A 1-Day-Old Girl With Infantile Hemangioma and Sternal Cleft.

CASE PRESENTATION: A newborn girl presented to the hospital on the first day of life because of respiratory failure. She was born at home at 37 weeks' gestation with minimal prenatal care and was found to be small for gestational age. The patient was found to have partial sternal agenesis and sternal cleft, cutis aplasia, left facial hemangioma, micrognathia, wide-spaced nipples, and low-set ears. The mother's and baby's urine toxicology screening were positive for amphetamines. Chest radiographs on admission showed bilateral hazy opacities. CT scan of the chest showed an absent sternum with midline chest wall concavity. The patient was monitored preoperatively in the cardiac ICU for risks of arrythmia, respiratory failure, altered cardiac output, and acute cardiopulmonary decompensation.

Sternal cleft and pectus excavatum: an overlooked congenital association?

BACKGROUND: Sternal cleft (SC), a rare thoracic malformation, is associated with pectus excavatum (PE) in 2.6-5% of cases. It remains unclear if these conditions are congenitally linked or if SC repair triggers PE. To investigate the potential higher frequency of PE in SC cases, we conducted a retrospective study of our SC patients. METHODS: We assessed PE incidence, progression, and management in SC patients treated at our institute from 2006 to 2022. When available, we collected pre-SC repair CT scan data, calculating the Haller Index (HI) and Correction Index (CI) and compared them to a selected control group. RESULTS: Among 8 SC patients, 7 had concomitant PE (87.5%), varying in severity. PE management ranged from observation to thoracoplasty, depending on its degree. We observed a significant pre-operative CI difference between SC and control group patients (p < 0.00001). In the last two SC repair cases, we attempted concurrent PE prevention or treatment. CONCLUSION: Our findings suggest an underestimated association between PE and SC in the existing literature. SC patients may exhibit a predisposition to PE from birth, which may become more apparent with growth after SC repair. Consequently, PE prevention or treatment should be considered during SC repair procedures.

Lineamientos técnicos para la habilitación y rehabilitación de personas con alteraciones musculoesqueléticas / Technical guidelines for the rehabilitation and rehabilitation of people with musculoskeletal disorders

El presente documento desarrolla las diferentes intervenciones en salud desde la promoción de la salud para las alteraciones musculoesqueléticas, prevención de las alteraciones hasta la atención que deberá ser diferenciada, según categorías funcionales en cualquiera de los niveles de atención, incluyendo las instituciones especializadas en habilitación y rehabilitación. Además, se desarrollan las consideraciones para la atención en habilitación y rehabilitación, que los profesionales de salud del SNIS deberán ejecutar, incluyendo los cuidados paliativos necesarios, las ayudas técnicas y tecnologías de asistencia

This document develops the different health interventions from health promotion for musculoskeletal disorders, prevention of disorders to care that must be differentiated, according to functional categories at any of the levels of care, including institutions specialized in habilitation and rehabilitation. In addition, considerations are developed for habilitation and rehabilitation care, which SNIS health professionals must execute, including the necessary palliative care, technical aids and assistive technologies

De novo variants in FRYL are associated with developmental delay, intellectual disability, and dysmorphic features.

FRY-like transcription coactivator (FRYL) belongs to a Furry protein family that is evolutionarily conserved from yeast to humans. The functions of FRYL in mammals are largely unknown, and variants in FRYL have not previously been associated with a Mendelian disease. Here, we report fourteen individuals with heterozygous variants in FRYL who present with developmental delay, intellectual disability, dysmorphic features, and other congenital anomalies in multiple systems. The variants are confirmed de novo in all individuals except one. Human genetic data suggest that FRYL is intolerant to loss of function (LoF). We find that the fly FRYL ortholog, furry (fry), is expressed in multiple tissues, including the central nervous system where it is present in neurons but not in glia. Homozygous fry LoF mutation is lethal at various developmental stages, and loss of fry in mutant clones causes defects in wings and compound eyes. We next modeled four out of the five missense variants found in affected individuals using fry knockin alleles. One variant behaves as a severe LoF variant, whereas two others behave as partial LoF variants. One variant does not cause any observable defect in flies, and the corresponding human variant is not confirmed to be de novo, suggesting that this is a variant of uncertain significance. In summary, our findings support that fry is required for proper development in flies and that the LoF variants in FRYL cause a dominant disorder with developmental and neurological symptoms due to haploinsufficiency.

