Tuberous Sclerosis Complex

The Index for Facial Angiofibromas (IFA), a novel scoring system for angiofibromas, has been validated in patients with tuberous sclerosis complex (TSC). The objective of this analysis was to further validate the IFA using data from a clinical trial of topical sirolimus in patients with TSC. This was an analysis of photographs from a Phase III trial conducted in Japan (NCT02635789). Patients (n = 62) were randomized 1:1 to receive sirolimus or placebo gel for 12 weeks. Changes in angiofibromas were independently assessed using the primary composite endpoint, the Facial Angiofibroma Severity Index (FASI), and the IFA...

80% of renal carcinomas (RC) are diagnosed incidentally by imaging. 2-4% of "sporadic" multifocality and 5-8% of hereditary syndromes are accepted, probably with underestimation. Multifocality, young age, familiar history, syndromic data, and certain histologies lead to suspicion of hereditary syndrome. Each tumor must be studied individually, with a multidisciplinary evaluation of the patient. Nephron-sparing therapeutic strategies and a radioprotective diagnostic approach are recommended. Relevant data for the radiologist in major RC hereditary syndromes are presented: von-Hippel-Lindau, Chromosome-3 translocation, BRCA-associated protein-1 mutation, RC associated with succinate dehydrogenase deficiency, PTEN, hereditary papillary RC, Papillary thyroid cancer- Papillary RC, Hereditary leiomyomatosis and RC, Birt-Hogg-Dubé, Tuberous sclerosis complex, Lynch, Xp11...

Hypercholesterolaemia is a systemic metabolic disease, but the role of organs other than liver in cholesterol metabolism is unappreciated. The phenotypic characterization of the Tsc1Dmp1 mice reveal that genetic depletion of tuberous sclerosis complex 1 (TSC1) in osteocytes/osteoblasts (Dmp1-Cre) triggers progressive increase in serum cholesterol level. The resulting cholesterol metabolic dysregulation is shown to be associated with upregulation and elevation of serum amyloid A3 (SAA3), a lipid metabolism related factor, in the bone and serum respectively...

BACKGROUND: The TAND (Tuberous Sclerosis Complex [TSC]-Associated Neuropsychiatric Disorders) Checklist was developed as a clinical screener for neurodevelopmental disorders in TSC. Most studies have described patterns in older children and adults. This study sought to better understand behavioral concerns as measured by the TAND Checklist in young children with TSC. METHODS: We examined patterns of caregiver responses to the TAND Checklist in 90 toddlers with TSC (12 to 23 months n = 60; 24 to 36 months n = 30) through data collected during baseline visits across two TSC early intervention studies...

BACKGROUND: Patients with platinum-resistant recurrent high grade serous ovarian carcinoma have poor outcomes and limited treatment options. CASE PRESENTATION: We present a case of a 48-year-old woman with platinum-resistant high grade serous ovarian carcinoma harboring the pathogenic TSC2 R611Q variant with concomitant single copy loss of TSC2 (suggesting biallelic TSC2 inactivation) identified in targeted tumor sequencing. The patient was treated with the mTOR inhibitor everolimus, with an excellent response by imaging and a marked decrease in CA125; she remained on everolimus for 19 months until she developed progressive disease...

Lymphangioleiomyomatosis (LAM) is an abnormal proliferation of smooth muscle-like cells and may occur sporadically or in association with tuberous sclerosis complex. Patients are typically female, nonsmoking and may have cystic lung disease with pneumothorax. Diagnosis can be made by compatible imaging findings with a history of tuberous sclerosis complex, or in conjunction with vascular endothelial growth factor-D 800 pg/ml or greater, a highly specific finding. Sirolimus is first line treatment for LAM.

Lymphangioleiomyomatosis (LAM) represents a rare, insidiously progressive disease of the pulmonary system, marked by cystic degradation of lung tissues leading to respiratory compromise. Pulmonary LAM has been identified as being associated with tuberous sclerosis complex (TSC) in its pulmonary manifestation (TSC-LAM), a multisystem genetic disorder resulting from mutations in either the TSC1 or TSC2 genes. Herein, we describe an early 20s female admitted to the hospital with dyspnea, chest pain, hypopigmented macules, and facial fibroadenomas...

Tuberous Sclerosis Complex (TSC) is a rare genetic disorder that primarily affects the central nervous system and various body organs. This case series describes the case history of 2 siblings from the same parents who were diagnosed with TSC. Case 1 is a 13-year-old girl with bilateral renal AML (angiomyolipoma), multiple fat nodules in the liver, and subependymal nodules with tubers revealed in the brain magnetic resonance imaging (MRI). Case 2 is her brother, a 6-year-old boy, who presented with manifestations of subependymal giant cell astrocytoma (SEGA) and renal AML...

A recent study described a rare subtype of tuberous sclerosis complex (TSC)-mutated renal cell carcinoma primarily characterized by Xanthomatous giant cell morphology. Only 2 cases in young individuals have been reported so far, making the correct diagnosis challenging from a pathological perspective. It remains unknown whether this tumor represents an independent subtype or belongs to other TSC-mutated tumors. We conducted a clinicopathologic evaluation and immunohistochemical profiling of 5 cases of Xanthomatous Giant Cell Renal Cell Carcinoma (XGC RCC) with confirmed TSC2 mutations through targeted DNA sequencing...

