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Objective To evaluate and explore the diagnosis, treatment, and clinical course of tuberous sclerosis complex(TSC)-associated hepatic angiomyolipoma (AML) and renal AML, emphasizing the limitations of genetic diagnostics and the significance of a multidisciplinary approach. Methods Utilizing comprehensive clinical data and multidisciplinary consultations, we thoroughly analyzed multiple genetic test results throughout the disease course. Following the confirmation of diagnosis, appropriate pharmacological treatment was administered, and its efficacy was evaluated.The patient was a 31-year-old male with a 12-year history of multiple atypical AMLs in the liver and kidneys. Multi-system manifestations included angiofibromas on the nose and perioral region, shagreen patches on the buttocks and cortical dysplasia found by head MRI. A history of dental enamel defects had been observing. Over theyears, the primary therapeutic approach has been performed as repeated surgical resections of AMLs. To further delineate the patient's genetic mutation profile and achieve a definitive diagnosis, we conducted a comprehensive genetic analysis. Results Through genetic analysis, a TSC2 c.2353C＞T(p.Gln785*) mutation with allele frequencies of 4.04% was identified in peripheral blood and 10.38% in tumor tissue, suggesting potential germline mosaicism originating during embryonic development. The patient was diagnosed with AML associated with TSC. Treatment with the mTOR inhibitor everolimus over one year resulted in a significant reduction in RAML lesions achieving partial remission. Conclusions It is imperative to consider the possibility of TSC in patients with AML. When TSC is diagnosed, meticulous scrutiny of low-frequency germline mutations is essential. mTOR inhibitors can be a treatment option for patients with TSC-AML.

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Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disease caused by mutations in the tumor suppressor genes TSC1 and/or TSC2. Its clinical manifestations include recurrent seizures, intellectual disability, and facial angiofibromas. Herein, we report the case of a patient with TSC who had recurrent seizures since childhood, shark skin nevus on the right occipital region, and multiple purple-red nodules on both cheeks. Computer tomography (CT) revealed multiple small calcifications around the lateral ventricles, pulmonary lymphangioleiomyomatosis, multiple renal angiomyolipomas, and multiple lipomatous lesions on the left ventricular wall. Through this case report, we aimed to improve the understanding of TSC.

Copyright of CT Theory & Applications is the property of Editorial Department of CT Theory & Applications and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective To identify the causative variants in 5 Chinese families with tuberous sclerosis complex (TSC) to provide genetic counseling and prenatal diagnosis. Methods Genetic counseling and clinical diagnosis were performed in 8 patients from five unrelated TSC families by teleconsultation. With informed consent obtained from the participants, 3 to 5 mL peripheral blood samples were collected from the probands and their family members for the extraction of genomic DNA. Candidate pathogenic variants were screened by panel sequencing (PS). The candidate pathogenic variants found in TSC1 and TSC2 by PS were validated by PCR-Sanger sequencing and bioinformatics analysis. Results All the pathogenic mutations were identified in the probands and their available family members. Causative variants in TSC1 or TSC2 were detected in all patients, including three reported variants and two novel variants. The two novel variants, TSC2:c.245G＞ A and TSC2: c.235delG, which were predicted to cause the nonsense variant p.(Trp82*) and the frameshift variant p.(Val79Lysfs27*) respectively was believed to introduce premature stop codons. The analysis of family co-segregation and bioinformatics were identified as very positive factors for pathogenicity. Conclusions This result provides more evidences for the genetic counseling and prenatal diagnosis in these families and expand the spectrum of TSC2 pathogenic variants.

Tuberous sclerosis complex (TSC) is an autosomal dominant hereditary disease that affects multiple organs and systems throughout the body. TSC-associated kidney disease is the leading cause of death in adult TSC patients. This article retrospectively analyzed the characteristics of one TSC-related renal giant angiomyolipoma(RAML)treated with surgery. The patient, 25 years old, was diagnosed with tuberous sclerosis complex in 2000 due to multiple maculopapular rashes on both cheeks. At a regular follow-up in July 2019, imaging examinations revealed a tumor in the left lower quadrant with a maximum cross-sectional area of 16 cm×7 cm. Genetic testing showed a loss of heterozygosity in the EX18_ 41 of TSC2. After the diagnosis was confirmed, open left partial nephrectomy was performed, during which multiple tumors were found on the kidney surface and the largest one was located on the ventral side with a diameter of approximately 20 cm. After the renal artery was occluded, kidney tumors were completely enucleate. Postoperative pathological confirmed the diagnosis of angiomyolipoma. This case provides a reference for the treatment of TSC-related renal giant hamartoma.

ObjectiveTuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disease involving multiple organ system. Renal angiomyolipoma (RAML) is a leading cause of death for adult TSC patients. Our study aims at investigating the clinical manifestations of TSC-RAML to enable clinicians to have a better understanding of the disease in Chinese patients.MethodsWe reviewed retrospectively the data collected from patients with TSC-RAML in Peking Union Medical College Hospital from January 2014 to January 2023. We also collected information about the age, gender, imageological examination, RAML stage, and comorbidities.ResultsA total of 186 TSC-RAML patients were registered, 65 of whom were males and 121 were females(male-to-female ratio 1∶1.86). The median age of all patients was 31 years old. Totally, 117 cases (62.9%)of RAML were rated stage 6. Twenty-two cases (11.8%) had a history of tumor rupture and bleeding. Research shows statistical differences between high and low grade on RAML rupture bleeding(P=0.0475). Angiofibromas/fibrous cephalic plaque (155/186, 83.3%), subependymal nodules(103/146, 70.5%), lymphangioleiomyomatosis (102/157, 65.0%), hypomelanotic macules (114/186, 61.3%), and shagreen patch (83/186, 44.6%)were the most common clinical manifestations. All patients with lymphangioleiomyomatosis(LAM) were female(P < 0.0001).ConclusionsFemale patients predominated TSC-RAML patients. Most RAML were in stage 6. About 11.8% cases had a history of tumor rupture and hemorrhage. The higher grade meant the higher proportion of tumor rupture and hemorrhage. Dermatological and nervous lesions were the most common comorbidities. All patients with LAM in this study were female.

Tuberous sclerosis complex(TSC) is a rare autosomal dominant genetic disorder caused by mutations in the TSC1 or TSC2 genes. The disease can cause multiple organ lesions. The most common renal lesions are renal angiomyolipoma(RAML). In recent years, China has made progresss in the understanding of TSC-RAML, so that the standardization of the diagnosis and management of TSC-RAML have improved. Efforts have been taken in the studies of the pathogenesis and treatment of TSC-RAML. This article reviews the diagnosis, therapy, and research development of TSC-RAML in China.

Tuberous sclerosis complex(TSC)is a rare genetic disease that can lead to benign dysplasia in multiple organs such as the skin, brain, eyes, oral cavity, heart, lungs, kidneys, liver, and bones. Its main symptoms include epilepsy, intellectual disabilities, skin depigmentation, and facial angiofibromas, whilst incidence is approximately 1 in 10 000 to 1 in 6000 newborns. This case presents a middle-aged woman who initially manifested with epilepsy and nodular depigmentation. Later, she developed a lower abdominal mass, elevated creatinine, and severe anemia. Based on clinical features and whole exome sequencing, the primary diagnosis was confirmed as TSC. Laboratory and imaging examinations revealed that the lower abdominal mass originated from the uterus. CT-guided biopsy pathology and surgical pathology suggested a combination of leiomyoma and abscess. With the involvement of multiple organs and various complications beyond the main diagnosis, the diagnostic and therapeutic process for this patient highlights the importance of rigorous clinical thinking and multidisciplinary collaboration in the diagnosis and treatment of rare and challenging diseases.