De novo missense variants in exon 9 of SEPHS1 cause a neurodevelopmental condition with developmental delay, poor growth, hypotonia, and dysmorphic features.

Selenophosphate synthetase (SEPHS) plays an essential role in selenium metabolism. Two mammalian SEPHS paralogues, SEPHS1 and SEPHS2, share high sequence identity and structural homology with SEPHS. Here, we report nine individuals from eight families with developmental delay, growth and feeding problems, hypotonia, and dysmorphic features, all with heterozygous missense variants in SEPHS1. Eight of these individuals had a recurrent variant at amino acid position 371 of SEPHS1 (p.Arg371Trp, p.Arg371Gln, and p.Arg371Gly); seven of these variants were known to be de novo. Structural modeling and biochemical assays were used to understand the effect of these variants on SEPHS1 function. We found that a variant at residue Trp352 results in local structural changes of the C-terminal region of SEPHS1 that decrease the overall thermal stability of the enzyme. In contrast, variants of a solvent-exposed residue Arg371 do not impact enzyme stability and folding but could modulate direct protein-protein interactions of SEPSH1 with cellular factors in promoting cell proliferation and development. In neuronal SH-SY5Y cells, we assessed the impact of SEPHS1 variants on cell proliferation and ROS production and investigated the mRNA expression levels of genes encoding stress-related selenoproteins. Our findings provided evidence that the identified SEPHS1 variants enhance cell proliferation by modulating ROS homeostasis. Our study supports the hypothesis that SEPHS1 plays a critical role during human development and provides a basis for further investigation into the molecular mechanisms employed by SEPHS1. Furthermore, our data suggest that variants in SEPHS1 are associated with a neurodevelopmental disorder.

Skeletal abnormalities in mice with Dnmt3a missense mutations.

Overgrowth and intellectual disability disorders in humans are typified by length/height and/or head circumference ≥ 2 standard deviations above the mean as well as intellectual disability and behavioral comorbidities, including autism and anxiety. Tatton-Brown-Rahman Syndrome is one type of overgrowth and intellectual disability disorder caused by heterozygous missense mutations in the DNA methyltransferase 3A (DNMT3A) gene. Numerous DNMT3A mutations have been identified in Tatton-Brown-Rahman Syndrome patients and may be associated with varying phenotype severities of clinical presentation. Two such mutations are the R882H and P904L mutations which result in severe and mild phenotypes, respectively. Mice with paralogous mutations (Dnmt3aP900L/+ and Dnmt3aR878H/+) exhibit overgrowth in their long bones (e.g., femur, humerus), but the mechanisms responsible for their skeletal overgrowth remain unknown. The goal of this study is to characterize skeletal phenotypes in mouse models of Tatton-Brown-Rahman Syndrome and identify potential cellular mechanisms involved in the skeletal overgrowth phenotype. We report that mature mice with the Dnmt3aP900L/+ or Dnmt3aR878H/+ mutation exhibit tibial overgrowth, cortical bone thinning, and weakened bone mechanical properties. Dnmt3aR878H/+ mutants also contain larger bone marrow adipocytes while Dnmt3aP900L/+ mutants show no adipocyte phenotype compared to control animals. To understand the potential cellular mechanisms regulating these phenotypes, growth plate chondrocytes, osteoblasts, and osteoclasts were assessed in juvenile mutant mice using quantitative static histomorphometry and dynamic histomorphometry. Tibial growth plates appeared thicker in mutant juvenile mice, but no changes were observed in osteoblast activity or osteoclast number in the femoral mid-diaphysis. These studies reveal new skeletal phenotypes associated with Tatton-Brown-Rahman Syndrome in mice and provide a rationale to extend clinical assessments of patients with this condition to include bone density and quality testing. These findings may be also informative for skeletal characterization of other mouse models presenting with overgrowth and intellectual disability phenotypes.