Subependymal giant cell astrocytoma (SEGA) represents a benign brain tumor occurring in 5-20% of individuals diagnosed with tuberous sclerosis complex (TSC), serving as a major diagnostic criterion. The presence of SEGA in a patient often prompts consideration of TSC as a probable diagnosis, given its unique association with this disorder. Typically, only one additional major criterion or two minor criteria are necessary to fulfill the diagnostic criteria for TSC. However, in rare instances, SEGA may manifest in patients without clinical features of TSC, termed solitary SEGA...

INTRODUCTION: Bournevile disease is a rare global condition that presents a diagnostic challenge due to its diverse multisystemic involvement. CASE PRESENTATION: This report presents the case of a 14-year-old male with a medical history of congenital single kidney, heart rate abnormalities, Bournevile disease with cognitive deficits, brain lesions, and dermatological features. The patient presented with sudden onset renal angiolipomatosis, and the diagnosis was based on specific computed tomography (CT) findings...

Tuberous Sclerosis Complex (TSC) is a severe developmental disorder with various clinical effects, primarily caused by TSC2 gene mutations, often involving loss of function(Henske,et al., 2016).To explore role of TSC2 in human heart development, we successfully developed a TSC2 knockout (TSC2-/-) human embryonic stem cells (hESCs) line using CRISPR/Cas9 gene editing. This TSC2-/- hESC line maintained a normal karyotype, expressed pluripotency markers strongly, and could differentiate into all three germ layers in vivo...

The manifestations of tuberous sclerosis complex (TSC) in humans include epilepsy, autism spectrum disorders (ASD) and intellectual disability. Previous studies suggested the linkage of TSC to altered cerebral blood flow and metabolic dysfunction. We previously reported a significant elevation in cerebral blood flow in an animal model of TSC and autism of young Eker rats. Inhibition of the mammalian target of rapamycin (mTOR) by rapamycin could restore normal oxygen consumption and cerebral blood flow. In this study, we investigated whether inhibiting a component of the mTOR signaling pathway, p70 ribosomal S6 kinase (S6K1), would yield comparable effects...

The present work reports the autopsy findings of a unique case characterized by fatal retroperitoneal hemorrhage following the traumatic rupture of bilateral renal angiomyolipomas. Renal angiomyolipomas are generally benign tumors with an unpredictable clinical course, ranging from asymptomatic to sudden rupture and hemorrhagic shock. They may be associated with genetic disorders such as tuberous sclerosis complex. The case under investigation is unprecedented in the medical literature due to its bilateral nature and fatal outcome...

INTRODUCTION: Tuberous sclerosis complex (TSC) is caused by variants in TSC1/TSC2, leading to constitutive activation of the mammalian target of rapamycin (mTOR) complex 1. Therapy with everolimus has been approved for TSC, but variations in success are frequent. Recently, caudal late interneuron progenitor (CLIP) cells were identified as a common origin of the TSC brain pathologies such as subependymal giant cell astrocytomas (SEGA) and cortical tubers (CT). Further, targeting the epidermal growth factor receptor (EGFR) with afatinib, which is expressed in CLIP cells, reduces cell growth in cerebral TSC organoids...

INTRODUCTION: Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), and tuberous sclerosis complex (TSC)-associated epilepsy are rare conditions associated with severe childhood-onset epilepsy. Caregivers play a critical role in the patients' care and may experience significant psychosocial and socioeconomic burden. This cross-sectional study determined the burden of caring for patients with these rare epilepsy conditions in Japan. METHODS: A quantitative online survey was used to assess patients' and caregivers' characteristics and the caregivers' emotional state, among others...

Insulinoma and glucagonoma are two rare functioning neoplasms of the neuroendocrine cells of the pancreas, respectively characterized by an uncontrolled over-secretion of insulin or glucagon, responsible for the development of the hypoglycemic syndrome and the glucagonoma syndrome. They prevalently arise as sporadic tumors; only about 10% of cases develop in the context of rare inherited tumor syndromes, such as Multiple Endocrine Neoplasia Type 1 (MEN1), Neurofibromatosis type 1 (NF1), and Tuberous Sclerosis Complex (TSC), being the result of an autosomal dominant germline heterozygous loss-of-function mutation in a tumor suppressor gene...

CONTEXT.—: Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors of uncertain histogenesis expressing smooth muscle and melanocytic markers. The clinicopathologic spectrum in young patients is not well documented. OBJECTIVE.—: To describe a multi-institutional series of PEComas in children, adolescents, and young adults. DESIGN.—: PEComas, not otherwise specified (NOS); angiomyolipomas (AMLs); lymphangioleiomyomatosis; and clear cell sugar tumors were retrospectively identified from 6 institutions and authors' files...

Tuberous sclerosis complex (TSC) is a neurocutaneous disease that manifests across multiple body systems. While there are substantial guidelines and protocols for managing the physical presentation of the disease, managing the psychosocial factors and the adverse effects as a social determinant of health is complex and unclear. This study discusses a patient with TSC who was hospitalized for pneumonia and how both her psychiatric and somatic symptoms were managed. Here we present the case of a 38-year-old Caucasian female with shortness of breath and generalized weakness...

The mechanistic target of rapamycin (mTOR) pathway serves as a master regulator of cell growth, proliferation, and survival. Upregulation of the mTOR pathway has been shown to cause malformations of cortical development, medically refractory epilepsies, and neurodevelopmental disorders, collectively described as mTORopathies. Tuberous sclerosis complex (TSC) serves as the prototypical mTORopathy. Characterized by the development of benign tumors in multiple organs, pathogenic variants in TSC1 or TSC2 disrupt the TSC protein complex, a negative regulator of the mTOR pathway...