Copyright of Basic & Clinical Medicine is the property of Editorial Office of Basic & Clinical Medicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Rapamycin is a mammalian target of rapamycin(mTOR) receptor inhibitor. Advances in the understanding of the mTOR signaling pathway and its downstream effects on tumorigenesis and vascular proliferation have broadened the clinical applications of mTOR receptor inhibitors in treating many challenging diseases. Rapamycin is used orally for the treatment of kidney transplantation, lymphatic leiomyomatosis of lung, tuberous sclerosis complex(TSC), and etc. But systemic therapy using the rapamycin has significant side effects. To mitigate the side effects of systemic rapamycin for dermatologic applications, clinicians have used topical therapy. In recent years, research publications on the topical rapamycin in the treatment of a variety of diseases have increased, as on such diseases of facial angiofibroma of tuberous sclerosis complex, lymphatic malformation, Kaposi hemangioendothelioma, tufted angiomas, and etc. Topical rapamycin can be used as an effective long-term therapy while avoiding systemic side effects, providing a new treatment method for dermatologists. This paper discusses the progress in the treatment of topical rapamycin preparations.

Objective To analyze the clinical,CT and MRI characteristics of tuberous sclerosis complex (TSC) to raise awareness of multiple organ damage in this disease. Methods The clinical, CT and MRI characteristics of 12 cases of clinically confirmed TSC in Nanjing Jiangbei Hospital from September 2015 to June 2020 were retrospectively analyzed. Results TSC involved multiple organs and showed different changes in clinical imaging (the count of cases may overlap). In central nervous system, there were 9 cases of typical subependymal nodule, including 7 calcified nodules and 2 non-calcified nodules; 5 cases of cortical and subcortical nodule, 3 cases of white matter signal change, 1 case of subependymal giant cell astrocytoma. In abdomen,there were 8 cases of angiomyolipoma of different sizes in both kidneys (of which 2 cases were accompanied by intratumoral hemorrhage) and 1 case of multiple hepatic angiomyolipoma. In chest, there were 2 cases of pulmonary lymphangioleiomyomatosis and 1 case of cardiac rhabdomyoma. In bone, there was 1 case of multiple nodular and patchy osteosclerosis. Conclusion The analysis of clinical imaging features of TSC multi-system tumor is helpful for the diagnosis of TSC.

Objective To explore the effect of sodium hydroxide(NaOH) and rapamycin(Rapa) alone or their combination in treating Tsc2-null(Tsc2-/-) mouse embryonic fibroblasts. Methods The wild type and Tsc2-/- cells were treated with NaOH and/or Rapa and divided into 4 groups: control, NaOH group, Rapa group, and combination (Combo) group. Cell proliferation was measured by MTT assay and colony formation. Flow cytometry was used to detect the potential influence on cell cycle. The protein expression of S6, p-S6, p-4EBP1 was detected by Western blot. Results Compared to control group, Tsc2-/- cells in NaOH and Rapa groups both showed a reduced proliferation ability and colony counting (P＜0.05); additionally, only in Rapa group, the percentage of Tsc2-/- cells in G1 phase increased and the protein level of p-S6 and p-4EBP1 all decreased (P＜0.05). Compared with NaOH and Rapa groups, Tsc2-/- cells in Combo group had a further decreased in proliferation ability and colony number and an increased G1 phase percentage (P＜0.05). But the level of p-S6 and p-4EBP1 of Tsc2-/- cells in Combo group was significantly lower than those in NaOH group (P＜0.05). Conclusions NaoH(15 μmol/L) enhances the suppressing poliferation efficacy of Rapa in Tsc2-/- cells.

