A diagnostic and management algorithm for individuals with an isolated skin finding suggestive of tuberous sclerosis complex

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

doi:10.1111/bjd.14724

Cited by 13 publications

(11 citation statements)

References 16 publications

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“…While the commonest TSC clinical findings are usually cutaneous and neurological, our index case's phenotype is atypical in that no significant neurological abnormalities were documented throughout various investigations he underwent through the years, and he presented no sign of epilepsy (bearing in mind that no dedicated brain imaging was performed in him). Regarding TSC cutaneous findings as they pertain to our patient, hypomelanotic macules were shown to be the major cutaneous finding at presentation in 28 of 68 TSC patients in a recent series [19] and are reported in over 90% of TSC patients [2]. Accordingly, a minimum of three hypomelanotic macules over 5 mm in diameter is considered a major criterion sufficient to evoke a possible diagnosis of TSC, according to the International Tuberous Sclerosis Complex Consensus Conference [20].…”

Section: Discussionmentioning

confidence: 66%

Atypical tuberous sclerosis complex presenting as familial renal cell carcinoma with leiomyomatous stroma

Bah

Fahiminiya

Bégin

et al. 2018

The Journal of Pathology CR

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We report an atypical tuberous sclerosis complex (TSC) phenotype presenting as familial multiple renal cell carcinomas (RCCs) with (angio)leiomyomatous stroma (RCCLS) (5/7 familial RCCs) on a background of multiple angiomyolipomas, hypopigmented skin macules, and absence of neurological anomalies. In the index case and three relatives, germline genetic testing identified a heterozygous TSC2 missense pathogenic variant [c.2714 G > A, (p.Arg905Gln)], a rare TSC‐associated alteration which has previously been associated with a milder TSC phenotype. Whole‐exome sequencing of five RCCs from the index case and one RCC from his mother demonstrated either unique tumour‐specific deleterious second hits in TSC2 or significant allelic imbalance at the TSC2 gene locus (5/6 RCCs). This study confirms the key tumourigenic role of tumour‐specific TSC2 second hits in TSC‐associated RCCs and supports the notion that RCCLS may be strongly related to abnormalities of the mTOR pathway.

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Section: Discussionmentioning

confidence: 66%

Atypical tuberous sclerosis complex presenting as familial renal cell carcinoma with leiomyomatous stroma

Bah

Fahiminiya

Bégin

et al. 2018

The Journal of Pathology CR

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“…Our findings are relevant to other skin tumor syndromes in which linear or clustered tumors such as basal cell carcinoma may occur 29, 30. We emphasize the need to analyze affected tumor tissue 31 from these patients if blood proves to be mutation-negative to identify genetic mosaicism, which confers a risk of transmission to offspring.…”

Section: Discussionmentioning

confidence: 78%

Diverse presentations of cutaneous mosaicism occur in CYLD cutaneous syndrome and may result in parent-to-child transmission

Arefi

Wilson

Muthiah

et al. 2019

Journal of the American Academy of Dermatology

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BackgroundClusters of rare cylindroma or spiradenoma tumors are a recurrent clinical presentation, yet conventional genetic testing results in individuals with these tumors are frequently normal.ObjectiveTo determine if genetic mosaicism accounts for such cases.MethodsA study of 6 cases from a series of 55 patients who met criteria for diagnostic gene testing for pathogenic CYLD variants over a 5-year period (2012-2017) was performed. A novel genetic assay was used to study DNA from peripheral blood leukocytes and, where possible, matched skin and tumor tissue.ResultsTwo patients had mosaic pathogenic CYLD variants in both the blood and skin. One of these patients transmitted a pathogenic variant to her daughter, and we report the novel phenotype of a contiguous gene deletion syndrome involving CYLD. Two patients had recurrent pathogenic variants in skin tumors from a single cluster but none detectable in the blood.LimitationsThe remaining 2 patients had clinical features of mosaicism, but these cases were not solved with the assays used because of a lack of access of fresh tumor tissue.ConclusionGenetic mosaicism should be considered in patients presenting with clustered cylindromas, because this may inform genetic testing and counseling of these patients.

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“…An algorithm that evaluates individuals presenting with one skin finding suggestive of TSC has been described. 15 Based on clinical diagnostic workup, remaining patients should receive a diagnosis of probable TSC 1-3 and the parents be informed that the likelihood of disease onset and suspicion. 15,16 At the same time, it is also important to note that the cutaneous manifestations of TSC are ever expanding and care givers should be aware of some atypical skin signs that could prompt possibility of TSC.…”

Section: Discussionmentioning

confidence: 99%

Neonatal Tuberous Sclerosis: is skin really the window?

Kulkarni¹,

El-Atawi²,

Elhalik³

2021

JPNC

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We report a case of a neonate who was diagnosed to have intracardiac mass as a fetus and presented with white linear papules that was diagnosed to be Linear Verrucous Epidermal Nevus. Apart from the intracardiac mass, most likely rhabdomyoma, MRI Brain also showed presence of tubers and the Next Generation Sequence Analysis confirmed the diagnosis of Neonatal Tuberous Sclerosis. The neonate remained asymptomatic and was discharged home and remains under close follow up without any symptoms. It is thus suggested that Linear Verrucous Epidermal Nevus, a cutaneous manifestation not described with Tuberous Sclerosis could be considered under the ever-expanding cutaneous signs of Tuberous Sclerosis and should alert the physician toward its possibility.

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A diagnostic and management algorithm for individuals with an isolated skin finding suggestive of tuberous sclerosis complex

Cited by 13 publications

References 16 publications

Atypical tuberous sclerosis complex presenting as familial renal cell carcinoma with leiomyomatous stroma

Atypical tuberous sclerosis complex presenting as familial renal cell carcinoma with leiomyomatous stroma

Diverse presentations of cutaneous mosaicism occur in CYLD cutaneous syndrome and may result in parent-to-child transmission

Neonatal Tuberous Sclerosis: is skin really the window?

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