Skeletal Abnormalities Research Articles

Understanding complex begins with knowing the simple

Diagnosing rare genetic disorders is clinically challenging. Patients undergo extensive investigations, including multiple genetic/genomic tests. Despite being seen by several specialists, they often remain without a genetic diagnosis. A 4-year-old female with consanguineous parents presents with skeletal abnormalities, dysmorphism, global developmental delay, slow growth, and recurrent severe systemic infections. Initial next generation sequencing based primary immunodeficiency gene panel and SNP microarray detected no causative pathogenic variants. The final diagnosis was possible only following a special cytogenetic test, C-banded karyotype, which revealed heterochromatin repulsion and premature centromere separation in all metaphases, suggestive of Roberts syndrome (RS). RS/ESCO2-spectrum disorder is a rare autosomal recessive disorder caused by biallelic loss of function variants in the ESCO2 gene, with only 150 cases reported to date. Microarray analysis also showed long contiguous stretches of homozygosity at the 8p21 locus, which encompasses the ESCO2 gene. ESCO2 gene sequencing was recommended for molecular confirmation of the diagnosis. This case illustrates the importance of appropriate selection of genomic tests and highlights the critical role of karyotyping (including the use of specialized stains) in the diagnosis of some rare genetic disorders.

Could primary hyperparathyroidism develop in cases with neurofibromatosis type-1-associated pheochromocytoma: Two cases with pheochromocytoma gene panel analysis

Abstract Introduction Neurofibromatosis type-1 (NF-1) is an autosomal dominant genetic disorder. It is associated with the development of café-au-lait macules, axillary and/or inguinal frecklings, Lisch nodules, hypertension, osteoporosis, skeletal abnormalities, as well as benign and malignant tumors, such as optic gliomas, peripheral nerve sheet tumors, and rarely, pheochromocytomas. However, primary hyperparathyroidism is rarely documented in patients with bilateral pheochromocytomas associated with NF-1 and is typically linked to MEN-2 A syndrome. Here we present two cases of NF-1-associated bilateral pheochromocytomas who developed primary hyperparathyroidism during follow-up. Clinical case In 2010, diagnostic ultrasonography performed for abdominal pain in a 60-year-old female patient revealed an adrenal mass. Multiple neurofibromas, axillary freckling, café-au-lait macules, and lisch nodules were found on physical examination (Figure 1A, B, C, and D). A diagnosis of pheochromocytoma was confirmed by high urine metanephrines and a hyperintense, 35 x40 mm mass on T2 weighted MRI sequences. The patient underwent right adrenalectomy. One year later, a diagnosis of primary hyperparathyroidism was made based on the high serum levels of calcium and intact PTH, and low serum phosphorus levels (Table-1). Radiotracer uptake was seen on a parathyroid MIBI scan in the thyroid's right inferior area. During follow-up, a 50×51 mm mass, hyperintense on T2 weighted MRI sequences was discovered on the left adrenal gland (figure 1-E). A diagnosis of pheochromocytoma was confirmed by detecting high plasma metanephrine and normetanephrine levels. The patient underwent left adrenalectomy 5 years following the initial diagnosis. Clinical case A 64-year-old female patient was admitted due to recently developed hypercalcemia. She had previously undergone two successive adrenalectomies, 4 years apart in 1999 and 2003, and was confirmed to have bilateral pheochromocytomas by histopathological analysis. Multiple neurofibromas, axillary freckling, café-au-lait macules, and Lisch nodules were found on physical examination. A diagnosis of primary hyperparathyroidism was made by detecting high serum calcium, intact parathormone, and low serum phosphorus levels. The patient underwent a right parathyroidectomy in 2012. In both cases, a panel analysis of pheochromocytoma gene mutations was carried out. In cases 1 and 2, a heterozygous nonsense mutation (17q11.2, C.2023G>T (P.G675*) and a non-frameshift deletion (17q11.2 c.5036) in the NF-1 gene were respectively found. Both instances tested negative for genetic alterations for RET, FH, MAX, SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM-127, and VHL. Conclusion The development of primary hyperparathyroidism in these two cases of pheochromocytomas associated with genetically confirmed NF-1 raises the possibility that primary hyperparathyroidism may develop in patients with NF-1-associated pheochromocytoma.

