Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Tuberous sclerosis complex”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

14 recordsLinked to original sources
PubMed1979

Renal hamartoma (angiomyolipoma) and the tuberous sclerosis complex.

Renal hamartoma is found in 40 to 80 percent of patients with tuberous sclerosis. Microscopic demonstration of fat in the tissues of the mass is felt to be the most reliable diagnostic criterion of hamartoma.Characteristically, the angiographic appearance demonstrates a large, dilated feeding vessel passing through the mass with multiple, multisacculated aneurysmal dilatations appearing like bunches of grapes. There is a delicate neovascularity without A-V shunting and an onion-peel or whorl-like appearance in the venous phase.This case is presented to point out the close association of renal hamartoma and tuberous sclerosis and the need to search for renal hamartoma when the diagnosis of tuberous sclerosis is made.

Adenoma↗
PubMed2025

TSC angiofibroma and ungual fibroma have different mutation signatures, with recurrent mutations in KMT2C.

PURPOSE: Tuberous sclerosis complex (TSC) is an autosomal dominant tumor suppressor syndrome characterized by tumors affecting multiple tissues, including skin, due to inactivating TSC1/TSC2 variants. Genome-wide profiling of somatic mutations in a unique collection of angiofibroma (FAF) and ungual fibroma (UF) TSC skin tumors was performed. METHODS: Genome sequencing was performed on 9 samples, comprising 4 FAF and 5 UF, along with 6 matched normal samples from 6 individuals with TSC. RESULTS: TSC-FAF and TSC-UF skin tumors have different mutation signatures, with a predominance of UV-related single-nucleotide variant (SNV; SBS7a and SBS7b) and dinucleotide variant (DNV; DBS1) signatures in FAF, and aging-related SNV (SBS1 and SBS5) signatures in UF. We also identified a novel DNV signature for TSC-UF, with frequent TG>CA and TT>GG substitutions. Furthermore, 3 inactivating somatic mutations in KMT2C were observed in 2 of 4 TSC-FAF and 5 mutations in other cancer genes. CONCLUSION: The distinct SNV mutation signatures seen in TSC-FAF and UF indicate that they develop through distinct pathogenic mechanisms, UV-induced mutagenesis in FAF, and aging-related mutagenesis in UF. The mechanism of the novel DNV signature in UFs merits further investigation. Our observation on the occurrence of KMT2C mutations suggests that KMT2C inactivation contributes to the pathogenesis of TSC-FAF.

Humans↗
PubMed2026

Pancreatic neuroendocrine tumors in patients with tuberous sclerosis: a multicenter study and systematic review.

INTRODUCTION: Pancreatic neuroendocrine tumors (pNETs) are a recognized feature of tuberous sclerosis complex (TSC). The current evidence suggests that pNETs occurring in TSC may exhibit a different clinical course from sporadic cases, but their natural history remains poorly characterized. OBJECTIVE: This study aimed to characterize the demographics, clinical presentation, management, and long-term outcomes of TSC-associated-pNETs and to propose possible guidelines for surveillance and management. MATERIALS AND METHODS: We conducted a multicenter retrospective review of TSC-pNET patients from 6 UK TSC specialist clinics and from 3 NET referral centers, from 2008 to 2024. Data on demographics, tumor characteristics, management, and outcomes, were collected. A systematic review of the literature from 2009 to 2026 on TSC-pNETs was also performed. RESULTS: We identified a total of 26 consecutive cases with the TSC-pNET-association in our cohort: 21 cases of pNETs from TSC specialist clinics (1.1% of the population), and 5 cases of TSC-pNETs from the NET referral centers (0.25% of the population). An additional 80 cases were identified from the published literature. We observed a wide spectrum of clinical phenotypes, with the majority being nonfunctioning pNETs (n = 24; 92%), whereas 2 patients were diagnosed with glucagonomas. Surgical intervention was the mainstay initial treatment, the indication being either functional pNETs, or large or symptomatic nonfunctioning pNETs. CONCLUSION: TSC-pNETs are rare and mostly nonfunctioning tumors with variable clinical behavior. Due to their uncertain malignant potential, we suggest that baseline pancreatic imaging should be incorporated into TSC surveillance, and we emphasize the need for heightened pNET surveillance and updated management recommendations.

TS complex↗
PubMed2026

Long-term seizure outcomes and factors associated with response to adjunctive everolimus in TSC-associated epilepsy.

BACKGROUND: Everolimus, a mechanistic target of rapamycin (mTOR) inhibitor, is increasingly used in tuberous sclerosis complex (TSC)-associated epilepsy; however, long-term real-world outcomes and factors associated with favorable response remain unclear. This study aimed to evaluate the long-term seizure outcomes of adjunctive everolimus and explore clinical factors associated with treatment response. METHODS: We retrospectively recruited 21 patients with active TSC-associated epilepsy receiving adjunctive everolimus and assessed seizure outcomes during follow-up. Clinical characteristics were compared between responders and non-responders at 1 year after treatment initiation. RESULTS: Over a median treatment duration of 72 months, responder rates ranged from 53.8% to 64.7%, and seizure-free rates ranged from 33.3% to 41.2%. Responders had fewer involved organ systems at baseline (median 3 vs. 4, p = 0.020) and lower anti-seizure medication burden (median 2 vs. 4, p = 0.045). Younger age at treatment initiation showed a trend toward improved response. CONCLUSION: Adjunctive everolimus was associated with sustained long-term seizure reduction in this real-world cohort. In exploratory analyses, fewer involved organ systems and fewer baseline ASMs were associated with favorable treatment response. These findings require validation in larger prospective cohorts.

Epilepsy↗
PubMed1977

[Bilateral hamartomas of the kidneys (author's transl)].