Identification of potential molecular mechanism related to craniofacial dysmorphism caused by FOXI3 deficiency.

BACKGROUND: Hemifacial macrosomia (HFM, OMIM 164210) is a complex and highly heterogeneous disease. FORKHEAD BOX I3 (FOXI3) is a susceptibility gene for HFM, and mice with loss of function of Foxi3 did exhibit a phenotype similar to craniofacial dysmorphism. However, the specific pathogenesis of HFM caused by FOXI3 deficiency remains unclear till now. METHOD: In this study, we first constructed a Foxi3 deficiency (Foxi3-/- ) mouse model to verify the craniofacial phenotype of Foxi3-/- mice, and then used RNAseq data for gene differential expression analysis to screen candidate pathogenic genes, and conducted gene expression verification analysis using quantitative real-time PCR. RESULTS: By observing the phenotype of Foxi3-/- mice, we found that craniofacial dysmorphism was present. The results of comprehensive bioinformatics analysis suggested that the craniofacial dysmorphism caused by Foxi3 deficiency may be involved in the PI3K-Akt signaling pathway. Quantitative real-time PCR results showed that the expression of PI3K-Akt signaling pathway-related gene Akt2 was significantly increased in Foxi3-/- mice. CONCLUSION: The craniofacial dysmorphism caused by the deficiency of Foxi3 may be related to the expression of Akt2 and PI3K-Akt signaling pathway. This study laid a foundation for understanding the function of FOXI3 and the pathogenesis and treatment of related craniofacial dysmorphism caused by FOXI3 dysfunction.

Craniofacial bone anomalies related to cholesterol synthesis defects.

DHCR7 and SC5D are enzymes crucial for cholesterol biosynthesis, and mutations in their genes are associated with developmental disorders, which are characterized by craniofacial deformities. We have recently reported that a loss of either Dhcr7 or Sc5d results in a failure in osteoblast differentiation. However, it remains unclear to what extent a loss of function in either DHCR7 or SC5D affects craniofacial skeletal formation. Here, using micro computed tomography (µCT), we found that the bone phenotype differs in Dhcr7-/- and Sc5d-/- mice in a location-specific fashion. For instance, in Sc5d-/- mice, although craniofacial bones were overall affected, some bone segments, such as the anterior part of the premaxilla, the anterior-posterior length of the frontal bone, and the main body of the mandible, did not present significant differences compared to WT controls. By contrast, in Dhcr7-/- mice, while craniofacial bones were not much affected, the frontal bone was larger in width and volume, and the maxilla and palatine bone were hypoplastic, compared to WT controls. Interestingly the mandible in Dhcr7-/- mice was mainly affected at the condylar region, not the body. Thus, these results help us understand which bones and how greatly they are affected by cholesterol metabolism aberrations in Dhcr7-/- and Sc5d-/- mice.

Congenital hemivertebrae combined with situs inversus totalis: A rare case report.

RATIONALE: Situs inversus totalis is a rare malposition of organs that typically involves lesions in the respiratory, circulatory, or urinary systems. Cases of congenital hemivertebrae combined with situs inversus totalis are extremely rare and have limited reports. PATIENT CONCERNS: We report a 2.5 years old girl with 2 congenital hemipyramids and complete visceral inversion who ultimately underwent hemilaminectomy. DIAGNOSIS: Congenital hemivertebrae combined with situs inversus totalis. INTERVENTION: The patient underwent hemilaminectomy. OUTCOMES: The spinal deformity was corrected. LESSONS: For patient with spinal deformities combined with situs inversus totalis, surgery can be an effective treatment method. But we also need to be vigilant about the dysfunction of various systems.

Novel variants in TNRC6B cause global developmental delay with speech and behavioral abnormalities, short stature, low body weight, café-au-lait spots, and metabolic abnormality.