To explore the clinical characteristics and genotype characteristics of children with tuberous sclerosis com-plex (TSC) with epilepsy, in order to understand the clinical manifestations of children with TSC with epilepsy, and the correlation between phenotype and genotype, so as to provide a more effective scheme for clinical diagnosis and treatment. The clinical manifestations of 10 children with TSC with epilepsy who were treated in the Department of Neurology of Anhui children's Hospital from December 2019 to January 2021 were analyzed retrospectively. The gene detection was performed on children with TSC with epilepsy and their parents by chip capture high-throughput sequencing and Sanger sequencing validation, and the characteristics of clinical and genetic variation were analyzed. Among the 10 cases, 4 were male, and 6 were female, 3 were first convulsive, and 7 were focal, and 70.00% initial age were younger than 1 year old. Clinical manifestations: 90.00% skin lesions, 80.00% cardiac rhabdomyoma,20.00% fundus abnormalities, no kidney, liver, lung lesions. Video electroencephalogram showed 60.00% epileptic wave in frontotemporal region, 100.00% with neuroimaging cortical/subcortical abnormalities, 90.00% bilateral ependymal/subependymal abnormalities, and10.00% subependymal giant cell astrocytoma. Gene testing was completed in all the children in the study, including 3 cases of TSC1gene mutation, 7 cases of TSC2 mutation, including missense, frameshifting and splicing site mutation. Family variation was detected in2 cases, and no family variation was detected in 7 cases. There is no significant difference in the incidence of TSC with epilepsy between male and female, and sporadic cases are more common. The initial age is less than 1 year, and the first onset is of ten focal. Epileptic wave in video electroencephalogram is dominant in frontotemporal region, and cortical/subcortical and bilateral ependymal/subependymal abnormalities are found in head imaging. TSC2 mutation is more common than TSC1 mutation, with severe clinical manifestations, high incidence of convulsion, younger age of onset and poor control. Early genetic testing is particularly important for children at younger age of onset and with poor efficacy. [ABSTRACT FROM AUTHOR]

Objective Preoperative and postoperative scalp electroencephalogram(EEG) analysis was performed and analyzed on 16 patients who underwent epileptic foci resection. To determine if focal ictal epileptiform discharge can predict surgery effect. Methods All patients were monitored by video electroencephalogram(EEG) to determine the discharge location and onset area. 11 patients underwent direct tuber resection and 5 patients underwent thermocoagulation or second resection followed by SEEG implantation. Results 12 of the 16 patients was Engel Ⅰ after surgery. 3 of the 12 patients were focal seizure, and 9 were comprehensive or hemispheric seizure. Among the 16 patients, 4 were Engel Ⅱ after surgery, among which 2 were non-focal seizure and 2 patients were focal seizure. Scalp EEG with focal onset and non-focal onset had no statistical significance in predicting prognosis of surgery. Conclusion Scalp EEG in patients with tuberous sclerosis complex was mainly analyzed before and after surgery. It is instructive for the operation evaluation of patients with tuberous sclerosis complex. [ABSTRACT FROM AUTHOR]

Objective: To retrospect the clinical features and the current situation of the diagnosis of patients with TSC in China to promote the identification, standardized diagnosis and management of patients with TSC. Methods: The literatures related to 3171 Chinese TSC patients selected from among 269 articles for further analysis with reference to the existence of skin lesions, neurological manifestations, renal, cardiac and pulmonary lesions were comprehensively searched in VIP, Wanfang, CNKI, CBM, and PubMed database from 2011 to 2014. Results: Compared to the main indications of the diagnostic criteria in 2012 TSC Diagnosis Guideline, a total of 247 papers described skin lesions on 2607 cases of TSC patients. The 2395 TSC patients from 212 papers were found to bear neurological lesion(s) based upon imaging data. A total of 84 TSC patients were reported to develop multiple retinal hamartoma as revealed by eye fundus examination on 348 patients studied in 55 papers. With color Doppler ultrasonography, 162 cases inflicted with rhabdomyoma of the heart were identified from out of 282 patients reported in 32 papers. X-ray chest film screening was conducted on282 patients in 45 papers and another 20 papers used chest CT scan to examine 36 patients, revealing up to a total of 50 cases of TSC patients with rhabdomyomatosis. Renal ultrasonongraphy was performed on 696 patients presented in 98 papers, while 221 cases in 51 papers had received renal CT scanning, and 2 separate papers described a total of 2 cases with renal MRI procedures, thus leading to the recognition of 416 cases of TSC to have angioleiomyoma in their kidneys. Through hepatic ultrasonography carried out for 586 cases with TSC in 58 papers, abdominal CT scan done on 104 cases in 30 papers and abdominal MRI on 3 cases in 2 papers, a total of 141 cases of TSC were found to have hepatic angioleiomyoma. In the reporting of secondary indications in diagnostic criteria, most of the multiple renal cystic disease were reported, but less oral fibroma and confetti skin lesion were reported. In the study about other clinical manifestations, the most reported were epilepsy, the literature about intelligence assessment still lacks objective intelligence evaluation standard. Genetic gene testing has gradually become the focus in recent years. Conclusion: Over the past 13 years, clinicians in China have done tremendously in diagnosing and treating the disease. However, due to the presence of misdiagnosis or omitted diagnosis,widespread adoption of TSC Diagnosis Guide would be advantageous. [ABSTRACT FROM AUTHOR]