Effects of Rapid Maxillary Expansion on Upper Airway Volume in Growing Children: A Three-Dimensional Cone-Beam Computed Tomography Study.

Background: Rapid maxillary expansion (RME) is a common orthodontic procedure that widens the maxillary arch to treat moderate to mild overcrowding and transverse skeletal and dental abnormalities. Orthodontic equipment applies lateral tension on posterior maxilla teeth or palate mucosa to the mid-palatal suture. The maxilla may grow transversely when force is applied at right angles to the mid-palatal suture, which is usually inactive in children and adolescents. This study used cone-beam computed tomography (CBCT) and an authorized upper respiratory airway volume measurement approach to compare RME cohort pharyngeal airway volume changes to healthy controls. Materials and Methods: This retrospective analysis included 52 RME patients and 52 healthy controls. The RME category's expansion regimen entailed twisting the screw of expansion on a tooth-attached Hyrax-type expansion equipment by 0.25 mm daily for at least 14 days. After six months, a few RME participants used fixed orthodontic gear. The comparison group used fixed orthodontic appliances for minor malocclusions without extractions (without RME). CBCT scans from 1021 orthodontic patients who visited a dental hospital between 2012 and 2022 were examined. The registry comprised only anonymized photographs. Volume, minimum cross-sectional area (MCA), molar width, and inter-molar width were measured before and after therapy. Results: The control group had 12227.12 mm3 at T0 and 15805.54 mm3 at T1. The control group's T0-T1 volume difference was statistically significant (p = 0.007). The RME group has 12884.84 mm3 at T0 and 17471.08mm3 at T1. The RME group had a significant volume difference at T0 and T1 (p = 0.002). The volume RME effect was ±1011.92and statistically insignificant. (p > 0.05). MCA in the control group was 126.04 mm2 at T0 and 170.61 mm2at T1. MCA at T0 and T1 in the control group was statistically significant (p = 0.041). RME group MCA was 126.53 mm3 at T0 and 164.69 mm2 at T1. The RME group had a significant volume difference at T0 and T1 (p = 0.002). The MCA, RME effect was 5.92 and statistically insignificant (p > 0.05). Both the control and RME groups had statistically significant volume and MCA differences at T0 and T1. However, the intergroup analysis showed no significant differences across the groups. Conclusion: Tooth-borne RME does not affect upper airway or MCA volume in children compared to controls. Upper airway changes were better with younger skeletal ages before treatment. The findings may aid RME for young children.

Difficult situation in treatment of medullary thyroid carcinoma in patient with multiple endocrine neoplasia type 2 B(MEN2B)

Abstract Introduction Multiple endocrine neoplasia type 2B (also known as ‘MEN2B’,‘Multiple endocrine neoplasia type 3′ or ‘Wagenmann–Froboese syndrome’) is a genetic disease characterized by the presence of medullary carcinoma of the thyroid, pheochromocytoma, mucosal neuromas, marfanoid features and multiple skeletal abnormalities such as kyphoscoliosis and pes cavus. Clinical Case A 16 years male presented with neck swelling and dysmorphic feature in the form of marfanoid habitus, including multiple tongue and oral mucosal swelling with mucosal neuromas on the anterior third of the tongue, the lips and the inner eyelid. Lips are thickened and bumpy. Visible neck swelling, palpable solid neck mass, high arm span to height ratio at >1.05, elongated fingers, pes cavus and positive wrist sign which is defined as when the distal phalanges of the thumb and fifth finger overlap on encircling the opposite wrist, were present. Ultrasound of the neck revealed a left solid irregular mass (57mmx33mm), that is hypoechoic, has coarse calcification, hypervascularity, that is mostly central, Multiple cervical lymph node(abnormal nodes include shape (round), absent hilum, intranodal necrosis, reticulation, calcification, peripheral vascularity),Investigation at beginning, Normal thyroid function test and biochemical and electrolyte were observed, Chest x ray was normal, FNAC done for thyroid nodule that showed multiple clumps of large hyperchromatic oval cells picture suggesting high suspicion of thyroid malignancy, thyroid biopsy advised, The patient was referred the FDEMC center for further evaluation and investigation prior to the surgery. During investigation at FDEMC center, thyroid function test normal, biochemistry normal, including PTH and electrolytes, Calcitonin was very high 465 pg/mL (0.2–27.7 pg/mL),GH under GTT was normal, IGF 1 182µg/L (150–350),Plasma metanephrine 40 pg/ml(<90pg/ml),and Plasma normetanephrine 27pg/ml(<196pg/ml) were normal. The patient referred to surgery, total thyroidectomy with radical neck dissection with multiple lymph node resection was performed. The biopsy revealed medullary thyroid carcinoma with cervical lymph node secondaries (bilateral multiple foci in both lobes). The patient kept on levothyroxine tab 100mcg.The follow up of the patient after one month by ultrasound and calcitonin level revealed residual thyroid tissue and two large cervical LN in the the ultrasound and a calcitonin level of 322 pg/mL Another surgical neck dissection to the metastatic LN <multiple LN 7×5cm, multiple suprasternal mass dissection 3×2.5cm,remnant of thyroid tissue 0.8cm,Follow up the patient after one month by ultrasound and calcitonin level still showed that there is residual pathological cervical LN, while the calcitonin level still high 412 pg/mL. PET scan done for him showed there is uptake in the head, neck and chest. The calcitonin was repeatedly was high.

A rare case of concomitant hypophosphatemic osteomalacia and neurofibromatosis type 1

Abstract Introduction Neurofibromatosis type 1 is a rare genetic disorder with an increased susceptibility to develop skeletal abnormalities. However, the association of hypophosphatemic osteomalacia and neurofibromatosis type 1 is extremely rare. Herein, we report a case of hypophosphatemic osteomalacia in concomitant with neurofibromatosis type 1. Clinical Case A 45-year-old Turkish female patient, who was followed up in another hospital due to osteoporosis and kyphoscoliosis, applied to us with the complaints of persistent bone pain and inability to walk. She had no chronic diseases other than osteoporosis. The physical examination revealed widespread freckling over her trunk and proximal parts of upper and lower extremities and multiple neurofibromas and cafe au lait spots all over her body (figure 1). It was learned that her 2 brothers, mother and daughter also had the widespread freckling. They have no known chronic diseases. She had a severe degree of kyphoscoliosis. She had not have any complaints up to 24 years of age, and low back pain started after delivery. She was diagnosed with osteoporosis at the age of 29. In about 15 years, her height decreased from 167 cm to 135 cm. She had a severe degree of kyphoscoliosis and severe bone pain and was unable to walk on her own because of pain. Bilateral ophthalmic examination revealed no Lisch nodules. Audiometer revealed no abnormalities. Laboratory findings were as follows: Ca: 9.4 (8.4–10.6 mg/dl), phosphorus: 1.8 (2.3–4.7 mg/dl), albumin: 4.2 g/dl, parathormone: 88.3 (11–80 pg/ml), 25 hydroxy vitamin D: 26.1 ug/L, creatinine: 0.4 mg/dl, alkaline phosphatase: 79 (35–105 U/L), the 24-hour urinary excretion of calcium: 187.5 mg/24 h, the 24-hour urinary excretion of phosphorus: 253 mg/24 h, fractional excretion of phosphate: %8.5 and maximum transport of phosphorus in the renal proximal tubules (TmP/GFR): 0.74 (0.88–1.42 mmol/L). According to laboratory data there was a hyperphosphaturia. On the basis of the physical examination, laboratory and radiological findings, she was diagnosed with neurofibromatosis type 1 and hypophosphatemic osteomalacia. Oral phosphate solution (1.5 gram as elemantary phosphorus per day in 3 divided doses) and calcitriol (1 microgram per day in 2 divided doses) were started. After 6 months of therapy, bone pain was significantly decreased and her serum phosphorus level increased. The results of genetic analysis are awaited. Conclusion The coexistence of hypophosphatemic osteomalacia and neurofibromatosis type 1 have been reported in less than 50 cases in the literature. The underlying mechanism is not clarified. The diagnosis of hypophosphatemic osteomalacia should be kept in mind in patients with neurofibromatosis type 1, as they will benefit greatly from oral phosphorus solution and active vitamin D.

A tapt1 knock-out zebrafish line with aberrant lens development and impaired vision models human early-onset cataract.