BACKGROUND: TNRC6B deficiency syndrome, also known as global developmental delay with speech and behavioral abnormalities (MIM 619243), is a rare autosomal dominant genetic disease mainly characterized by facial dysmorphism, developmental delay/intellectual disability (DD/ID), speech and language delay, fine and motor delay, attention deficit and hyperactivity disorder (ADHD), and variable behavioral abnormalities. It is caused by heterozygous variant in the TNRC6B gene (NM_001162501.2, MIM 610740), which encodes the trinucleotide repeat-containing adaptor 6B protein. METHODS: In this study, two Chinese patients with TNRC6B deficiency syndrome were recruited, and genomic DNA extraction from peripheral blood leukocytes of these parents and their family members was extracted for whole-exome sequencing and Sanger sequencing. RESULTS: Here, we report two unrelated Chinese patients diagnosed with TNRC6B deficiency syndrome caused by novel de novo likely pathogenic or pathogenic TNRC6B variants c.335C>T (p.Pro112Leu) and c.1632delC (p.Leu546fs*63), which expands the genetic spectrum of TNRC6B deficiency syndrome. The clinical features of the patients were DD/ID, delayed speech, ADHD, behavioral abnormalities, short stature, low body weight, café-au-lait spots, metabolic abnormalities, and facial dysmorphism including coarse facial features, sparse hair, frontal bossing, hypertelorism, amblyopia, strabismus, and downslanted palpebral fissures, which expands the phenotype spectrum associated with TNRC6B deficiency syndrome. CONCLUSION: This study expands the genotypic and phenotypic spectrum of TNRC6B deficiency syndrome. Our findings indicate that patients with TNRC6B deficiency syndrome should be monitored for growth and metabolic problems and therapeutic strategies should be developed to address these problems. Our report also suggests the clinical diversity of TNRC6B deficiency syndrome.

Unraveling the genetic architecture of congenital vertebral malformation with reference to the developing spine.

Congenital vertebral malformation, affecting 0.13-0.50 per 1000 live births, has an immense locus heterogeneity and complex genetic architecture. In this study, we analyze exome/genome sequencing data from 873 probands with congenital vertebral malformation and 3794 control individuals. Clinical interpretation identifies Mendelian etiologies in 12.0% of the probands and reveals a muscle-related disease mechanism. Gene-based burden test of ultra-rare variants identifies risk genes with large effect sizes (ITPR2, TBX6, TPO, H6PD, and SEC24B). To further investigate the biological relevance of the genetic association signals, we perform single-nucleus RNAseq on human embryonic spines. The burden test signals are enriched in the notochord at early developmental stages and myoblast/myocytes at late stages, highlighting their critical roles in the developing spine. Our work provides insights into the developmental biology of the human spine and the pathogenesis of spine malformation.

Diagnosis of musculoskeletal abnormalities based on improved lightweight network for multiple model fusion.

This paper introduces a solution to address the intricacy of the model employed in the deep learning-based diagnosis of musculoskeletal abnormalities and the limitations observed in the performance of a single deep learning network model. The proposed approach involves the integration of an improved EfficientNet-B2 model with MobileNetV2, resulting in the creation of FusionNet. First, EfficientNet-B2 is combined with coordinate attention (CA) to obtain CA-EfficientNet-B2. Furthermore, aiming to minimize the model parameter count, we further enhanced the mobile inverted residual bottleneck convolution module (MBConv) employed for feature extraction in EfficientNet-B2, resulting in the development of CA-MBC-EfficientNet-B2. Next, the features extracted from CA-MBC-EfficientNet-B2 and MobileNetV2 are fused. Finally, the final diagnosis of musculoskeletal abnormalities was performed by using fully connected layers. The experimental results demonstrate that, first, compared to EfficientNet-B2, CA-MBC-EfficientNet-B2 not only significantly improves the diagnostic performance of musculoskeletal abnormalities, it also reduces the parameter count and storage space by 17%. Moreover, as compared to other models, FusionNet demonstrates remarkable performance in the area of anomaly diagnosis, particularly on the elbow dataset, achieving a precision of 92.93%, an AUC of 93.89% and an accuracy of 87.10%.

