Neuroendocrine pancreatic tumor in a patient with dual diagnosis of tuberous sclerosis complex and basement membrane disease: A case report and review of the literature

Kopadze, S.; Shoshiashvili, Inga; Dumbadze, Anna; Tkemaladze, Tinatin; Kiladze, Ivane

doi:10.1016/j.radcr.2021.08.041

Cited by 2 publications

(3 citation statements)

References 30 publications

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“…To the best of our knowledge, this is the first report of a dual TSC/KBG syndrome because of a single SV, even though dual diagnosis cases for TSC or KBG have already been reported. Kopadze et al (2021) have reported a clinical dual diagnosis case of TSC and basement membrane disease. They found two compound heterozygous variants in COL4A4 (p.Gly774Arg and p.Gly1465Asp) but no variant in either TSC1 or TSC2 .…”

Section: Resultsmentioning

confidence: 99%

Single variant, yet “double trouble”: TSC and KBG syndrome because of a large de novo inversion

Rodrigues Alves Barbosa,

Maroilley,

Diao

et al. 2024

Life Sci. Alliance

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Despite the advances in high-throughput sequencing, many rare disease patients remain undiagnosed. In particular, the patients with well-defined clinical phenotypes and established clinical diagnosis, yet missing or partial genetic diagnosis, may hold a clue to more complex genetic mechanisms of a disease that could be missed by available clinical tests. Here, we report a patient with a clinical diagnosis of Tuberous sclerosis, combined with unusual secondary features, but negative clinical tests includingTSC1andTSC2. Short-read whole-genome sequencing combined with advanced bioinformatics analyses were successful in uncovering a de novo pericentric 87-Mb inversion with breakpoints inTSC2andANKRD11, which explains the TSC clinical diagnosis, and confirms a second underlying monogenic disorder, KBG syndrome. Our findings illustrate how complex variants, such as large inversions, may be missed by clinical tests and further highlight the importance of well-defined clinical diagnoses in uncovering complex molecular mechanisms of a disease, such as complex variants and “double trouble” effects.

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Section: Resultsmentioning

confidence: 99%

Single variant, yet “double trouble”: TSC and KBG syndrome because of a large de novo inversion

Rodrigues Alves Barbosa,

Maroilley,

Diao

et al. 2024

Life Sci. Alliance

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“…Neurocognitive disorders, especially seizures and intellectual disabilities, have historically been seen as hallmarks of TSC due to Vogt’s triad, but four of the reported patients demonstrated no neurocognitive impairment despite limited data, suggesting TSC may present without Vogt’s triad more frequently than once believed [ 37 , 41 , 43 , 45 , 53 ]. One report from 1984 describes a TSC patient with epilepsy who may have had concurrent PNET and RCC, both of which were found on autopsy [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

“…TSC2 mutations were found in 20 cases [ 16 , 17 , 19 , 27 , 34 – 37 , 40 , 44 , 47 , 51 ]. Nonfunctional PNET was found in 51 cases, 45 of which were found incidentally and the remaining six presented with abdominal/back pain secondary to mass effect [ 16 – 19 , 27 , 29 , 34 – 41 , 43 – 45 , 47 , 49 ]. Pediatric patients composed 26 cases [ 16 – 19 , 27 , 34 , 35 , 37 , 39 , 40 , 51 ].…”

Section: Discussionmentioning

confidence: 99%

Malignant tumors in tuberous sclerosis complex: a case report and review of the literature

Liu,

Lele,

Goodenberger

et al. 2024

BMC Med Genomics

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Background Tuberous sclerosis complex (TSC) is a rare, autosomal dominant genetic disease that arises from TSC1 or TSC2 genetic mutations. These genetic mutations can induce the development of benign tumors in any organ system with significant clinical implications in morbidity and mortality. In rare instances, patients with TSC can have malignant tumors, including renal cell carcinoma (RCC) and pancreatic neuroendocrine tumor (PNET). It is considered a hereditary renal cancer syndrome despite the low incidence of RCC in TSC patients. TSC is typically diagnosed in prenatal and pediatric patients and frequently associated with neurocognitive disorders and seizures, which are often experienced early in life. However, penetrance and expressivity of TSC mutations are highly variable. Herein, we present a case report, with associated literature, to highlight that there exist undiagnosed adult patients with less penetrant features, whose clinical presentation may contain non-classical signs and symptoms, who have pathogenic TSC mutations. Case presentation A 31-year-old female with past medical history of leiomyomas status post myomectomy presented to the emergency department for a hemorrhagic adnexal cyst. Imaging incidentally identified a renal mass suspicious for RCC. Out of concern for hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome, the mass was surgically removed and confirmed as RCC. Discussion with medical genetics ascertained a family history of kidney cancer and nephrectomy procedures and a patient history of ungual fibromas on the toes. Genetic testing for hereditary kidney cancer revealed a 5’UTR deletion in the TSC1 gene, leading to a diagnosis of TSC. Following the diagnosis, dermatology found benign skin findings consistent with TSC. About six months after the incidental finding of RCC, a PNET in the pancreatic body/tail was incidentally found on chest CT imaging, which was removed and determined to be a well-differentiated PNET. Later, a brain MRI revealed two small cortical tubers, one in each frontal lobe, that were asymptomatic; the patient’s history and family history did not contain seizures or learning delays. The patient presently shows no evidence of recurrence or metastatic disease, and no additional malignant tumors have been identified. Conclusions To our knowledge, this is the first report in the literature of a TSC patient without a history of neurocognitive disorders with RCC and PNET, both independently rare occurrences in TSC. The patient had a strong family history of renal disease, including RCC, and had several other clinical manifestations of TSC, including skin and brain findings. The incidental finding and surgical removal of RCC prompted the genetic evaluation and diagnosis of TSC, leading to a comparably late diagnosis for this patient. Reporting the broad spectrum of disease for TSC, including more malignant phenotypes such as the one seen in our patient, can help healthcare providers better identify patients who need genetic evaluation and additional medical care.

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Neuroendocrine pancreatic tumor in a patient with dual diagnosis of tuberous sclerosis complex and basement membrane disease: A case report and review of the literature

Cited by 2 publications

References 30 publications

Single variant, yet “double trouble”: TSC and KBG syndrome because of a large de novo inversion

Single variant, yet “double trouble”: TSC and KBG syndrome because of a large de novo inversion

Malignant tumors in tuberous sclerosis complex: a case report and review of the literature

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