Bi-allelic mutations in the gene coding for human trans-membrane anterior-posterior transformation protein 1 (TAPT1) result in a broad phenotypic spectrum, ranging from syndromic disease with severe skeletal and congenital abnormalities to isolated early-onset cataract. We present here the first patient with a frameshift mutation in the TAPT1 gene, resulting in both bilateral early-onset cataract and skeletal abnormalities, in addition to several dysmorphic features, in this way further expanding the phenotypic spectrum associated with TAPT1 mutations. A tapt1a/tapt1b double knock-out (KO) zebrafish model generated by CRISPR/Cas9 gene editing revealed an early larval phenotype with eye malformations, loss of vision, increased photokinetics and hyperpigmentation, without visible skeletal involvement. Ultrastructural analysis of the eyes showed a smaller condensed lens, loss of integrity of the lens capsule with formation of a secondary lens and hyperplasia of the cells in the ganglion and inner plexiform layers of the retina. Transcriptomic analysis pointed to an impaired lens development with aberrant expression of many of the crystallin and other lens-specific genes. Furthermore, the phototransduction and visual perception pathways were found to be significantly disturbed. Differences in light perception are likely the cause of the increased dark photokinetics and generalized hyperpigmentation observed in this zebrafish model. In conclusion, this study validates TAPT1 as a new gene for early-onset cataract and sheds light on its ultrastructural and molecular characteristics.

2D shear wave elastography of the rectus femoris muscle in patients with cirrhosis: Feasibility and clinical findings. A pilot study

Background and aimsFrailty is frequent in cirrhosis and associated with skeletal muscle abnormalities and worse prognosis. 2D shear-wave elastography (2D-SWE) could mirror biomechanical properties of skeletal muscle reflecting muscle quality. However, there is no data on 2D-SWE on skeletal muscle stiffness assessment in cirrhosis and on frailty. MethodsOutpatients with cirrhosis were prospectively included in a single center. Skeletal muscle stiffness was studied at the rectus femoris by 2D-SWE. Ileo-psoas area and index (area/height2), and antero-posterior diameter of rectus femoris (RF) was measured on ultrasound. ResultsWe included 44 patients (24 male, age 59 [IQR 49–66]) with a median liver frailty index (LFI) of 3.7 (IQR 3.2–4.0). Measurement of RF muscle stiffness (RFMS) was feasible in all with high inter-measurement reproducibility. RFMS did not correlate with LFI, liver function and skeletal muscle diameters. Ileo-psoas index was lower in frail patients (1.7 vs 1.0 cm2/m2, p = 0.024). RF antero-posterior diameter inversely correlated with LFI (r -0.578: p<0.001). ConclusionRFMS by 2D-SWE is feasible and reproducible in cirrhosis and is independent of liver function and LFI, and warrants further studies in this setting. RF antero-posterior diameter could be reported as an objective parameter mirroring sarcopenia and frailty.

Use of Computed Tomography in Evaluation and Management of Shell Fracture in a Red Eared Slider Turtle ( Trachemys scripta elegans) A Case report

Traumatic lesions of the shell are common problems in chelonians. Lesions of the shell vary in severity from a simple superficial abrasion (with a loss of the external skin layer and exposure of the bone) to complicated fractures of the carapace with exposure of internal organs of the coelom and injury of the soft tissues (Barten, 2006). In most shell or skeletal injuries in the turtle, plain radiographic data do not reveal the extent of complex fractures due to superimposed bone structures (Abou-Madi et al., 2002). In Comparison with conventional radiography, computed tomography (CT) allows better distinction of specific tissue densities and discrete changes in organ size, shape, margin, contour and position (Gaudron et al., 2001). Computed tomography is a non-invasive, cross-sectional diagnostic imaging technique that offers significant advantages for detection of pathologies in chelonians, and is ideal for diagnosing skeletal and soft tissue abnormalities (Gumpenberger and Henninger, 2001). The aim of the present work was to evaluate the three dimensional computed tomography (CT) for clinical examination of shell lesions in a red eared slider turtle.

