Happle-Tinschert syndrome in an infant: clinical, radiologic and genetic correlation.

Background:Muscle fatty infiltration (MFI), the pathological replacement of muscle by adipose tissue in chronic diseases, lacks comprehensive genetic characterization despite known cellular contributors. Elucidating its genetic architecture and clinical correlations could reveal therapeutic targets for this debilitating condition.Materials and methods:We performed a genome-wide association study (GWAS) on 33 300 participants’ genomic/MRI data, identifying MFI-associated loci. Fine-mapping (GCTA-COJO/FUMA), Mendelian randomization (tissue-specific genes, plasma proteins, metabolites) and genetic correlation (LDSC) analyses were conducted. KLF5’s functional role was validated through inhibition experiments in fibro-adipogenic progenitors (FAPs) and murine immobilization-induced MFI models.Results:GWAS revealed 91 significant SNPs across 26 loci, with risk genes enriched in olfactory transduction and JAK-STAT pathways. Multi-omics integration identified KLF5 as a key transcriptional regulator, CHRDL2/HLA-E as circulating risk protein, and phosphatidylcholines/triglycerides as causal metabolites, and genetic correlations between MFI and metabolic/musculoskeletal disorders. Experimentally, KLF5 suppression reduced adipo-fibrogenic FAP differentiation and improved muscle histology in mice.Conclusion:Our study delineates MFI’s polygenic basis, establishes clinical-metabolic relationships, and mechanistically validates KLF5 as a target. These findings provide a framework for treating MFI through metabolic modulation or KLF5 inhibition, with broader implications for muscle-degenerative comorbidities.

Over 10% of the population in Europe and in the United States use sleep medication to manage sleep problems. Our objective was to elucidate genetic risk factors and clinical correlates that contribute to sleep medication purchase and estimate the comorbid impact of sleep problems. We performed epidemiological analysis for psychiatric diagnoses, and genetic association studies of sleep medication purchase in 797 714 individuals from FinnGen Release 7 (N = 311 892) and from the UK Biobank (N = 485 822). Post-association analyses included genetic correlation, co-localization, Mendelian randomization (MR), and polygenic risk estimation. In a GWAS we identified 27 genetic loci significantly associated with sleep medication, located in genes associated with sleep; AUTS2, CACNA1C, MEIS1, KIRREL3, PAX8, GABRA2, psychiatric traits; CACNA1C, HIST1H2BD, NUDT12. TOPAZ1 and TSNARE1. Co-localization and expression analysis emphasized effects on the KPNA2, GABRA2, and CACNA1C expression in the brain. Sleep medications use was epidemiologically related to psychiatric traits in FinnGen (OR [95% (CI)] = 3.86 [3.78 to 3.94], p < 2 × 10-16), and the association was accentuated by genetic correlation and MR; depression (rg = 0.55 (0.027), p = 2.86 × 10-89, p MR = 4.5 × 10-5), schizophrenia (rg = 0.25 (0.026), p = 2.52 × 10-21, p MR = 2 × 10-4), and anxiety (rg = 0.44 (0.047), p = 2.88 × 10-27, p MR = 8.6 × 10-12). These results demonstrate the genetics behind sleep problems and the association between sleep problems and psychiatric traits. Our results highlight the scientific basis for sleep management in treating the impact of psychiatric diseases.

Recent research has raised the question of whether age- and IQ-discrepancy forms of reading disability (RD) are distinguishable in terms of either their underlying linguistic deficit or their response to treatment, thus threatening the external validity of the traditional distinction between specific reading retardation and reading backwardness. The present study pursued the external validity of this distinction in three domains: (a) genetic etiology, (b) sex ratio and clinical correlates, and (c) neuropsychological profiles. Each of these domains was explored in the RD (n = 640) and control (n = 436) twins participating in the Colorado Reading Project (514 males, 562 females, with an overall mean age of 12.42 years). Little evidence for external validity was found in terms of the clinical correlates of attention deficit-hyperactivity disorder (ADHD), immune disorders, or handedness. Most importantly, there was no evidence of differential genetic etiology of the two phenotypes in this sample, in that deficits in both phenotypes were similarly heritable (h2g = .40 and .46 for age and IQ phenotypes, respectively) and the genetic correlation between them was high (rG = .88 to .96). However, the genetic and neuropsychological profile analyses did suggest that age- and IQ-discrepancy definitions of RD may relate differentially to component reading processes, such as phonological awareness and orthographic coding.

The aim of this study was to illustrate the capacity of magnetic resonance imaging (MRI) in the accurate delineation of brainstem ischemic strokes allowing precise clinical and radiological correlations. In such a project the computed (CT) tomographic scan is not as sensitive as MRI because of the lack of spatial resolution, the presence of bone artifacts in the posterior fossa, and poor visualisation of infarcted tissue [1]. Brainstem ischemic strokes are frequent, usually small, and have well-known clinical symptoms and signs, so we chose this condition in order to evaluate the quality of clinical and radiological correlations possible with MRI.

