tuberous sclerosis

INTRODUCTION: Chordoma is a rare slow-growing tumor that occurs along the length of the spinal axis and arises from primitive notochordal remnants (Stepanek et al., Am J Med Genet 75:335-336, 1998). Most chordomas are sporadic, but a small percentage of cases are due to hereditary cancer syndromes (HCS) such as tuberous sclerosis 1 and 2 (TSC1/2), or constitutional variants in the gene encoding brachyury T (TBXT) (Pillay et al., Nat Genet 44:1185-1187, 2012; Yang et al., Nat Genet 41:1176-1178, 2009)...

Autism (or autism spectrum disorder) was initially defined as a psychiatric disorder, with the likely cause maternal behavior (the very destructive "refrigerator mother" theory). It took several decades for research into brain mechanisms to become established. Both neuropathological and imaging studies found differences in the cerebellum in autism spectrum disorder, the most widely documented being a decreased density of Purkinje cells in the cerebellar cortex. The popular interpretation of these results is that cerebellar neuropathology is a critical cause of autism spectrum disorder...

Tuberous sclerosis (TS) is a rare multisystem autosomal dominant genetic disorder with characteristic pathognomonic genetic mutations involving the TSC (tuberous sclerosis complex) group of genes. Ocular signs are fairly common and include an achromic patch and retinal astrocytic hamartomas, which usually have a maximum size of between 0.5 and 5 mm. The incidence of tuberous sclerosis is estimated to be 1 in 5000-10,000 individuals, with both familial and sporadic cases reported. The diagnostic criteria for tuberous sclerosis include the presence of major and/or minor clinical features as well as genetic mutations...

BACKGROUND: MiR-136-5p plays a vital function in regulating developmental processes as well as in the pathophysiology of diseases, with a notable record in tumor suppression. METHODS: This article summarizes the latest findings on the physiological and pathophysiological processes of miR-136-5p in diseases. We searched for relevant studies and selected research articles from the last five years on PubMed with miR-136-5p as the keyword. RESULTS: MiR-136-5p represents a class of microRNAs (miRNAs) that are involved in various human maladies, encompassing cancers, cardio-cerebrovascular disease, diabetes, inflammatory disease, tuberous sclerosis, idiopathic pulmonary fibrosis, and polycystic ovary syndrome...

No abstract text is available yet for this article.

We recently demonstrated that acute oral ketone monoester intake induces a stimulation of postprandial myofibrillar protein synthesis rates comparable to that elicited following the ingestion of 10 g whey protein or their co-ingestion. The present investigation aimed to determine the acute effects of ingesting a ketone monoester, whey protein, or their co-ingestion on mTOR-related protein-protein co-localization and intracellular trafficking in human skeletal muscle. In a randomized, double-blind, parallel group design, 36 healthy recreationally active young males (age: 24...

Tuberous sclerosis (TSC) is a rare autosomal dominant disorder that can affect multiple organ systems, including the brain, heart, lungs, and skin. Cutaneous manifestations are common, including ungual fibromas, however, these may be mistaken for other pathologies. Here, we present the case of a 14-year-old with TSC complaining of traumatic left little finger pain. Radiographic evaluation revealed cortical scalloping of the nailbed, concerning for a non-displaced fracture. Given the history of TSC, however, this defect may have also represented a periungual fibroma...

INTRODUCTION: Pediatric cystic kidney disease (CyKD) includes conditions characterized by renal cysts. Despite extensive research in this field, there are no reliable genetics or other biomarkers to estimate the phenotypic consequences. Therefore, CyKD in children heavily relies on clinical and diagnostic testing to predict the long-term outcomes. AIM: A retrospective study aimed to provide a concise overview of this condition and analyze real-life data from a single-center pediatric CyKD cohort followed during a 12-year period...

BACKGROUND: The thyroid gland is susceptible to abnormal epithelial cell growth, often resulting in thyroid dysfunction. The serine-threonine protein kinase mechanistic target of rapamycin (mTOR) regulates cellular metabolism, proliferation, and growth through two different protein complexes, mTORC1 and mTORC2. The PI3K-Akt-mTORC1 pathway's overactivity is well associated with heightened aggressiveness in thyroid cancer, but recent studies indicate the involvement of mTORC2 as well. METHODS: To elucidate mTORC1's role in thyrocytes, we developed a novel mouse model with mTORC1 gain of function in thyrocytes by deleting Tuberous Sclerosis Complex 2 (TSC2), an intracellular inhibitor of mTORC1...

BACKGROUND: Tuberous sclerosis complex (TSC) is a multisystem neurocutaneous syndrome with variable phenotypes. Recent updates of TSC diagnostic criteria reaffirmed the defined genetic diagnostic criterion as the finding of a pathogenic DNA alteration in either TSC1 or TSC2 genes. It also slightly modified definite clinical diagnostic criteria. TSC-associated skin lesions in infancy are important clinical signs to select individuals with possible TSC for a closer clinical follow-up and genetic testing...

BACKGROUND AND OBJECTIVE: Lymphangioleiomyomatosis (LAM) is a rare neoplastic disease associated with the functional tumour suppressor genes TSC1 and TSC2 and causes structural destruction in the lungs, which could potentially increase the risk of lung cancer. However, this relationship remains unclear because of the rarity of the disease. METHODS: We investigated the relative risk of developing lung cancer among patients diagnosed with LAM between 2001 and 2022 at a single high-volume centre in Japan, using data from the Japanese Cancer Registry as the reference population...

No abstract text is available yet for this article.

The plasticity and diversity of cell types with specialized functions likely defines the capacity of multicellular organisms to adapt to physiologic stressors. The kidney collecting ducts contribute to water, electrolyte, and pH homeostasis and are composed of mature intermingled epithelial cell types that are susceptible to transdifferentiate. The conversion of kidney collecting duct principal cells to intercalated cells is actively inhibited by Notch signaling to ensure urine concentrating capability. Here we identify Hes1, a target of Notch signaling, allows for maintenance of functionally distinct epithelial cell types within the same microenvironment by regulating mechanistic target of rapamycin complex 1 (mTORC1) activity...

BACKGROUND: Overactivity is prevalent in several rare genetic neurodevelopmental syndromes, including Smith-Magenis syndrome, Angelman syndrome, and tuberous sclerosis complex, although has been predominantly assessed using questionnaire techniques. Threats to the precision and validity of questionnaire data may undermine existing insights into this behaviour. Previous research indicates objective measures, namely actigraphy, can effectively differentiate non-overactive children from those with attention-deficit hyperactivity disorder...

We present the case of a 6-year-old girl who initially presented with acute pelvic pain, ultimately diagnosed with imperforate hymen leading to hematocolpos. Further investigation revealed additional clinical features including academic struggles, mood swings, and cutaneous findings, prompting consideration of a neurocutaneous syndrome. Magnetic Resonance Imaging (MRI) revealed features consistent with tuberous sclerosis complex (TSC), including radial migration lines in the subcortical white matter and an incidental arachnoid cyst...

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...

Lymphangioleiomyomatosis (LAM) is a rare, progressive cystic lung disease affecting almost exclusively female-sexed individuals. The cysts represent regions of lung destruction caused by smooth muscle tumors containing mutations in one of the two tuberous sclerosis (TSC) genes. mTORC1 inhibition slows but does not stop LAM advancement. Furthermore, monitoring disease progression is hindered by insufficient biomarkers. Therefore, new treatment options and biomarkers are needed. LAM cells express melanocytic markers, including glycoprotein non-metastatic melanoma protein B (GPNMB)...

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...