Copyright of China Tropical Medicine is the property of China Tropical Medicine Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective To study the clinicopathology, immunohistochemical characteristic and the differential diagnosis of subependymal giant cell astrocytomas (SEGAs). Methods Two cases of SEGAs were studied by clinicopathological study and immunohistochemistry. Results Two cases of SEGAs occurred during the first two decades of life, arising in the wall of the lateral ventricles and were composed of gemistocytes and sweeping bundles of spindle cells with calcification. Immunohistochemistry showed GFAP, S-100, vimentin, Map-2, Nestin, SOX-2, Caspase-3, Caspase-9 and Bax positive; Neun, CD133, CD34 and Ki-67 negative. Conclusions SEGAs occur commonly in tuberous sclerosis complex, may arise from multipotent neural stem cells, have activation of apoptotic mechanisms and should be differentiated with gemistocytic diffuse astrocytoma, ependymoma, choroid plexus papilloma and subependymoma. [ABSTRACT FROM AUTHOR]

This paper reported a sporadic case of a 29-year-old Han female diagnosed with tuberous sclerosis complex (TSC) by next generation sequencing (NGS), one of genetic analysis techniques. She was admitted because of recurrent intractable seizure for 26 years, dizziness and headache for 3 months. Physical examination revealed angiofibromas over her face, shagreen patches in her lower back area, and hypomelanotic macules around her limbs and body. Cranial MRI manifested lesions on lateral ventricles, cerebellar vermis and left temporal lobe with abnormal signal changes on both sides of extensive cerebral cortex. A pathogenic and heterozygous missense mutation, C.T1967C, in exon 16 of her TSC1 gene was found via genetic tests, which has not yet been reported before. [ABSTRACT FROM AUTHOR]

We reported a case of tuberous sclerosis complex with facial angiofibroma as the initial presentation and conducted a multidisciplinary discussion. The patient, a young female, was admitted to the Department of Dermatology for cosmetic purpose. After the examination, she was found to have multiple system involvement, including a large renal angiomyolipoma pressing on the liver. She never had any subjective symptom. After consultation by the multidisciplinary team of tuberous sclerosis complex, the patient was treated with everolimus orally and followed up regularly. It is suggested that dermatologists should pay attention to the systemic involvement of patients with tuberous sclerosis complex. Early intervention can prolong the life of patients and improve their life quality. Multidisciplinary collaboration for lifelong disease management is the key to enhance the diagnosis and treatment for tuberous sclerosis complex and enhance the prognosis of patients.

Objective: Tuberous sclerosis complex (TSC) is a multi-system disease with TSC1 and TSC2 genes as the pathogenic genes. The purpose of our study was to analyze the gene mutation in patients with TSC with epilepsy as the main clinical manifestation. The relationship between genotype and phenotype, scalp EEG in patients was analyzed. Methods: The peripheral blood was extracted from 43 patients and their families. TSC gene was detected by second-generation sequencing. Long-term video EEG monitoring and MRI examination were performed to determine the onset area, seizure type and location of nodules. Results: 39 patients had TSC gene mutation, 4 patients did not detect the gene mutation.11 had TSC1 mutations and 28 had TSC2 mutations. 22 mutations were de novo. Patients with TSC2 mutations had earlier seizure and more nodules than patients with TSC1 mutations, but no significant difference in intelligence and spasm were observed. 28 patients had focal origin of scalp EEG, of which 85.7% of TSC2 mutations patients had focal origin. Conclusions: Patients of TSC2 mutations always has an early onset age. Although MRI shows multiple nodules, the onset of EEG is mainly focal origin.