Dyggve-Melchior-Clausen syndrome (DMC) is a rare autosomal recessive skeletal dysplasia caused by mutations in the DYM gene, characterized by disproportionate short stature, intellectual disability, and specific radiographic anomalies (EI Ghouzzi et al., 2003, Lapierre et al., 2001). It is often misdiagnosed due to clinical similarities with Morquio syndrome and other skeletal dysplasias. This report presents a four-year-old female from a consanguineous union, evaluated for global developmental delay and growth retardation. Clinical findings included coarse facies, thoracic scoliosis, and short extremities. Radiographs revealed characteristic features such as platyspondyly and irregular iliac crests. Genetic analysis identified a homozygous pathogenic variant in the DYM gene, confirming the diagnosis. Differential diagnosis with mucopolysaccharidoses and Smith-McCort dysplasia was discussed. The importance of early diagnosis through clinical, radiological, and genetic correlation is emphasized to provide anticipatory care and genetic counseling. Although no curative treatment exists, a multidisciplinary approach can improve quality of life and functional outcomes. This case reinforces the diagnostic value of molecular genetics in rare dysplasias.

Fragile X-associated tremor/ataxia syndrome masquerading as normal pressure hydrocephalus - A report with clinical radiological and genetic correlation

Abnormalities in ataxin-2 associated with spinocerebellar ataxia type 2 (SCA2) may lead to widespread disruptions in the proteome. This study was performed to identify dysregulated proteome in SCA2 and to explore its clinical-radiological correlations. Cerebrospinal fluid (CSF) samples from 21 genetically confirmed SCA2 were subjected to shotgun proteome analysis using mass spectrometry (MS) and tandem mass tag (TMT)-based multiplexing. Proteins with at least 1.5-fold change in abundance were identified. Their relative abundance was measured using parallel reaction monitoring (PRM) and correlated against disease-related factors. Eleven proteins were significantly upregulated in SCA2. They belonged to the family of cell adhesion molecules and granins. Their fold changes showed significant clinical, genetic, and radiological correlations. Significant dysregulation of CSF proteome is seen in SCA2. The dysregulated protein may have potential use in clinical evaluation of patients with SCA2.

IntroductionThe critical shoulder angle is defined as the angle formed between the plane of the glenoid and the line connecting the most lateral border of the acromion process, as seen on the true anteroposterior radiograph of the shoulder. The purpose of this study was to determine the association between the critical shoulder angle and shoulder pathologies like rotator cuff tears and glenohumeral osteoarthritis. It was also to assess the reproducibility and accuracy of critical shoulder angle values, which were measured with radiographs. ObjectiveThe aim of the study was to find out the association between the critical shoulder angle and shoulder injuries in a rural population cohort. The secondary aims were to assess clinical and radiological correlations between the critical shoulder angle and the symptomology of shoulder pain.Materials and methodsOur study analysis was a prospective design conducted at R L Jalappa Hospital & Research Centre, Karnataka, South India. After meeting the inclusion and exclusion criteria, 100 patients were recruited for the study. Forty-five patients had glenohumeral osteoarthritis and 55 patients had a diagnosis of rotator cuff tears. The majority of the patients were male (70%) in both the glenohumeral osteoarthritis and rotator cuff tear groups. The mean critical shoulder angles in the glenohumeral osteoarthritis and rotator cuff tear groups were 30.31 and 33.62, respectively.ConclusionsOur data aid in demonstrating that glenohumeral osteoarthritis is associated with a significantly narrower critical shoulder angle and wider critical shoulder angles in rotator cuff disease. Further studies, however, should determine whether this association has a cause-and-effect relationship.

Background and Aims: Fetal growth restriction (FGR) is a significant cause of perinatal morbidity and stillbirth. This study aimed to analyze the prevalence, clinical and radiological correlates, and outcomes of FGR in a secondary care hospital. It also aimed to examine risk factors for low birth weight neonates among mothers with FGR and compare them with those born with normal birth weights. Methods: This study was done at a secondary care hospital in Chittoor, Andhra Pradesh. It is a retrospective cohort study. We retrieved medical records of women diagnosed with FGR who were followed up until delivery. We analyzed risk factors for low birth weight among neonates (and compared them to those with normal birth weights) in the same cohort. Results: One hundred mothers with FGR were among the 1006 mothers who were followed up and delivered at the hospital during the study period. Diabetes mellitus was the most prevalent medical condition observed in 62% of mothers. Other prevalent conditions included anemia (13%), hypothyroidism (12%), and hypertension (11%). A statistically significant correlation was found between the anticipated fetal weight determined by ultrasound and the actual birth weight (interclass correlation coefficient 0.682; P &lt; 0.000). Conclusion: This study adds to the limited data on FGR from secondary hospitals in India. It records the prevalence of FGR in a secondary care hospital at 9.94%. It documents birthweights &lt;2.5 kg among 78% of the neonates and records a significant correlation between such low birth weights and high maternal age and lower gestational age at birth.

