January 2026 Research Update

This month, the papers collectively show that kidney growths in tuberous sclerosis complex (TSC), especially renal angiomyolipomas, can cause real-world problems like bleeding, anemia, and pain, and sometimes appear alongside other kidney conditions. Evidence also suggests that treatment with everolimus can preserve overall kidney function over a year, with kidney function improving most in people whose angiomyolipomas shrank more. [1] [2] [3] [4]

In a pooled, post-hoc analysis of two open-label trials in 54 Chinese adults with TSC-related renal angiomyolipoma treated with everolimus for 12 months, average kidney function (estimated glomerular filtration rate, eGFR) stayed about the same from start to 1 year. People whose tumors shrank more were more likely to see eGFR rise over time, and the amount of tumor reduction helped predict the direction of eGFR change. [1]

Several case reports illustrate how angiomyolipomas can be discovered during workups for suspected kidney tumors and can present with bleeding. One 31-year-old woman was diagnosed with TSC after scans showed large angiomyolipomas in both kidneys along with brain changes and facial skin bumps, and she needed multiple blood transfusions due to severe anemia from bleeding around the kidney. [2]

Another case report highlights that different kidney problems can occur at the same time in TSC. A woman in her 70s had angiomyolipomas in both kidneys and also had a high-grade kidney cancer in the right kidney; treatment included embolisation for a bleeding angiomyolipoma, partial removal of the kidney tumor, and everolimus afterward for remaining angiomyolipomas and lung involvement, with stable kidney function and resolved blood in the urine at 6 months. [3]

A separate case report described a 29-year-old woman with a very large angiomyolipoma that had little visible fat on scanning and caused pain and pressure effects; she had the affected kidney removed, needed intensive care and a transfusion after surgery, and reported symptom improvement by 3 months. The authors also emphasized challenges of long-term monitoring and access to specialized testing and medicines in resource-limited settings. [4]

Finally, a pediatric case report broadened the kidney picture beyond angiomyolipomas by describing a 16-month-old boy with early, rapidly progressing cysts in both kidneys and high blood pressure, along with seizures and other classic TSC features. Genetic testing did not identify TSC1 or TSC2 changes on a single exome analysis, and the authors discussed possibilities such as mosaic genetic changes or a contiguous gene syndrome involving TSC2 and PKD1. [5]

For patients and caregivers, these papers add context on why kidney monitoring matters in TSC: kidney angiomyolipomas can sometimes lead to bleeding or anemia and may look like other kidney tumors on scans, and more than one kidney condition can occur in the same person. The everolimus analysis is medium-strength evidence over 1 year and suggests overall kidney function may remain stable, with better kidney function mainly seen in people whose tumors shrink more, but it does not prove the same results for all ages, ancestry groups, or for people with very advanced kidney disease. The case reports describe individual experiences and help illustrate possible complications, but they cannot predict what will happen for most people. [1] [2] [3] [4] [5]

This month, research and clinical reports covered several different ways seizures may be managed in tuberous sclerosis complex (TSC): procedures, implanted devices, and early-stage drug ideas. Overall, the pattern was that different options can reduce seizures in some people, but each comes with different practical tradeoffs, and some evidence is still limited to small or non-human studies. [6] [7] [8]

A systematic review comparing laser interstitial thermal therapy (a minimally invasive laser procedure) with open resective epilepsy surgery in non-tumor epilepsy found open surgery had higher complete seizure freedom overall, while the laser approach had fewer complications and shorter hospital stays. Reoperation rates were reported as similar between approaches in the pooled data. This analysis included people with conditions such as TSC, but it was not specific to TSC alone. [6]

A commentary discussing smart bio-implants and closed-loop neurostimulation in TSC summarized human observations where responsive neurostimulation was linked to lower seizure counts over time for many patients, while also reporting device-related serious events such as infections or lead revisions. It also highlighted non-medical barriers, including cost, scaling up access, and concerns about privacy and data ownership when devices record brain signals. [7]

In animal research, the drug J4 (an ENT1 inhibitor) was tested as a pretreatment before chemically induced seizures in mice, including a Tsc2+/- model. Mice given J4 had lower seizure severity and less evidence of brain cell loss and inflammation signals in the brain, alongside changes in markers linked to nerve-cell signaling and circuit remodeling. Because this work was in mice and used a specific seizure model, it mainly supports a possible direction for future drug development rather than a care option available now. [8]

For patients and caregivers, these papers mainly add context about the range of seizure-care approaches being studied in TSC, from surgery choices to implanted stimulation systems to lab-stage medicines. The most immediately applicable information is that different seizure procedures can involve different tradeoffs (for example, seizure freedom rates versus complications and hospital time), while implanted devices may reduce seizures for some people but can require ongoing monitoring and carry device-related risks. Much of the drug-related work in this group is still preclinical, so it does not yet show how well these approaches work or how safe they are in people with TSC.