Modulatory effect of ginger on skeletal malformations, cell cycle, apoptosis and structural changes in the liver of rat fetuses prenatally exposed to labetalol

BackgroundDrug-induced liver damage with clinical symptoms has been related to labetalol in a number of instances. In addition to having a wide range of anti-inflammatory and antioxidant qualities, ginger also includes biotrace that are crucial in the fight against disease and skeletal deformity. In this study, we hypothesized that prenatal supplementation of ginger (200 mg/kg) attenuates skeletal malformation and hepatotoxicity mediated by labetalol during the organogenesis period. The tested dams were divided into four groups: control, ginger (200 mg/kg), labetalol (300 mg/kg) and combined group (labetalol and ginger at the same doses).ResultsThe labetalol group showed various skeletal abnormalities represented by mandibular hypoplasia, costal separation and retardation in the ossification. Histological and ultrastructural examination of the fetal liver tissue revealed multiple pathological changes. DNA damage, G0/G1 cell cycle arrest and a high percentage of apoptosis were also detected in the fetal hepatocytes from labetalol groups through gel electrophoresis and flow cytometry using PI and annexin V/PI methods, respectively. Administration of ginger after labetalol caused an evident decrease in these skeletal malformations, structural changes, DNA damage, apoptosis and G0/G1 cell cycle arrest.ConclusionsIt can be concluded that ginger has great potential in attenuating the skeletal malformation, structural changes and cyto-genotoxicity of fetal hepatocytes upon prenatal exposure to labetalol.

Primary immunodeficiency in a patient with Kabuki syndrome

Kabuki syndrome is a well-known disease characterized by postnatal growth failure, dysmorphic facial features, skeletal abnormalities, and mental retardation associated with one of the pathogenic mutations in the KMT2D or KDM6A genes. At least 50% of individuals with Kabuki syndrome tend to develop recurrent infections and immune abnormalities, primarily hypogammaglobulinemia. The article describes the clinical course of resistant infectious syndrome in an 18-month-old child without typical dysmorphic and dermatoglyphic manifestations characteristic of Kabuki syndrome. A long history of resistant bacterial infection, enterocolitis, microcephaly, autistic-like behavior, hyperkinetic disorder, CT scan patterns of granulomatous lymphocytic interstitial lung disease (GLILD), suggested the immunodeficiency as part of a hereditary genetically determined syndrome. At the same time, the patient did not experience hypogammaglobulinemia characteristic of Kabuki syndrome. The upper normal response to previously received vaccination and a polyclonal repertoire of B-lymphocytes indicated the absence of disturbances in the humoral immunity. Immunophenotyping revealed the absence of T-regulatory cells (CD4+CD25++CD127–) as well as effector NK cells (CD16+CD56+CD3–) in the peripheral blood. The significant reduction of CD4+CD3+ T-lymphocytes and CD4+/CD8+ index was observed. In addition, no expression of integrin-beta (CD18) on neutrophils revealed.Conclusion. In children under the age of 2, Kabuki syndrome may present difficulties for clinical diagnosis due to the absence of distinctive phenotypic signs. Patients with mental disorders, congenital malformations, recurrent infections suspected of immunodeficiency should be carried out using molecular genetic exploration, including testing for mutations in the KMT2D and KDM6A.

Age-related perceptions of laypeople on Class II facial profile alterations

Objectives: The treatment plan for young patients with skeletal abnormalities is often selected by their parents. However, the treatment outcome should correspond with the patient’s preference to reduce the treatment need in the future. This study aimed to investigate the influence of post-treatment facial profiles in a skeletal Class II female subject on esthetic perceptions by laypeople of different age groups. Material and Methods: Seven digitally adjusted profile images of predetermined nasolabial angle (NLA) and facial contour angle (FCA) were obtained from a female with skeletal Class II. These profile images were evaluated by 180 laypeople and were stratified according to three age groups (12–15, 22–32, and 44–54 years) using a visual analog scale and ranking order. Results: The slightly convex profile with normal NLA (11° FCA and 91° NLA) was the most preferred by all age groups. The convex profile with the largest NLA (17° FCA and 115° NLA) was the least preferred by age group 12–15 and 44–54 years and the convex profile with normal NLA (17° FCA and 91° NLA) was the least preferred by age group 22–32 years. Sex was found to be significantly related to the rating score with females rated higher scores. Conclusion: The most attractive profile for all three age groups was a mandibular advancement-simulating profile. The least attractive profile for age groups 12–15 and 44–54 years was a most camouflage-simulating profile, while the least attractive profile for age group 22–32 years was an untreated most pronounced Class II profile.

Next generation phenotyping with quantitative narration for DEGCAGS syndrome.