A case of a patient with multiple bilateral hamartomas of the kidneys is reported. The diagnosis of polycystic renal disease, suggested by the urographic studies had to be corrected after renal angiography. A well established diagnosis, basing on the striking angiographical findings was only possible, when we took notice of an adenoma sebaceum and other signs of the tuberous sclerosis complex. In cases of circumscribed unifocal lesions the antiographic findings may cause difficulties in the differential diagnosis between hamartoma and malignant hypernephroma. Therefore it is important to pay attention to other stigmata of tuberous sclerosis (Bourneville-Pringle's-syndrome). The differentiation between benign hamartoma and malignant hypernephroma may be possible by angiographic criteria alone, but many of the reported typical signs are of limited value.

Adult↗
PubMed1978

Bilateral angiomyolipomas and renal cell carcinoma in polycystic kidney.

A case is presented of a twenty-eight-year-old man in whom renal failure developed at age twenty-four from polycystic kidney disease known to be present since childhood. He also had cutaneous manifestations of the tuberous sclerosis complex. Intrarenal hemorrhage led to bilateral nephrectomy. Microscopic examination disclosed typical polycystic disease and multiple angiomyolipomas in each kidney. In addition several renal cell carcinomas of oncocytic, papillary, and clear cell type were found. Review of the literature disclosed the uncommon coexistence of any two of these lesions and did not uncover any reported case of the simultaneous existence of all three.

Adenocarcinoma↗
PubMed2026

Development of a human iPSC and patient phenotyping resource for preclinical investigations of neurodevelopmental disorders.

In this manuscript, we report the development of a comprehensive resource designed to harness the transformative potential of patient-derived induced pluripotent stem cells (iPSCs) to advance the study of neurodevelopmental disorders (NDDs). Using CRISPR-Cas-mediated genome editing, the Human Neuron Core generated a repository comprising 29 isogenic iPSC pairs, two sex-matched parental control iPSC pairs, and one unmatched patient line representing six monogenic NDDs: Tuberous Sclerosis Complex, PTEN Hamartoma Tumor Syndrome, KCNQ2 Developmental and Epileptic Encephalopathy, FOXG1 Syndrome, Phelan-McDermid Syndrome, and SETBP1 Haploinsufficiency Disorder. In parallel, detailed clinical phenotyping data were collected to enable comparison of cellular phenotypes with clinical severity in future studies. This integrated collection of genetically defined iPSC lines and associated clinical data provides a powerful platform for investigating disease mechanisms and advancing iPSC-based drug discovery for NDDs.

Humans↗
PubMed1978

Symptomatic renal angiomyolipoma: report of 8 cases, 2 with spontaneous rupture.

Of the 97 patients with symptomatic renal angiomyolipoma not associated with tuberous sclerosis reported in the literature 13 have presented with a clinical picture of shock because of spontaneous rupture and massive retroperitoneal hemorrhage. Eight new patients with symptomatic renal angiomyolipomas are described, 2 of whom presented with an acute abdomen. Renal angiomyolipomas are essentially benign tumors. Several angiographic and pyelographic characteristics have been described but none appears to be unequivocally diagnostic. Because of the inability to make a precise preoperative diagnosis and the possibility of massive hemorrhage, nephrectomy is indicated in patients with such unilateral solid tumors in the absence of the tuberous sclerosis complex.

Adult↗
PubMed1979

Epinephrine enhanced renal angiography in the diagnosis of hamartoma (angiomyolipoma): a reevaluation.

The vlue of epinephrine enhanced angiography in the preoperative distinction of isolated hamartoma (angiomyolipoma without stigma of tuberous sclerosis) from hypernephroma has been largely discounted in the past. The authors performed this procedure in 6 patients (4 with isolated hamartoma and 2 with tuberous sclerosis complex). Vasoconstriction of the tumor vessels in the isolated group suggested the benign nature of the hypervascular mass in all cases. Vasoconstriction stronger than that of normal parenchymal vessels suggested the diagnosis of isolated renal angiomyolipoma. This form of pharmacoangiography should be part of the routine preoperative workup of all solid renal masses.

Adenocarcinoma↗
PubMed1977

[Tuberous sclerosis in a premature infant (author's transl)].

A sporadic case of tuberous sclerosis in a stillborn infant is reported. The death at the 31st week of gestation was presumably due to the development of enormous rhabdomyomas of the heart. The typical cerebral lesions were fully developed as in patients decreased later in life. The atypical cells found in the cortical tubers demonstrated ultractructural features of reactive astrocytes. Moreover, they showed innumerable microvillilike projections on their surface and junctional complexes, mostly of the zonula adharens type, reminescent of ependymocytes. The significance of such glio-epithelial cellular features is discussed.

Cerebral Cortex↗
PubMed1978

Hereditary congenital hypopigmented and hyperpigmented macules.

Congenital hypomelanotic and hypermelanotic macules traced in three generations of a family suggested autosomal dominant inheritance. Some affected membbers also showed retarded growth and mental deficiency. Light microscopic findings of "splitdopa" preparations of lesional and normal skin were comparable, except that background staining of keratinocytes in dark macules was higher than in control skin. In light macules it was lower. Ultrastructurally, hypomelanotic skin showed small melanosomes (0.3 mu) that occurred in keratinocytes in melanosome complexes. Hypermelanotic skin revealed large melanosomes (0.6 mu) that were singly distributed in keratinocytes. Melanosome size in normal skin averaged 0.4 mu; distribution pattern was mixed. Melanin granules inside keratinocytes were fully melanized. Hyperpigmented, normal and hypopigmented skin of one person had histological features of black oriental and white skin. This clinical picture could well represent a new neurocutaneous syndrome different from tuberous sclerosis.

Adolescent↗