Several papers focused on how seizures may show up or be explained in TSC, from unusual symptoms to changes seen in brain tissue. Together, they suggest that seizure symptoms can be non-obvious (such as vomiting), and that inflammation-related pathways in TSC brain lesions may influence how easily seizures occur, although this biology is not yet a treatment. [9] [10]

Two pediatric case reports described vomiting as the first clear seizure sign in children with TSC (one genetically confirmed, the other diagnosed clinically after genetic testing was negative), with brain MRI showing cortical tubers. Long-term video-electroencephalography (EEG) helped connect vomiting to seizure activity in one child, and showed epileptiform activity between seizures in the other; both children achieved seizure control with antiseizure medicines, with one child also receiving everolimus. One child developed significant daytime sleepiness on clobazam, which was later stopped. [9]

A translational study of brain tissue from people with TSC (and a related condition, focal cortical dysplasia type IIb) reported lower levels of GPR32 and Resolvin D1 in lesions compared with control tissue, and these lower levels were linked to higher seizure frequency. In lab experiments, the same pathway was connected to less pro-inflammatory microglial activity and to reduced measures of neuronal excitability, offering a possible explanation for how inflammation signaling and seizure activity may interact in these conditions. [10]

One single-patient case report described a 13-year-old boy with TSC whose self-injurious behavior worsened after starting vigabatrin, even though seizures improved. After the vigabatrin dose was reduced and valproate was added, self-injurious behavior improved substantially, and an eye exam did not show visual field loss in this reported case. Because this is one patient, it cannot show how often this side effect occurs. [11]

These studies matter most for awareness and future research rather than changing care right now. The case reports show that recurrent vomiting or sudden behavioral worsening can sometimes be linked to seizures or seizure medicines in TSC, but single cases cannot predict what will happen for others. The tissue study helps explain why inflammation-related signals in brain lesions might relate to seizure frequency, yet it does not establish a proven test or treatment, so its main value is as background for future work.

Together, these papers show that tuberous sclerosis complex (TSC) may be recognized through a combination of visible skin or mouth findings, prenatal imaging clues, and genetic testing. They also highlight an important gap: some people have very low-level mosaic gene changes that may be missed in standard blood testing, making diagnosis more complicated in some families. [12] [13] [14]

In a retrospective study from Yemen of 49 people diagnosed with TSC, all had skin or mouth findings, including facial angiofibromas, light-colored skin patches, and a thickened "shagreen" skin patch. Oral checks were only documented in 17 people, but most of those had oral fibromas and many had dental enamel pits, suggesting the mouth can also provide visible clues when it is examined. [12]

In a retrospective series of 36 pregnancies where fetal ultrasound showed cardiac rhabdomyoma (a heart tumor that can occur in TSC), several fetuses who had fetal brain MRI showed brain changes suggestive of TSC, and genetic testing found TSC-related gene mutations in some cases. The report also noted that multiple heart tumors were more strongly tied to TSC than a single tumor, and follow-up data showed that some heart tumors shrank or fully regressed within 1 year after birth. [13]

Two case reports described people with low-level mosaic TSC, where the disease-causing gene change was present at very low levels and was easier to find using ultra-deep sequencing in tissue from an accessible lesion (such as an angiofibroma or angiomyolipoma) than by blood alone. In one case, the variant was first detected from a skin lesion biopsy and then confirmed in other tissues; this supports the idea that testing more than one tissue can sometimes clarify a diagnosis and family risk. [14]

For patients and caregivers, this set of studies mainly adds context about how TSC is recognized in different situations: through common skin and mouth features in known TSC, through prenatal detection of heart tumors with follow-up imaging and genetics in some pregnancies, and through special approaches when standard genetic tests do not find an answer. What remains uncertain is how often very low-level mosaicism explains "negative" genetic results in the wider TSC population, and how consistently prenatal heart and brain findings predict TSC across different care settings. [12] [13] [14]

Across these papers, the main pattern was that tuberous sclerosis complex (TSC) can involve body systems that are not always the main focus of routine TSC discussions, including the liver, joints, hormone glands, and the mouth. Most human evidence here came from single-patient case reports, so it mainly helps describe what can happen and how it may be recognized rather than how often it occurs.