The diagnosis of rare Mendelian disorders usually relies upon the interpretation of prose and is complicated by a lack of objective, reproducible phenotypic data. To address this limitation, we developed a next generation phenotyping workflow to phenotypically characterize developmental delay with gastrointestinal, cardiovascular, genitourinary, and skeletal abnormalities (DEGCAGS). We identified 15 people affected with DEGCAGS, including one novel patient identified at our hospital and 14 patients previously reported in the literature. Human Phenotype Ontology (HPO) terms were extracted from the patient chart and literature review. The HPO terms were sorted by count according to HPO hierarchy of terms. Phenotypes that cosegregate were identified utilizing a co-occurrence matrix. A quantitative narrative illustrated by violin plots was created for our patient from phenotypic data per each day of hospital admission. A total of 252 unique HPO terms were extracted from the patient record and literature review. The highest count of systemically sorted and unsorted terms and the most commonly co-occurring terms were described. A violin plot of phenotype occurrences demonstrated a progression of phenotypes over time. NGP offers a quantitative approach to phenotyping to generate phenotypic data in an objective and reproducible manner akin to NGS.

The Clinical and Molecular Spectrum of Trichorhinophalangeal Syndrome Types I and II in a Turkish Cohort Involving 22 Patients.

Trichorhinophalangeal syndrome is a rare autosomal dominant disorder characterized by distinctive craniofacial and skeletal abnormalities. This study aimed to delineate the trichorhinophalangeal syndrome phenotype and to compare the clinical and molecular findings between trichorhinophalangeal syndrome types I and II. A total of 22 trichorhinophalangeal syndrome patients aged 0.9-45 years from 17 families were enrolled. Nineteen patients were diagnosed with trichorhin ophalangeal syndrome I and 3 with trichorhinophalangeal syndrome II. Genetic analyses were made by TRPS1 sequencing and/or chromosomal microarray analyses. A novel frameshift variant (c.531_532del), a known missense variant, and whole-gene deletions were the pathogenic TRPS1 variants detected in trichorhinophalangeal syndrome I. Three trichorhinophalangeal syndrome II patients had large deletions with variable breakpoints involving the TRPS1-EXT1 interval. All patients had the typical craniofacial findings of trichorhinophalangeal syndrome such as a pear-shaped nose, long philtrum, and thin upper lip, as well as cone-shaped epiphyses. Sparse hair and eyebrows (20/22), short metacarpals and metatarsals (20/22), and small hands (19/22) were common. While craniofacial and limb abnormalities were similar in trichorhinophalangeal syndrome I and II, 3 of 19 trichorhinophal angeal syndrome I patients had mild, and 2 of 3 trichorhinophalangeal syndrome II patients had severe intellectual disability. Three trichorhinophalangeal syndrome II patients including the patient with the EXT1 deletion beginning from exon 2 had exostoses. In trichorhinophal angeal syndrome II, although microdeletion sizes and facial or skeletal features were not correlated, patients with larger deletions had severe intellectual disability. This study has expanded the existing knowledge on the phenotype-genotype spectrum in trichorhinophalangeal syndrome. We suggest including the EXT1 gene partially in the minimal critical region for trichorhinophalangeal syndrome II.

Stone Man Syndrome: A Rare and Debilitating Genetic Disorder with a Misguided Immune Response

Stone Man Syndrome, also known as Fibrodysplasia Ossificans Progressiva(FOP), is a rare genetic disorder characterized by progressive bone formation and connective tissue ossification. The condition affects approximately 1 in 2 million people worldwide and typically becomes apparent during early childhood. Individuals with Stone Man Syndrome experience the formation of extra bone in their muscles, tendons, and ligaments, which eventually leads to joint immobility and skeletal abnormalities. The condition progresses gradually and often leads to the fusion of the spinal column and rib cage, resulting in respiratory problems and limited mobility. FOP is caused by a mutation in the ACVR1 gene, which encodes a protein involved in bone formation and repair. The mutation leads to the activation of a specific signalling pathway, causing the body to produce excess bone tissue in response to injury or trauma. Currently, there is no cure for Stone Man Syndrome, and treatment options are limited. Physicians can only manage the symptoms of the condition and help patients maintain mobility through physical therapy, pain management, and surgery. However, surgery can be risky due to the risk of triggering new bone formation. The diagnosis of Stone Man Syndrome is typically based on clinical evaluation and genetic testing. Early diagnosis is critical to developing effective treatment plans and providing support for patients and their families. In conclusion, Stone Man Syndrome is a rare genetic disorder characterized by the progressive formation of extra bone tissue, leading to joint immobility and skeletal abnormalities. Although there is currently no cure for the condition, early diagnosis and management of symptoms can improve patients’ quality of life.