Morphological analysis of isolated hemivertebra: radiographic manifestations related to the severity of congenital scoliosis.

PURPOSE: The natural history of congenital scoliosis (CS) caused by hemivertebra varies greatly. This study aimed to explore the association between the morphology of hemivertebra and the severity of CS, since the diagnosis of the hemivertebra. METHODS: Patients with isolated (single fully segmented) hemivertebra were enrolled. The degree and progression of deformity were compared by three morphological parameters of hemivertebra, comprising whether the width of hemivertebra extends across the central vertical line of lower adjacent vertebra (midline); the lateral height ratio (LHR, lateral height of hemivertebra× 2/(lateral height of HV-1 plus HV + 1) with the cut-point being 0.9; and the sagittal position of hemivertebra that was divided into the lateral and posterolateral group. RESULTS: In total, 156 patients (mean age 9.7 ± 6.2 years, 81 males) were enrolled. The number of thoracic, thoracolumbar (T12/13-L1), and lumbar hemivertebrae were 63, 41, and 52, respectively. Hemivertebrae across the midline had larger scoliosis and kyphosis (58.3 ± 20.6° vs. 42.8 ± 15.0°, P <  0.001; 45.1 ± 32.5° vs. 29.5 ± 25.7°, P = 0.013, respectively). Hemivertebrae with LHR ≥0.9 was associated with larger scoliosis (55.7 ± 20.6° vs. 41.4 ± 13.3°, P <  0.001). Larger scoliosis and kyphosis were observed in posterolateral hemivertebrae (54.4 ± 21.0° vs. 44.4 ± 15.6°, P = 0.026; 51.4 ± 31.5° vs. 20.6 ± 17.1°, P <  0.001, respectively). Co-occurrence of more than one of the three positive parameters above indicated higher annual progression (5.0 ± 2.2° vs. 3.3 ± 1.3°, P <  0.001). CONCLUSION: Three positive parameters, width across the midline, LHR ≥0.9, and posterolateral position were associated with a more severe deformity in patients with isolated hemivertebra. Hemivertebrae with more than one positive parameter may cause progressive deformity, and thus need prompt surgery. LEVEL OF EVIDENCE: Prognostic, level IV.

Analysis of Spinopelvic Parameters and Lumbar Lordosis in Patients with Transitional Lumbosacral Vertebrae, with Special Reference to Sacralization and Lumbarization.

BACKGROUND: Transitional lumbosacral vertebra presents in 2 forms based on its origin: sacralization and lumbarization. These patients have 2 options for sacral endplates (upper and lower) and consequently, 2 sets of values for spinopelvic parameters and lumbar lordosis (LL). This study aimed to evaluate these parameters in asymptomatic patients with sacralization and lumbarization and compare them with each other and normative values. METHODS: Spinopelvic parameters and LL according to upper and lower endplate were measured using abdominal computed tomography in 1420 asymptomatic patients, of which 108 had Transitional lumbosacral vertebra. These parameters were compared among patients with lumbarization and sacralization and with normal controls. In addition, correlations between the upper and lower endplate parameters were determined. RESULTS: As compared to the control group, upper endplate measurements yielded lower spinopelvic parameters and LL values while lower endplate values yielded higher values. While these values were significantly different from normative values, these parameters were similar in both lumbarization and sacralization groups. Furthermore, most spinopelvic parameters of both upper and lower endplates were strongly correlated, and the differences between the upper and lower PI and LL values are relatively constant (27° and 14°, respectively. CONCLUSIONS: Upper and lower endplate parameters are comparable in patients with sacralization and lumbarization; therefore, the average spatial position of a sacralized L5 and a lumbarized S1 within the pelvis is similar and either parameter can be used for radiological measurements. Further studies with symptomatic patients are warranted to confirm these results.

