The skeletal abnormalities of mucopolysaccharidosis(MPS) and skeletal dysplasia(SD) may be similar and even indistinguishable. This study aims to elucidate clinical clues and overlapping features that may assist in the different diagnosis. The clinical features of patients who were first referred to endocrinology or rheumatology department for short stature or joint abnormalities were addressed and signs were examined upon different diagnosis. Three patients(I, II and III) were diagnosed with SD with overlapping and also distinguishing skeletal features compared with MPS. An atypical presentation defined in patient IV who was diagnosed with Morquio syndrome. Patients V and VI were diagnosed with MPS with early onset and typical skeletal features accompanied with additional systemic manifestations uncommon in SD. In conclusion,t his study emphasizes the clinical and radiological evaluation and nuances distinctions in clinical presentations that will highlight the challenges and guide to distinguishing different diagnosis of MPS and SD in atypical presentations for achieving the accurate diagnosis.

Bannayan-Riley-Ruvalcaba Syndrome (BRRS) is a rare genetic disorder caused by germline mutations in the phosphatase and tensin homolog (PTEN) gene, leading to overgrowth and classified under PTEN hamartoma tumor syndrome (PHTS). It manifests with systemic features, including cutaneous, neurodevelopmental, and skeletal abnormalities, and is strongly associated with cancer risk. A literature review was conducted using PubMed and Web of Science databases up to April 2025, focusing on BRRS etiology, clinical features, diagnosis, and management. Most BRRS cases involve germline PTEN mutations, though some patients lack them. Clinical manifestations vary, with macrocephaly, lentiginous genital macules, intestinal polyps, and vascular anomalies being most common. Diagnosis is difficult due to the absence of standardized criteria; therefore, phenotypic assessment, molecular testing, imaging, and age-based considerations are essential. Management requires a multidisciplinary approach aimed at symptom control, early detection of malignancy, and family screening. Early recognition of BRRS features, along with prompt referral and intervention, can significantly improve outcomes. The lack of diagnostic guidelines and limited treatment options highlights the need for further research to establish standardized diagnostic and therapeutic strategies.

22nd chromosome deletion syndrome (22q11.2 DS, del22q11.2) (with severe immunological disorders – Di Georg syndrome (SDH) or Di Giorgi syndrome (SDD)) It is one of the most common microdeletion syndromes. The disease is based on a violation of the formation of organs originating from the third gill arch. There is a full form of del22q11.2 syndrome with severe primary immunodeficiency (PID), congenital heart defects (CHD), hypoparathyroidism, facial skeletal abnormalities and high mortality during the first year of life, and partial forms without PID and calcium-phosphorus metabolism disorders. The high variability of clinical manifestations explains the fact that there are many different names of the disease in the literature: Di Giorgi syndrome (SDD), Di Georg syndrome (SDH), CATCH 22, velocardiofacial syndrome, Kyler syndrome, Sprintzen syndrome, facial and conotruncal abnormalities, etc. The term «Di Giorgi syndrome» is applicable to cases of deletion of 22q11.2 chromosome occurring with immune disorders. Despite the availability of genetic testing, many cases of 22q11.2 deletion syndrome remain undiagnosed due to its multsystem nature and varying severity of clinical manifestations, which is associated with a high risk of life-threatening complications. We present data from a 9-year-old patient with a partial form of deletion syndrome 22q11.2, when the reason for contacting an endocrinologist was the early appearance of secondary sexual characteristics against the background of decompensated primary hypothyroidism (Van Wyk-Grombach syndrome) in the absence of violations of phosphorus-calcium metabolism and PID. This clinical case demonstrates not only the variability of the clinical symptoms of the disease, but also the need for coordinated interaction of specialists from various specialties to diagnose polymorphic chromosomal pathology.