Intraoral and maxillofacial abnormalities in patients with autosomal dominant hyper-IgE syndrome.

Autosomal dominant hyper-IgE syndrome (AD-HIES) is an inborn error of immunity (IEI) caused by a dominant-negative mutation in the signal transducer and activator of transcription 3 (STAT 3). This disease is characterized by chronic eczematoid dermatitis, recurrent staphylococcal skin abscesses, pneumonia, pneumatoceles, and extremely high serum IgE levels. Loss-of-function STAT3 mutations may also result in distinct non-immunologic features such as dental, facial, skeletal, and vascular abnormalities, central nervous system malformations and an increased risk for bone fractures. Prophylactic treatment of Candida infections and prophylactic antimicrobial therapy for staphylococcal skin infections and sinopulmonary infections are essential. An awareness of the oral and maxillofacial features of HIES may facilitate early diagnosis with genetic counselling and may improve future patient care. This study describes oral, dental, and maxillofacial manifestations in 14 patients with genetically defined AD-HIES. We also review the literature and propose recommendations for the complex care of patients with this rare primary immunodeficiency.

Targeting Skeletal Muscle Dysfunction With L-Carnitine for the Treatment of Patients With Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is a major medical problem and the world's third leading cause of death. COPD is a chronic disease with heterogeneous clinical symptoms, disease progression, and treatment responses. Besides pulmonary symptomatology, the common systemic clinical manifestations are cachexia, muscle weakness, and widespread comorbidities such as cardiovascular diseases, diabetes, osteoporosis, and infections. The adverse effects of pharmaceutical therapies contribute to the difficulty of health risk assessment and management of COPD patients. This review shows how skeletal muscle dysfunction and metabolic abnormalities contribute significantly to COPD patients' symptoms, functional activities, quality of life, and overall disease outcomes. Based on the clinical evidence of L-carnitine and derivatives as metabolic and muscle bioenergetic enhancers, we propose broader research and implementation of this nutraceutical agent as an effective, inexpensive, and safe adjuvant therapeutic for the long-term management of COPD patients. Moreover, we believe the management of COPD as a chronic disease should be shifted from symptomatic reactive pharmaceutical intervention to more constructive and non-toxic approaches using a single or combination of natural and nutritional agents with potential muscle metabolic enhancing and immunomodulating activities to achieve a better overall outcome for the patients in terms of morbidity, mortality, and medical cost-reduction.

Ameliorative Effects of Bifidobacterium animalis subsp. lactis J-12 on Hyperglycemia in Pregnancy and Pregnancy Outcomes in a High-Fat-Diet/Streptozotocin-Induced Rat Model.

Bifidobacterium, a common probiotic, is widely used in the food industry. Hyperglycemia in pregnancy has become a common disease that impairs the health of the mother and can lead to adverse pregnancy outcomes, such as preeclampsia, macrosomia, fetal hyperinsulinemia, and perinatal death. Currently, Bifidobacterium has been shown to have the potential to mitigate glycolipid derangements. Therefore, the use of Bifidobacterium-based probiotics to interfere with hyperglycemia in pregnancy may be a promising therapeutic option. We aimed to determine the potential effects of Bifidobacterium animalis subsp. lactis J-12 (J-12) in high-fat diet (HFD)/streptozotocin (STZ)-induced rats with hyperglycemia in pregnancy (HIP) and respective fetuses. We observed that J-12 or insulin alone failed to significantly improve the fasting blood glucose (FBG) level and oral glucose tolerance; however, combining J-12 and insulin significantly reduced the FBG level during late pregnancy. Moreover, J-12 significantly decreased triglycerides and total cholesterol, relieved insulin and leptin resistance, activated adiponectin, and restored the morphology of the maternal pancreas and hepatic tissue of HIP-induced rats. Notably, J-12 ingestion ameliorated fetal physiological parameters and skeletal abnormalities. HIP-induced cardiac, renal, and hepatic damage in fetuses was significantly alleviated in the J-12-alone intake group, and it downregulated hippocampal mRNA expression of insulin receptor (InsR) and insulin-like growth factor-1 receptor (IGF-1R) and upregulated AKT mRNA on postnatal day 0, indicating that J-12 improved fetal neurological health. Furthermore, placental tissue damage in rats with HIP appeared to be in remission in the J-12 group. Upon exploring specific placental microbiota, we observed that J-12 affected the abundance of nine genera, positively correlating with FBG and leptin in rats and hippocampal mRNA levels of InsR and IGF-1R mRNA in the fetus, while negatively correlating with adiponectin in rats and hippocampal levels of AKT in the fetus. These results suggest that J-12 may affect the development of the fetal central nervous system by mediating placental microbiota via the regulation of maternal-related indicators. J-12 is a promising strategy for improving HIP and pregnancy outcomes.

