The Adult Phenotype of Tuberous Sclerosis Complex

Nathan, Neera; Burke, Kristina; Trickett, Cory; Moss, Joel; Darling, Thomas N.

doi:10.2340/00015555-2203

Cited by 8 publications

(8 citation statements)

References 14 publications

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“…This example has been recently demonstrated in TSC, where patients with mild clinically apparent disease in fact harbored serious internal manifestations that caused morbidity and sometimes, mortality. 12, 73 Thus, lifetime surveillance for brain, pulmonary and renal hamartomas is necessary for all patients with TSC, including those with mosaic mutations. 74 While rare, malignant transformation of benign tumors in TSC has reported.…”

Section: Counseling For Prognosis and Managementmentioning

confidence: 99%

Mosaic Disorders of the PI3K/PTEN/AKT/TSC/mTORC1 Signaling Pathway

Nathan

Keppler‐Noreuil

Biesecker

et al. 2017

Dermatologic Clinics

103

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Mosaicism is the presence of two or more genetically distinct cell lineages originating from a single zygote. The skin frequently marks mosaic conditions through migration patterns of a population of mutant cells during embryogenesis. Somatic mutations in genes of the PI3K/PTEN/AKT/TSC/mTORC1 signaling pathway can result in segmental overgrowth, hamartomas, and malignant tumors, given the crucial role of this axis in cell growth. Mosaicism for activating mutations in AKT1 and PIK3CA is responsible for Proteus syndrome and PIK3CA-Related Overgrowth Spectrum, respectively. These frequently exemplify Happle’s patterns of cutaneous mosaicism. Postzygotic mutations in PTEN and TSC1/TSC2 result in mosaic forms of the PTEN Hamartoma Tumor Syndrome and tuberous sclerosis complex, which may present as disseminated or segmental disease. Distinct features observed in these mosaic conditions may be attributed to differences in embryological timing or tissue type harboring the mutant cells. Deep sequencing methods of affected tissue is often necessary to diagnosis these disorders. Oral mTORC1 inhibitors, such as sirolimus and everolimus, are useful for treating tuberous sclerosis complex, and drugs targeting mTORC1 or other points along this signaling pathway are in clinical trials to treat several of these disorders.

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Section: Counseling For Prognosis and Managementmentioning

confidence: 99%

Mosaic Disorders of the PI3K/PTEN/AKT/TSC/mTORC1 Signaling Pathway

Nathan

Keppler‐Noreuil

Biesecker

et al. 2017

Dermatologic Clinics

103

View full text Add to dashboard Cite

show abstract

“…A retrospective review of medical records from patients recruited for studies of TSC and lymphangioleiomyomatosis (LAM) at the National Institutes of Health Clinical Center in Bethesda, MD, U.S.A., from 1998 to 2015, was performed. This cohort was enriched for patients diagnosed with TSC in adulthood, frequently after complications arising from renal angiomyolipomas or LAM . Others were referred to our institution for TSC screening and underwent full TSC diagnostic evaluation.…”

Section: Initial Major Cutaneous Feature In 68 Patients With Tuberousmentioning

confidence: 99%

“…These patients should receive a diagnosis of possible TSC . We suggest that the patient and/or guardians be informed that the likelihood of disease onset for possible TSC is unknown; therefore, relaying this tentative diagnosis to subsequent caregivers is prudent . Some patients with no mutation identified using conventional genetic testing may have intronic mutations or mosaicism, in which a fraction of cells bear the TSC1 or TSC2 mutations.…”

Section: Initial Major Cutaneous Feature In 68 Patients With Tuberousmentioning

confidence: 99%

“…This cohort was enriched for patients diagnosed with TSC in adulthood, frequently after complications arising from renal angiomyolipomas or LAM. 5,6 Others were referred to our institution for TSC screening and underwent full TSC diagnostic evaluation. Written informed consent was obtained according to protocols 00-H-0051, 95-H-0186 and/or 82-H-0032, which were approved by the National Heart, Lung and Blood Institute's institutional review board.…”

mentioning

confidence: 99%

“…We recommend use of this algorithm to guide the evaluation of patients at the first cutaneous sign of TSC so that treatment, preventative measures, disease counselling and/or plan for lifetime follow-up may be swiftly enacted. 4,6,13,14…”

mentioning

confidence: 99%

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