In Indonesia, several unregistered traditional Chinese medicines (UTCM) are still used to treat gastritis in pregnancy. On the other hand, the safety of medications during pregnancy remains unresolved. This study aims to investigate the teratogenic effect of UTCM containing Atractylodis lancea radix, Glycyrrhizae glabra radix, Rheum officinale rhizome, and Angelica dahurica radix on fetal morphology. A total of 80 pregnant mice were divided into four groups including the negative control (N), given vehicle, as well as treatment groups D1, D2, and D3 given a dose of 35.2 mg/kg BW, 70.5 mg/kg BW and 105.65 mg/kg BW daily respectively. The drugs were administered between the 6th and 15th days of organogenesis. On the 18th day of pregnancy, a laparotomy was conducted. The teratogenic effects were determined by measuring maternal and fetal body weight, the number of fetuses, and skeletal abnormalities in mouse fetuses, visualised with Alizarin solution. All data were analysed using ANOVA. The results showed that in all treatment groups, there was a substantial difference in maternal body weight, fetal number, and fetal body weight (p<0.05). There were open eyelids and clubfoot abnormalities observed in all groups, while 27 fetuses with haemorrhages were found in D3. All treatment groups had sternal, sacral, caudal, phalanges and metacarpal abnormalities. UTCM administration showed fetal development effects at the early stage of pregnancy in mice. The dose (D3) 105.65 mg/kg BW affected maternal weight gain and fetal skeletal ossification. UTCM administration D1 (35.2 mg/kg BW), D2 0.5 mg/kg BW), and D3 (105.65 mg/kg BW) had no maternal toxicity and fetal teratogenesis.

Hajdu-Cheney Syndrome (HCS) is an exceedingly rare connective tissue disorder primarily manifested by skeletal abnormalities including acro-osteolysis, severe osseous demineralization, distinctive craniofacial/dental abnormalities and short stature. The syndrome is caused by gain-of-function mutations in the NOTCH2 gene, which disrupt bone remodeling and connective tissue integrity. While hearing loss is a known clinical manifestation of HCS, specific imaging findings have not been reported. We present the case of a 36-year-old male with HCS who underwent high-resolution CT of the temporal bones for evaluation of longstanding bilateral conductive hearing loss, which showed relatively symmetric, diffuse osseous demineralization of the temporal bones, with ossicular and otic capsule involvement.ABBREVIATIONS: HCS＝ Hajdu-Cheney Syndrome; CT = Computed Tomography; OI = Osteogenesis Imperfecta.

Short stature is a prevalent clinical manifestation in children. While certain causes of short stature can be readily identifiable through routine biological tests, often physicians struggle to ascertain any underlying pathogenic cause, resulting in the diagnosis of idiopathic short stature (ISS). Aggrecan, encoded by ACAN, plays a crucial role in cartilage function and bone growth. The aim of our study is to establish a genotype-phenotype correlation in 24 patients carrying distinct ACAN variants. We conducted a panel-based analysis, including 82 genes associated with genetic skeletal disorders and/or short stature, in 388 French patients who consulted for short stature and/or or skeletal features. Genotype-phenotype correlation analysis was performed for all included subjects.Of all positive patients, 24(≃20%) were found to carry pathogenic or likely pathogenic ACAN variants distributed across the gene, 20 of which had not been previously reported. We report 23 heterozygous cases and one original case with a homozygous SNV. Two patients harboured the same novel nonsense variant, yet exhibited different phenotypes. Familial studies performed in 21 families demonstrated that ACAN variants were inherited in 20 cases. The cohort demonstrated marked phenotypic heterogeneity, even among affected members within the same family. Radiological skeletal abnormalities were observed in 66% of patients. A comprehensive genomic approach is crucial to identify the true proportion of ISS with a monogenic condition. Our results expand the number of pathogenic ACAN variants with their associated phenotypic spectrum. Aggrecanopathies are heterogeneous and particularly frequent in apparently ISS, even without overt skeletal dysplasia.

Study on the mechanism of skeletal deformity of Lateolabrax maculatus induced by low temperature stress.

