles was conducted in order to analyze the influence of vitamin D in OI bone metabolism in pediatric patients. Reviewing the studies, contradictory data were found on the relationship between 25OH vitamin D levels and bone parameters in OI, and in several studies the baseline levels of 25OH D were below the threshold value of 75 nmol/L. In conclusion, according to the literature and to our experience, we highlight the importance of adequate vitamin D supplementation in children with OI.

(1) Objective: To evaluate: (i) the associations of age and disease severity with anthropometric indices and weight status, (ii) the difference in the frequency of sports activity among different levels of disease severity in paediatric patients with congenital heart disease (CHD). (2) Methods: Clinical data of Caucasian children (aged 2–18 years) diagnosed with CHD (2005–2018) were retrospectively collected from the electronic register of outpatient visits. Of the 475 children with CHD, 368 children and their 1690 complete anthropometric measurements were eligible for inclusion in our analysis. (3) Results: Significant increase with age was observed for weight z-score [beta (95%CI): 0.03 (0.02, 0.05) for one-unit of age] and BMI z-score [0.06 (0.03, 0.08)] but not for height z-score. The probability of being underweight and overweight/obese increased and decreased with disease severity, respectively. The obesity probability of patients with mild CHD (0.06 [95%CI: 0.03, 0.08]) was not statistically distinguishable from that of patients with moderate CHD (0.03 [95%CI: 0.02, 0.05]), whereas it was lower in patients with severe CHD (0.004 [95%CI: 0.0, 0.009]). No obese patients with a univentricular heart defect were observed. Days spent in sport activities were equal to 1.9 [95%CI: 1.6, 2.2] days/week, 1.9 [1.5, 2.2], 1.4 [1.1, 1.7] and 0.7 [0.1, 1.3] in patients with mild, moderate, severe and univentricular CHD, respectively. (4) Conclusions: The risk of being overweight and obese should not be underestimated in paediatric patients diagnosed with CHD, especially in children with mild or moderate heart defects. It could be prevented or reduced by promoting a healthy lifestyle.

Objective: To understand the anthropometric changes in paediatric patients with CHD, to evaluate their status and to assess their sport activity frequency.Methods: Of 535 children on follow up, we selected 368 Caucasian children (aged 2-18 years) with CHD, had at least one visit with measured weight and height, with no comorbidities that could influence growth. A total of 1690 complete anthropometric measurements were analyzed. Anthropometric z-scores were computed using formulae based on the LMS method according to Cacciari growth standards.Underweight, overweight and obesity were defined using BMI percentile cut-offs. Sport activity was collected through a phone interview.The CHD severity was classified as mild, moderate, severe, univentricular or unclassified.Results: Significant increase with age was observed for weight z-score [beta (95%CI): 0.03 (0.02,0.05) for one-unit of age] and BMI z-score [0.06 (0.03,0.08)] but not for height z-score. The percentage of underweight increased with disease severity, and the percentages of overweight and obese patients consequently decreased. The percentage of obesity in patients with mild CHD (5.9% [95%CI: 3.4,8.4]) was not significantly different from that in patients with moderate CHD (3.3% [1.5,5.0]), whereas it was lower in patients with severe CHD (0.4% [0.0,0.9]). No obese patients with univentricular heart defect was observed. Days spent in sport activities was equal to 1.9 [95%CI: 1.6,2.2] days/week, 1.9 [1.5,2.2], 1.4 [1.1,1.7] and 0.7 [0.1,1.3] in patients with mild, moderate, severe and univentricular CHD, respectively.Conclusions: Children with mild and moderate CHD present a risk of becoming overweight or obese that could not be underestimated and on the other hand could be prevented or reduced promoting an healthy lifestyle.