Except for the skeleton, the rest of the human body is made of “soft” tissues. However, in a more restrictive way, the term of soft tissue is synonymous to soft connective tissue, most of which is mesenchymal origin. In addition to the skeletal system and the somatic compartments of the body, soft connective tissue also exists in all the visceral organs of the body. Therefore, soft-tissue tumors can also occur in all visceral organs. For practical purpose, the term of soft-tissue tumors is restricted to tumors primarily originating in the soft tissues of the somatic compartments. Because bone is also part of the connective tissue originating from mesenchyme, some tumors of bone and the soft tissues share a similar histology and biology. Thus, differentiating a bone from a soft-tissue origin in these tumors is difficult if not impossible on histologic ground alone because the same tumor can arise independently in either soft tissue or bone and subsequently involve the other. The distinction of primary site in these cases can only be resolved by clinical and radiologic correlation. Nevertheless, many tumors of mesenchymal origin are more prone to arise either in soft tissue or bone and histologic evaluation can help to determine the primary site and extent of the disease with appropriate clinical correlation. The knowledge of soft-tissue tumors can surely benefit the pathologists who frequently deal with bone tumors or tumor-like condition in bone. This chapter is primarily written with this purpose in mind to complement the rest of the contents of the book and not to replace any other major monographs of soft-tissue tumor pathology as bench references for surgical pathologists.

Currently, attention has been given to complications related to breast implants, especially due to the presence of anaplastic large cell lymphoma (ALCL) related to silicone implants. Many manuscripts attempt to associate silicone presence with clinical complaints reported by patients, while others try to demonstrate the mechanisms of silicone bleeding by permeability loss of breast implant surfaces. There also are reports of foreign body type reactions from implant fibrous capsule to silicone corpuscles. However, there seems to be no study that correlates the clinical, radiological, and histological correlations of these lesions. The objective of this review is to correlate radiological findings of silicone-induced granuloma of breast implant capsule (SIGBIC) from breast MRI (BMRI) scans and complementary findings of ultrasound (US) and positron emission tomography (PET) scan, and its histology originated from surgical breast implant capsulectomy. To make this correlation possible, we divided SIGBIC into three radiological findings: (1) intracapsular SIGBIC, (2) SIGBIC with extracapsular extension, and (3) mixed SIGBIC associated with seroma. Our experience demonstrates histological-radiological correlation in SIGBIC diagnosis. Knowledge of these findings may demonstrate its real importance in terms of public health and patient management. We believe that SIGBIC is currently underdiagnosed by lack of training, guidance, and management in our clinical practice.

A cholesteroloma or cholesterol granuloma of the breast is an uncommon lesion representing an inflammatory/reactive process with unclear etiology. In this study, we reviewed our 10-year experience with cholesteroloma of the breast with clinical, radiologic, and histopathological correlation. Seventy-nine cases were selected. The mean patient age was 57.7 (range 25-90) years old. Patients had hypercholesterolemia with mean blood cholesterol level of 201mg/dL (P<0.001). The mean body mass index (BMI) was 26.7kg/m2 (P=0.1976). The indications for the breast biopsies were mass lesion on radiology (85.5%, n=65) and microcalcifications (10.5%, n=8). Of the 65 cases of the mass lesions, 52 presented as solid masses and 13 were cystic. On the diagnostic mammogram or ultrasound, 81.9% were BI-RADS 4% and 6.9% were BI-RADS 5. Macrocysts were the most common pathological finding associated with cholesteroloma suggesting the etiology of cholesteroloma may be the result of repair process from obstruction and rupture of the macrocysts. Six cases (9.2%) of cholesterolomas had persistent masses during follow-up. The recognition of this lesion and radio-pathological correlation can help us better understand this entity and distinguish it from its mimickers.

Introduction. X-linked mental retardation 102 type caused by novel mutations in the DDX3X gene is one of the most common monogenic variants of intellectual deficiency in women.Purpose of the study. Description of the clinical and genetic characteristics of Russian female patients with type 102 mental retardation due to newly identified mutations.Materials and methods. The diagnosis of mental retardation of type 102 was established on the basis of the features of clinical manifestations and the detection of the mutations in the DDX3X gene as a result of exome sequencing and subsequent confirmation of the identified variants of Sanger sequencing.Results. A description is given of the clinical and genetic characteristics of two female patients with type 102 X-linked mental retardation due newly to identified mutations p.1703C&gt; G and c.113A&gt; G (NM_001193416) in the DDX3X gene in the heterozygous state. New features of the phenotype are described. The mechanism of the appearance of clinical and genetic correlations is suggested, which can be used as a prognostic marker of the development of the disease.Conclusion. Clinical and genetic characteristics of two patients with mutations in the DDX3X gene that violate the amino acid sequence of different protein regions with different severity of clinical manifestations are described. The results obtained may testify in favor of the existence of a dependence of the severity of the phenotype on the localization and nature of mutations in the gene and determine the relevance of further research aimed at searching for clinical and genetic correlations.

Congenital hepatic hemangiomas: Clinical, histologic, and genetic correlation

SF3B1 mutations in primary myelofibrosis: clinical, histopathology and genetic correlates among 155 patients