BACKGROUND: Anomalies of occlusion in the sagittal plane (distal and mesial occlusion) occupy the first place in the structure of all maxillary-facial anomalies, and the lack of consensus among specialists on the diagnosis and treatment planning of such patients determines the relevance of their study. The use of a stable, extracranial landmark such as the forehead and the glabella soft tissue point opens up the possibility of determining the optimal position of the jaws in the sagittal plane in the cranial space, which would be unique for each patient. To assess the optimal position of the jaws in the sagittal plane relative to the forehead of patients, it is customary to use hard-to-reach manual diagnostic meters and templates. Therefore, until now, the study of maxillary-facial anomalies using unique human landmarks remains inaccessible to specialists. A new diagnostic platform for assessing the position of the jaws in the sagittal plane using a 3D photo of the face can solve this problem. Against the background of obtaining new diagnostic data, there is a need for a comparative assessment of manual and programmatic methods for diagnosing the position of the jaws in the sagittal plane. AIM: To compare manual and new digital methods for determining the optimal position of the jaws in the sagittal plane. METHODS: The study was conducted at the MOSORTO Orthodontics clinic, as well as on the basis of the UNIDENT dental clinic network, from March 1 to October 31, 2025. 50 patients (25 men and 25 women) aged 18-50 years (mean age 32±3.4 years) were examined with skeletal abnormalities of occlusion in the sagittal plane. All the subjects underwent diagnosis and planning of orthodontic treatment according to the unique human guidelines (Six Elements of Orofacial Harmony), first by manual (manual) method, then using a new digital diagnostic platform. Both methods (manual and using software) were compared with each other by 6 parameters. RESULTS: Correlation analysis (Spearman's rank correlation coefficient) showed that a statistically significant positive correlation was found in all the compared parameters (p0.0001). For most measurements, the error ranges from 3 to 8%. CONCLUSION: The new diagnostic platform for assessing the position of the jaws in the sagittal plane based on unique landmarks using 3D facial photos is comparable to a manual technique for diagnosing and planning treatment of anomalies of the maxillary system in the sagittal direction.

A 15-year-old intact female Siberian Husky was referred for hindlimb paresis, anorexia, and cachexia. Cardiac auscultation revealed a grade 5/6 systolic murmur, with maximum intensity over the right hemithorax. Right lateral thoracic radiography revealed an undulating thoracic aorta with a normal vertebral heart scale. The patient had a left-sided scoliosis deformity at the lower thoracic and upper lumbar levels. In addition, sternum deformity revealed pectus excavatum, with no history of trauma in the anamnesis. Echocardiographic examination revealed aortic regurgitation (5.29 m/sn) and dilation of the aortic root and proximal ascending aorta in the parasternal long-axis view. The left ventricle was mildly enlarged, and the left atrial diameter was within reference ranges. This case describes an uncommon combination of skeletal and cardiovascular abnormalities in an elderly dog, raising the suspicion of a connective tissue disorder. However, in the absence of molecular or histopathological confirmation, the diagnosis remains presumptive. The case highlights the need for further genetic investigations and the establishment of specific diagnostic criteria for connective tissue fragility syndromes in veterinary medicine.

Primary renal tubular acidosis is an inherited disorder with heterogeneous clinical presentations, including chronic metabolic acidosis, electrolyte imbalances (e.g., hypokalemia), skeletal abnormalities, and urinary tract symptoms. We report a noteworthy case of a 7-month-old infant who presented with recurrent vomiting and hypokalemia. Laboratory investigations confirmed hypokalemia, metabolic acidosis with hyperchloremia, and inappropriately alkaline urine, leading to a strong suspicion of primary renal tubular acidosis. Genetic analysis by whole-exome sequencing identified a novel homozygous missense mutation (c.1418C &amp;gt; T) in the ATP6V0A4 gene on chromosome 7 in the proband. This specific variant is exceptionally rare and is associated with a severe, atypical phenotype manifesting in early infancy. This case expands the known mutational and phenotypic spectrum of ATP6V0A4 -related renal tubular acidosis. Our findings aim to enhance the understanding of this disease by correlating the clinical course with its genetic etiology, thereby establishing a molecular basis for precise etiological diagnosis, informed genetic counseling, and prenatal diagnosis.