Muscle abnormalities worsen after post-exertional malaise in long COVID.

A subgroup of patients infected with SARS-CoV-2 remain symptomatic over three months after infection. A distinctive symptom of patients with long COVID is post-exertional malaise, which is associated with a worsening of fatigue- and pain-related symptoms after acute mental or physical exercise, but its underlying pathophysiology is unclear. With this longitudinal case-control study (NCT05225688), we provide new insights into the pathophysiology of post-exertional malaise in patients with long COVID. We show that skeletal muscle structure is associated with a lower exercise capacity in patients, and local and systemic metabolic disturbances, severe exercise-induced myopathy and tissue infiltration of amyloid-containing deposits in skeletal muscles of patients with long COVID worsen after induction of post-exertional malaise. This study highlights novel pathways that help to understand the pathophysiology of post-exertional malaise in patients suffering from long COVID and other post-infectious diseases.

Extended phenotypic characterization of a novel Helsmoortel-van der Aa syndrome case series.

The neurodevelopmental disorder known as Helsmoortel-van der Aa syndrome (HVDAS, MIM#616580) or ADNP syndrome (Orphanet, ORPHA:404448) is a multiple congenital anomaly (MCA) condition, reported as a syndrome in 2014, associated with deleterious variants in the ADNP gene (activity-dependent neuroprotective protein; MIM*611386) in several children. First reported in the turn of the century, ADNP is a protein with crucial functions for the normal development of the central nervous system and with pleiotropic effects, explaining the multisystemic character of the syndrome. Affected individuals present with striking facial dysmorphic features and variable congenital defects. Herein, we describe a novel case series of HVDAS Italian patients, illustrating their clinical findings and the related genotype-phenotype correlations. Interestingly, the cutaneous manifestations are also extensively expanded, giving an important contribution to the clinical characterization of the condition, and highlighting the relation between skin abnormalities and ADNP defects.

Three-column osteotomy in long constructs has lower rates of proximal junctional kyphosis and better restoration of lumbar lordosis than anterior column realignment.

PURPOSE: Three-column osteotomies (TCOs) and minimally invasive techniques such as anterior column realignment (ACR) are powerful tools used to restore lumbar lordosis and sagittal alignment. We aimed to appraise the differences in construct and global spinal stability between TCOs and ACRs in long constructs. METHODS: We identified consecutive patients who underwent a long construct lumbar or thoracolumbar fusion between January 2016 and November 2021. "Long construct" was any construct where the uppermost instrumented vertebra (UIV) was L2 or higher and the lowermost instrumented vertebra (LIV) was in the sacrum or ileum. RESULTS: We identified 69 patients; 14 (20.3%) developed PJK throughout follow-up (mean 838 days). Female patients were less likely to suffer PJK (p = 0.009). TCO was more associated with open (versus minimally invasive) screw/rod placement, greater number of levels, higher UIV, greater rate of instrumentation to the ilium, and posterior (versus anterior) L5-S1 interbody placement versus the ACR cohort (p < 0.001, p < 0.001, p < 0.001, p < 0.001, p = 0.005, respectively). Patients who developed PJK were more likely to have undergone ACR (12 (32.4%) versus 2 (6.3%, p = 0.007)). The TCO cohort had better improvement of lumbar lordosis despite similar preoperative measurements (ACR: 16.8 ± 3.78°, TCO: 23.0 ± 5.02°, p = 0.046). Pelvic incidence-lumbar lordosis mismatch had greater improvement after TCO (ACR: 14.8 ± 4.02°, TCO: 21.5 ± 5.10°, p = 0.042). By multivariate analysis, ACR increased odds of PJK by 6.1-times (95% confidence interval: 1.20-31.2, p = 0.29). CONCLUSION: In patients with long constructs who undergo ACR or TCO, we experienced a 20% rate of PJK. TCO decreased PJK 6.1-times compared to ACR. TCO demonstrated greater improvement of some spinopelvic parameters.

Concomitant Thoracic Spinal Dural Arteriovenous Fistula and Spinal Cavernous Malformation.