In preclinical (lab and mouse) TSC models, higher activity of a protein called KDM6A appeared to push liver scarring (fibrosis) and cell changes linked to scarring through the MAPK/ERK/SNAI1 pathway. Lowering KDM6A reduced scarring markers and also lowered mTORC1 signaling, suggesting these pathways can reinforce each other in TSC-related liver disease. [15]

One case report described a 9-year-old girl with TSC who had multiple hamartomas inside the hip and knee joints that appeared to start from the joint capsule. Magnetic resonance imaging (MRI) and tissue testing supported that these were hamartomas with fatty, fibrous, and vascular components, highlighting a rare musculoskeletal location for TSC growths. [16]

Another case report described an 11-year-old boy with TSC who developed primary hyperparathyroidism, a condition involving overactive parathyroid glands that can raise blood calcium. Imaging suggested more than one parathyroid gland was involved, and after surgery the child had temporary low parathyroid function. [17]

A separate case report described a 12-year-old girl with TSC who had a gum swelling in the mouth that was diagnosed as a giant cell fibroma after removal. The report noted no recurrence at 1 year, and it adds giant cell fibroma as one possible explanation for fibrous-appearing mouth lesions in a person with TSC. [18]

For patients and caregivers, this group of papers mainly serves as background on less common TSC-related issues that may come up in specific situations, such as unusual joint masses, unexpected high-calcium hormone problems, or new mouth growths. The liver fibrosis study is not a human clinical trial, but it clarifies possible biological pathways that researchers may study further. Because three of the four papers are single-patient reports, it remains uncertain how often these problems occur in TSC or which people are most likely to experience them.

This group of papers shows that changes affecting the TSC pathway can appear in different tumor types, sometimes in people with tuberous sclerosis complex (TSC) and sometimes in people without any known inherited condition. Several reports also emphasize that rare tumors can be difficult to classify at first, and deeper tissue and genetic testing may change the diagnosis, which can also change how the tumor is understood. [19] [20] [21] [22] [23]

In malignant perivascular epithelioid cell tumors (PEComas), many tumors used an alternative way to maintain telomeres (a form of chromosome end maintenance), and this was often linked to ATRX gene changes but not always. In a cohort of 32 malignant PEComas, all tumors with ATRX mutations that were tested showed this telomere pattern, yet some tumors showed the pattern even without detectable ATRX changes, suggesting there may be more than one route to the same tumor feature. [24]

Two reported cases of a rare chromophobe thyroid cancer had somatic (tumor-only) TSC2 mutations, and neither patient had a germline (inherited) TSC mutation found. In the accompanying literature review, a substantial portion of the small number of published cases had been reported in people with TSC, and local recurrence was described in some cases, while reported follow-up noted patients were alive. [19]

A separate PEComa report described a fibroma-like PEComa in a 6-year-old girl where testing found a germline TSC2 nonsense mutation, leading to a diagnosis of TSC, and the tumor showed strong GPNMB staining in the tissue. In the review of eight fibroma-like PEComa cases, these tumors were mainly reported in children and were described as behaving in a benign way with no recurrences or spread in the published cases. [20]

In kidney tumor settings, two papers highlighted that tumors with some overlapping appearance can occur with and without inherited syndromes. In four patients with end-stage kidney disease, multifocal low-grade oncocytic renal tumors (including very small microtumors) were found even though the patients had no clinical features of TSC, and these tumors appeared alongside other kidney tumors seen in chronic kidney disease. [22]

In a larger surgical cohort of 527 people with tumors in both kidneys, the tissue types on each side matched fairly often across major kidney cancer categories, and inherited genetic causes were uncommon among those tested. Only 53 people underwent germline testing, and 4 had a pathogenic variant, including 1 person with tuberous sclerosis; no pathogenic variants were found in the bilateral clear cell group. [23]

One pediatric brain tumor case illustrates how an initial tumor label can later change with added molecular testing. An intraventricular tumor first called a subependymal giant cell astrocytoma (SEGA) stayed stable for 4 years on an mTOR inhibitor, then rapidly progressed; re-evaluation reclassified it as an aggressive anaplastic meningioma, with a germline CHEK2 variant and tumor changes in NF1 and TP53, and no germline TSC1/TSC2 defect identified. [21]

One laboratory and animal study, not focused on cancer, examined how the TSC2-mTORC1-HIF-1 alpha pathway can influence how cells change behavior after blood vessel injury. In these models, Oroxylin A reduced vessel wall thickening and shifted cell metabolism by affecting TSC2-related signaling, and forcing HIF-1 alpha activity reversed this effect, supporting this pathway as a control point for cell growth behavior in that setting. [25]

For patients and caregivers, these studies mainly add background about how TSC pathway changes show up across different tumors and why tumor classification can be complex in rare situations. Some reports describe tumors where a TSC gene change was only in the tumor (not inherited), while others describe a tumor that led to discovering inherited TSC, so the same pathway can be involved in different ways. Much of the evidence here comes from small case reports and small series, which means it can highlight possibilities but cannot reliably predict outcomes for an individual person; the lab study is early-stage and does not establish effects in people.