Introduction Myotonic dystrophy (DM), the most common adult-onset muscular dystrophy, affects not only motor function and muscle integrity but also leads to debilitating cardiopulmonary, gastrointestinal, and multisystem complications. Central nervous system (CNS) involvement is increasingly recognized, manifesting as impairments in working memory, executive function, sleep regulation, and mood and behavior. These interrelated, multisystemic features contribute to multifaceted symptoms that significantly reduce quality of life for patients and their families. To identify potential biomarkers of CNS disease activity in DM1, we performed the first exploratory cerebrospinal fluid (CSF) proteomic profiling study. Methods CSF samples from patients with DM1 ( n = 11) and healthy controls ( n = 5) were analyzed using Olink monoclonal antibody panels, quantifying 1,072 proteins. LASSO (Least Absolute Shrinkage and Selection Operator) regression identified proteins discriminating between DM1 and controls. Pathway enrichment analysis was performed using the Reactome database to assess biological significance. Results Six candidate biomarker proteins were differentially expressed between between DM1 patients and controls: CKAP4, SCARF1, NCAM1, CD59, PTH1R, and CA4. LASSO analysis further identified 15 proteins discriminating DM1 and controls, implicating pathways related to neuronal health, neuroinflammation, cognitive impairment, skeletal abnormalities, motor control, neuromuscular junction integrity, and cytoskeletal regulation. Dysregulated pathways included IGF transport, MAPK signaling, NCAM signaling, and broader signal transduction cascades pathways also implicated in other neurodevelopmental, neurodegenerative, and neuromuscular disorders. Discussion This first exploratory CSF proteomic analysis in DM1 identified dysregulated protein networks that may underlie CNS dysfunction in this multisystemic disease. These findings provide novel insights into DM1 pathophysiology and support the potential of CSF proteomic signatures as candidate diagnostic tools, indicators of disease activity, and measures of therapeutic response, pending validation in larger, independent cohorts.

BackgroundNeurofibromatosis type 1 (NF1; 613113) is a hereditary neurocutaneous disorder that causes tumors in the nervous system, significantly impacting the quality of life (QoL). It is characterized by diverse clinical manifestations, including café-au-lait macules (CALMs), axillary or inguinal freckling, Lisch nodules, skeletal abnormalities, and various types of neurofibromas. Plexiform neurofibromas (PN), a common complication of NF1, are often inoperable and prone to recurrence. The study aimed to describe the clinical characteristics and healthcare burden of NF1, including those with PN and those receiving Selumetinib therapy, in Saudi Arabia.MethodsThis retrospective observational study was conducted at the National Guard Health Affairs King Abdulaziz Medical City in Saudi Arabia. Patient medical records were retrospectively reviewed from January 2016 to January 2024. We included all patients diagnosed with NF1 who fulfilled the National Institutes of Health (NIH) diagnostic criteria in 2021 or had a confirmed pathogenic NF1 variant on genetic testing.ResultsA total of 60 patients with NF1 were included; 55.2% of them were females. CALMs were the most common cardinal criteria, affecting 80% of the patients. Among NF1 patients, 12 had PN (20%). Only four patients received Selumetinib therapy. Genetic testing was performed in 39 patients, revealing pathogenic NF1 variants in 29 (74.4%). Pain medications were used by eight patients (13.3%). NF-1-related pain negatively impacted patients’ attention (24%), outdoor activities (24%), and social interactions with friends (20%). Among NF1 patients, 28 (46.7%) required hospitalization, twelve ER visits were conducted by seven (11.7%) NF1 patients, and outpatient services were utilized by nearly all NF1 patients (96.7%), with 1076 outpatient visits. The overall financial burden was high, with NF1 patients incurring $64.5 million, PN patients $13.5 million, and PN patients treated with Selumetinib $3.7 million.ConclusionThis study highlights the clinical and healthcare challenges of NF1 and PN in Saudi Arabia, emphasizing the need for a multidisciplinary approach that combines medical, psychological, and financial support. The limited access to Selumetinib represents a gap. Increasing treatment accessibility and financial support are key to improving the outcomes and QoL.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13053-025-00325-8.