Bone abnormalities in the middle Anisian marine sauropsids from Winterswijk.

While the occurrence of skeletal pathologies in Middle Triassic marine reptiles has been poorly documented until now, massive accumulations of bone remains from the Germanic Basin provide the opportunities for documentation. Herein, we describe skeletal abnormalities in the Middle Triassic bone material from the Vossenveld Formation of Winterswijk, the Netherlands. The aim of the study is to distinguish in the studied bones pathologies resulting from malady or trauma and taphonomic alterations. Furthermore, an attempt was made to assess on how the pathologies also represent paleoecological data. Our survey led to the identification of one broken and healed bone, one case of abnormal coossification, and one case of posttraumatic fibro-osseous dysplasia. While the latter two pathologies give little insight into the ecology and function of the affected animals, the fractured dentary is attributed to Nothosaurus marchicus, a common sauropterygian macropredator. It proves that the individual survived long enough to heal, despite the injury hampering its hunting potential. One abnormally shaped humerus is interpreted as postmortem taphonomic deformation, emphasizing the necessity of utilization of detailed diagnostics to distinguish actual paleopathologies from nonbiological distortion.

Perawatan dini pada displasia vertikal (Tinjauan Pustaka)

Vertical dysplasia in pediatric patients is divided into vertical overgrowth dysplasia and vertical growth deficiency dysplasia. Although it is still debated when to start treating vertical dysplasia, recently, there has been increasing interest in treating vertical dysplasia that sometimes accompanies cases of sagittal or transverse dysplasia. The clinical picture of vertical overgrowth dysplasia is generally manifested by a large anterior facial height, especially in the one-third anterior lower part of the face, sometimes accompanied by an anterior open bite. Treatment of children with vertical dysplasia, especially those with excessive vertical dysplasia, should be done early so the disorder does not get worse and can take advantage of the existing growth potential. Treatment of cases of vertical dysplasia must consider the nature of the abnormality, namely dental or skeletal abnormalities, morphological age, the direction of mandibular rotation, and the possibility of other dysplasia and existing etiological factors..

Genetic spectrum of CAKUT and risk factors for kidney failure: a pediatric multicenter cohort study.

Congenital anomalies of the kidney and urinary tracts (CAKUT) are the leading cause of kidney failure in children with phenotypic and genotypic heterogeneity. Our objective was to describe the genetic spectrum and identify the risk factors for kidney failure in children with CAKUT. Clinical and genetic data were derived from a multicenter network (Chinese Children Genetic Kidney Disease Database, CCGKDD) and the Chigene database. A total of 925 children with CAKUT who underwent genetic testing from 2014 to 2020 across China were studied. Data for a total of 584 children wereobtained from the CCGKDD, including longitudinal data regarding kidney function. The risk factors for kidney failure were determined by the Kaplan-Meier method and Cox proportional hazards models. A genetic diagnosis was established in 96 out of 925 (10.3%) children, including 72 (8%) with monogenic variants, 20 (2%) with copy number variants (CNVs), and 4 (0.4%)with major chromosomal anomalies. Patients with skeletal abnormalities were more likely to have large CNVs or abnormal karyotypes than monogenic variants. Eighty-two patients from the CCGKDD progressed to kidney failure at a median age of 13.0 (95% confidence interval, 12.4-13.6) years, and twenty-four were genetically diagnosed with variants of PAX2, TNXB, EYA1, HNF1B and GATA3 or the 48, XXYY karyotype. The multivariate analysis indicated that solitary kidney, posterior urethral valves, bilateral hypodysplasia, the presence of certain variants and premature birth were independent prognostic factors. The genetic spectrum of CAKUT varies among different subphenotypes. The identified factors indicate areas that require special attention.