Both spinal dural arteriovenous fistula (SDAVF) and spinal cavernous malformation (SCM) are uncommon vascular malformations. To our knowledge, such a case of SDAVF concomitant with SCM has not been reported. We encountered a case of a 55-year-old man who had weakness and numbness in both lower extremities. Magnetic resonance imaging showed a round-shape lesion identified as a cavernous malformation in the middle segment of the thoracic spine, with spinal edema and obvious flow voids. Diagnostic angiography revealed an SDAVF fed by the right T7 radicular artery with venous drainage. The intramedullary venous hypertension due to fistula was suspected of inducing the formation of SCM. This case may provide new insight into the pathogenesis of SCM.

Evaluation of congenital rib anomalies with multi-detector computed tomography in the Turkish population.

BACKGROUND: This study aimed to evaluate the congenital anomalies of ribs in the Turkish population using multi-detector computed tomography (CT) and to reveal the prevalence and distribution of these anomalies according to sexes and body sides. MATERIALS AND METHODS: This study included 1120 individuals (592 male, 528 female) over 18 who presented to our hospital with a suspicion of COVID-19 and who had thoracic CT. Anomalies such as a bifid rib, cervical rib, fused rib, Srb anomaly, foramen rib, hypoplastic rib, absent rib, supernumerary rib, pectus carinatum, and pectus excavatum, which were previously defined in the literature, were examined. Descriptive statistics were performed with the distribution of anomalies. Comparisons were made between the sexes and body sides. RESULTS: A prevalence of 18.57% rib variation was observed. Females had 1.3 times more variation than males. Although there was a significant difference in the distribution of anomalies by sex (p = 0.000), there was no difference in terms of body side of anomaly (p > 0.05). The most common anomaly was the hypoplastic rib, followed by the absence of a rib. While the incidence of the hypoplastic rib was similar in females and males, 79.07% of the absent ribs was seen in females (p < 0.05). The study also includes a rare case of bilateral first rib foramen. At the same time, this study includes a rare case of rib spurs extending from the left 11th rib to the 11th intercostal space. CONCLUSIONS: This study demonstrates detailed information about congenital rib anomalies in the Turkish population, which may vary between people. Knowing these anomalies is essential for anatomy, radiology, anthropology, and forensic sciences.

Immune skeletal dysplasia with neurodevelopmental abnormalities caused by a novel variant of EXTL3 gene in a Chinese family.

BACKGROUND: Immune skeletal dysplasia with neurodevelopmental abnormalities (ISDNA) is an extremely rare, autosomal recessive genetic disorder characterized by various skeletal abnormalities, neurodevelopmental deficits, and abnormal immune system function. ISDNA is caused by variation in the exostosin-like 3 (EXTL3) gene, located on chromosome 8p21.2, whose primary function is the biosynthesis of heparan sulfate (HS) skeleton structure. Only a few variations in the EXTL3 gene have been discovered so far. In these years of development, many pathogenic variants in genetic diseases with genetic and phenotypic heterogeneity have been investigated using whole-exome sequencing (WES) technology. METHODS: In this research, a novel EXTL3 variant was first detected in a patient using WES, which was validated from Sanger sequencing in this family. Family history and clinical information were then collected through comprehensive medical examinations and genetic counseling. In silico prediction was then utilized to confirm the pathogenicity of the variant. RESULTS: A novel homozygous variant, NM_001440: c.2015G>A (p.Arg672Gln) in the EXTL3 gene, was identified using WES, which has never been reported before. Sanger sequencing was performed to confirm that the variant segregated with the disease within the family. CONCLUSION: This research identified a novel pathogenic variant in the EXTL3 gene responsible for ISDNA in a Chinese family. It showed the potential diagnostic role of WES in ISDNA, expanded the EXTL3 gene variation spectrum, and demonstrated that the diagnosis of ISDNA using WES is feasible and effective. More comprehensive genetic counseling and precise prenatal diagnosis for the next pregnancy can also be provided to families with genetic disorders.