Marinesco–Sjögren syndrome (MSS) is a rare autosomal recessive neuromuscular disorder marked by ataxia, muscle weakness, cataracts, and often intellectual and skeletal abnormalities. It is commonly caused by loss-of-function variants in the SIL1 gene, which impair binding immunoglobulin protein (BiP) function, leading to protein misfolding and activation of the unfolded protein response. In a 2-year-old patient with typical MSS symptoms, we identified a previously unreported c.1024G&gt;A (p.E342K) variant in SIL1 via whole-exome sequencing. The pathogenicity of this Sil1 variant was supported by evidence of structural changes revealed through in silico predictions, circular dichroism, and native gel electrophoresis. Patient-derived fibroblasts exhibited reduced Sil1 protein levels, likely due to misfolding and degradation, which was partially rescued by proteasome inhibition. Proteomics revealed a profile similar to known MSS cases and a distinctive MSS transcriptional signature. Ultrastructural analysis confirmed typical MSS features, such as autophagic vacuoles and lipid droplets. Although the p.E342K phenotype appears milder than the reference pathogenic variant R111X, our findings support the reclassification of this novel variant as pathogenic, in accordance with the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) 2015 guidelines and the refinements proposed by the Clinical Genome Resource Sequence Variant Interpretation (ClinGen SVI) recommendations. Furthermore, the overall evidence also provides important insights into the genotype–phenotype correlation and the underlying pathogenic mechanism of the p.E342K variant.

X-linked hypophosphatemia is characterized by skeletal abnormalities, particularly lower limb angular deformities. Although burosumab has demonstrated short-term clinical improvements, its mid- to long-term effects on skeletal alignment remain underexplored. This study evaluated skeletal outcomes of burosumab therapy over 2 years, focusing on lower limb deformities. We retrospectively analyzed 20 pediatric X-linked hypophosphatemia patients (10 boys and 10 girls) who initiated burosumab at a mean age of 7.5 ± 2.4 years. Rickets severity score, mechanical axis deviation, mechanical lateral distal femoral angle, medial proximal tibial angle, lateral distal tibial angle, and standing height were assessed at baseline, 12 months, and 24 months. Outcomes were analyzed using age-standardized z-scores. Rickets severity improved from the first year, with Rickets Severity Score decreasing from 3.5 ± 1.2 to 0.6 ± 0.5 at 24 months (mean change 2.9; 95% confidence interval 2.4-3.4). Lower limb alignment also improved: |z|-mechanical axis deviation decreased from 2.3 ± 1.6 to 1.0 ± 1.0 (change 1.3; 95% confidence interval 0.9-1.7), showing progressive correction from the first year. |z|-mechanical lateral distal femoral angle improved mainly at 24 months, decreasing from 2.7 ± 2.1 to 1.3 ± 1.2 (change 1.4; 95% confidence interval 0.8-2.0). |z|-medial proximal tibial angle and |z|-lateral distal tibial angle showed smaller overall changes (0.8 and 0.9, respectively), indicating modest tibial correction. Standing-height z-scores remained stable (-1.5 ± 0.8 to -1.3 ± 0.7), with no measurable change in growth over 2 years. Burosumab therapy may improve skeletal deformities in pediatric X-linked hypophosphatemia. Early improvements in rickets severity were followed by gains in alignment, particularly mechanical axis deviation and mechanical lateral distal femoral angle, though standing height remained unaffected. Longer-term follow-up is required to confirm sustained skeletal benefits. Level IV.

IntroductionRubinstein-Taybi syndrome type 2 (RSTS2; OMIM #613684) is a rare autosomal dominant disorder caused by loss-of-function variants in the EP300 gene (OMIM #602700), characterized by intellectual disability, distinctive craniofacial features, and skeletal anomalies.MethodsWhole-exome sequencing (WES) was performed on five pediatric patients presenting with neurodevelopmental delay. Candidate variants were filtered using the TGex platform and validated by Sanger sequencing for familial segregation analysis. The functional impact of variants was assessed using diverse bioinformatic tools, and pathogenicity classifications were assigned according to ACMG/AMP guidelines.ResultsFive novel EP300 variants were identified in this study: c.4774A>G (p.Lys1592Glu), c.4452 + 5G>C, c.3764A>G (p.His1255Arg), c.3591–2A>G, and c.6439C>T (p.Gln2147*). These alterations impair gene function through mechanisms including amino acid substitution, disruption of mRNA splicing, or premature protein truncation. All variants were classified as pathogenic or likely pathogenic per ACMG/AMP criteria. Literature analysis reveals that the predominant clinical manifestations in the Chinese patients encompassed neurodevelopmental impairment, accompanied by motor delay, growth retardation, and microcephaly. Strikingly, archetypal craniofacial dysmorphisms, such as arched eyebrows, long eyelashes, downslanting palpebral fissures, beaked nose, as well as significant skeletal abnormalities were absent, suggesting EP300 variants may present with a broader and more variable phenotypic spectrum than previously recognized.ConclusionThis study reports five novel pathogenic EP300 variants, expanding the variant repertoire of RSTS2 and providing an important basis for clinical diagnosis and genetic counseling.

In fish, sex determination and gonadal development are controlled by various genetic and environmental factors. In this study, experiments were conducted on the estuarine mummichog (Fundulus heteroclitus) to investigate gonadal differentiation following exposure to the synthetic estrogen, 17α-ethinylestradiol (EE2). The period of sensitivity to EE2 was explored by initiating the exposures at different times post fertilization. In Experiment 1, mummichog embryos were collected within 8 h of fertilization and then continually exposed to increasing concentrations of EE2 (up to 229 ng/L) for up to 10 weeks. For controls, complete differentiation of the gonad to a testis or ovary in mummichog occurred by 3 weeks post hatch (wph) and there was an equal distribution of males and females. Exposure to all concentrations of EE2 accelerated female gonadal differentiation as early as 1 wph and contributed to a highly female skewed sex ratio with 80% to 100% of the fish displaying ovaries. Exposure to EE2 also resulted in a concentration-dependent increase in skeletal abnormalities and mortalities whereas larval lengths were not affected. In Experiment 2, 24 h post-hatch larvae were exposed for 5 weeks to three treatments with measured concentrations (ng/L) of 0.4 (Control), 2.5 ng/L, and 18.0 ng/L). The sex ratio was approximately 50/50 in controls and did not change with EE2 treatment. EE2 did not alter the proportion of oocyte stages (chromatin nucleolus, perinucleolar, cortical alveolar) but spermatogenesis was impeded as male fish had greater proportions of spermatogonia, and spermatids were only observed in controls. EE2 treatment did not change the expression of genes in the ovary implicated in gonadal development including cyp19a1a, foxl2, gdf9, bmp15, dmrt1, and amh. In contrast, testis expression of dmrt1 was decreased and cyp19a1a, foxl2, gdf9, and amh were increased following EE2 treatment. Overall, by the time of hatching (about 3 weeks post fertilization), sex differentiation was complete, and the sex determination mechanisms were only sensitive to EE2 during a window of embryonic development before hatch. Early stages of testis differentiation may be more sensitive to exogenous EE2 exposure than ovarian tissue in the mummichog.

USP9X gene variations have been associated with the rare syndrome female-restricted X-linked syndromic intellectual disability (MRXS99F). Loss-of-function mutations in USP9X gene is primarily characterized by development delay, speech and motor disorders, special facial features and multiple congenital malformations. We reported a newborn who presented with special facial features and developmental delay. We performed whole-genome sequencing and identified a rare novel heterozygous USP9X variant, c.4071-4077delCTTTACT (p.Thr1359Trpfs*19). To date, only seven USP9X variants in infants have been reported. Affected individuals typically exhibit a spectrum of congenital anomalies, including craniofacial dysmorphisms (such as hypertelorism, flat nasal bridge, and cleft palate), skeletal abnormalities (such as limb shortening, scoliosis, and rib anomalies), and neurological deficits (including severe intellectual disability, epilepsy, and motor delay). The radio logical tests revealed structural anomalies, such as corpus callosum agenesis and congenital hip dysplasia. This study expands the genotypic and clinical phenotypic spectrum of USP9X-related MRXS99F and reinforces the utility of whole-genome sequencing in early diagnosis and genetic counseling.

Abstract INTRODUCTION Neurofibromatosis type 1 (NF1) is a common autosomal dominant genetic disorder characterized by variable clinical expression and a predisposition to tumor development. Plexiform neurofibromas (PNs), a hallmark and often debilitating feature, contribute significantly to morbidity. This study presents a retrospective, single-center analysis of NF1 patients at King Faisal Specialist Hospital &amp; Research Centre (KFSHRC) in Riyadh, Saudi Arabia, focusing on the distribution of PNs and associated comorbidities. METHODS We retrospectively reviewed the records of all patients diagnosed with NF1 at KFSHRC between 2020 and 2025. Data were extracted from electronic medical records, including demographics, family history, NF1 diagnostic criteria, PN presence and distribution, associated comorbidities, and additional tumor types. RESULTS Fifty-one NF1 patients were identified (28 females, 54.9%; 23 males, 45.1%). The most common clinical features included café-au-lait macules (n = 46, 90.2%) and cutaneous neurofibromas (n = 31, 60.8%), with PNs present in 25 patients (49.0%). Other features included skinfold freckling (33.3%), Lisch nodules (21.6%), skeletal abnormalities (13.7%), and optic pathway gliomas (11.8%). Parental consanguinity was noted in 21.6%, and a family history of NF1 in 60.8%. The mean age at NF1 diagnosis was 4.8 years, with PNs typically emerging by 8.2 years. Among PN patients, 44% had multiple tumors. PN distribution involved the extremities (56%), trunk (48%), head (24%), orbit (24%), neck (20%), face (8%), and other regions (12%). Common comorbidities included headache (13.7%), scoliosis (11.8%), epilepsy (9.8%), visual impairment (9.8%), cognitive delay (3.9%), and malignant peripheral nerve sheath tumors (3.9%). Additional tumors included gliomas (n = 5), schwannomas (n = 3), and rhabdomyosarcoma (n = 1). CONCLUSION This cohort of NF1 patients exhibited a high prevalence of plexiform and cutaneous neurofibromas, along with diverse comorbidities and tumor manifestations. These findings underscore the need for early diagnosis, multidisciplinary management, and sustained surveillance to optimize outcomes in this complex patient population.

Anatomic assessment of palatal temporary skeletal anchorage devices insertion sites among patients with cleidocranial dysplasia vs controls: A retrospective cone-beam computed tomography analysis.

Porcine circovirus 3 (PCV-3) is associated with various pathological conditions, including systemic disease and reproductive disorders; however, its role in skeletal abnormalities has never been elucidated. This study included 36 cases displaying spinal malformations, rib swelling, head edema, gait abnormalities, and/or increased late-term abortions. Investigated animals consisted of 9 aborted fetuses, 9 piglets, 12 weaners, and 6 finishers. Histologically, PCV-3 associated lesions were identified in 23/36 cases (64%), including (peri-)arteritis and rib fractures with prominent callus formation. Central nervous system (CNS) lesions, in addition to vascular changes, comprised meningoencephalitis and gliosis. Thirteen animals (36%) did not display histological lesions. PCV-3 DNA was detected by real-time PCR (qPCR) in 25/36 animals (69%), with high viral loads in the bone and CNS. Three aborted fetuses tested positive for PCV-3 despite lacking macroscopic and histologic lesions. In situ hybridization (ISH) revealed the presence of PCV-3 RNA in multiple organs, including arteries, the heart, CNS, and bone. Signals were detected in periosteal arteries and osteoblasts, within calluses, and in arteries within the surrounding skeletal muscles. This study strengthens the association between PCV-3 and multisystemic inflammatory diseases, expanding its known pathogenicity to include skeletal lesions and spinal deformities. It is the first documentation of PCV-3 genome in histologically altered bone. This finding could suggest a possible etiological role in musculoskeletal abnormalities. In addition, this study is the first to report PCV-3-associated lesions in slaughter-ready finisher pigs. The integration of histological investigations, PCR, and ISH techniques is essential for the diagnosis of PCV-3-associated diseases and related lesions.