Features of multiple self‐healing squamous epithelioma and Loeys‐Dietz syndrome in a patient with a novel <i>TGFBR1</i> variant

Sirisomboonwong, Korawan E.; Martindale, Joanne; Keefe, M.; Goudie, David; Poke, Gemma

doi:10.1002/ajmg.a.40652

Cited by 3 publications

(2 citation statements)

References 21 publications

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“…The pathogenic sequence variants included mutations in the extracellular ligand-binding domain and a series of truncating mutations (Figure 4). Since then, TGFBR1 mutations have been reported in 9 other families in the literature [6,[12][13][14][15][16] or found through diagnostic testing (unpublished data). These variants together with variants described in Reference [9] are shown in Figure 4.…”

Section: Pathogenic Tgfbr1 Sequence Variants Cause Mssementioning

confidence: 99%

“…A 56 year old man with a five year history of keratoacanthomas over his arms, face and scalp was found to be carrying a TGFBR1 missense variant (c.664G > A, p.(Gly222Arg)), resulting in substitution of a glycine residue by an arginine at position 222 within the serine/threonine kinase domain [15]. At least seven skin tumors had been excised and diagnosed histologically and he estimated that a further 30 had resolved without treatment.…”

Section: Tgfbr1 Variants In Msse Patients With Aortic Aneurysmsmentioning

confidence: 99%

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Multiple Self-Healing Squamous Epithelioma (MSSE): A Digenic Trait Associated with Loss of Function Mutations in TGFBR1 and Variants at a Second Linked Locus on the Long Arm of Chromosome 9

Goudie

2020

Genes

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MSSE (Ferguson-Smith disease) is a rare familial condition in which multiple skin tumors resembling squamous carcinomas invade locally and then regress spontaneously after several months, leaving disfiguring scars. We review evidence from haplotype studies in MSSE families with common ancestry that the condition is caused by loss of function mutations in TGFBR1 interacting with permissive variants at a second linked locus on the long arm of chromosome 9. The spectrum of TGFBR1 mutations in MSSE and the allelic disorder Loeys Dietz syndrome (characterized by developmental anomalies and thoracic aortic aneurysms) differ. Reports of patients with both MSSE and Loeys Dietz syndrome are consistent with variants at a second locus determining whether self-healing epitheliomas occur in patients with the loss of function mutations found in most MSSE patients or the missense mutations in the intracellular kinase domain of TGFBR1 that characterize Loeys Dietz syndrome.

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Section: Pathogenic Tgfbr1 Sequence Variants Cause Mssementioning

confidence: 99%

Section: Tgfbr1 Variants In Msse Patients With Aortic Aneurysmsmentioning

confidence: 99%

Multiple Self-Healing Squamous Epithelioma (MSSE): A Digenic Trait Associated with Loss of Function Mutations in TGFBR1 and Variants at a Second Linked Locus on the Long Arm of Chromosome 9

Goudie

2020

Genes

Self Cite

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Squamous Cell Carcinoma and its Precursors

Gupta,

Dirschka

2024

Rook's Textbook of Dermatology

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Squamous cell carcinoma (SCC) is the second commonest skin cancer and arises from epidermal keratinocytes or its appendages. The incidence of SCC has increased over the last five decades and is predicted to rise significantly over the next decade. SCC is predominantly a disease of white populations and is especially prevalent in this group in areas of high ambient sun exposure. Predisposing factors include male sex, immune suppression (particularly in those who are organ transplant recipients), sun exposure and advanced age. Precursor lesions such as actinic keratosis and Bowen disease may often be present and patients are more susceptible to developing other UV radiation‐induced skin cancers. SCC has a low rate of metastasis but this increases with SCCs displaying high‐risk features. All SCCs should undergo full clinicopathological correlation and high‐risk SCCs should be managed within a multidisciplinary setting with adequate tumour clearance as the main outcome.

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Coexistence of multiple self-healing squamous epithelioma and features of Loeys–Dietz syndrome caused by a pathogenic missense variant in the kinase domain of TGFBR1

Schirwani,

Suarez,

Sommerlad

et al. 2023

Clinical and Experimental Dermatology

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The transforming growth factor beta receptor 1 (TGFBR1) gene is associated with two distinct clinical presentations, Multiple Self-Healing Squamous Epithelioma (MSSE) also known as Ferguson-Smith syndrome and Loeys-Dietz syndrome. MSSE is characterized by development of multiple self-healing skin tumours that may affect any part of the body. Spontaneous resolution may take several months leaving pitted scars. Most pathogenic variants in MSSE patients are truncating variants distributed throughout the gene or missense variants in the receptor domain of TGFBR1. Missense variants in the kinase domain of TGFBR1 cause LDS which is a connective tissue disorder associated with increased risk of aortic and arterial aneurysms and dissection. There are two reports in the literature of patients with both MSSE and LDS phenotype and a missense variant in the kinase domain of TGFBR1. The patient reported here has MSSE with at least 20 skin tumours (four with perineural invasion) and features of LDS. The patient harbors a heterozygous missense pathogenic variant c.1043G>A p.(Cyst348Tyr) in TGFBR1 which has previously been associated with LDS but not MSSE. This report is consistent with the hypothesis that a variant in a second locus determines whether skin tumours develop in a patient with missense variant in the kinase domain of TGFBR1 associated with LDS. It also highlights the association of more histologically aggressive keratocanthomas associated with perineural invasion in MSSE.

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Features of multiple self‐healing squamous epithelioma and Loeys‐Dietz syndrome in a patient with a novel TGFBR1 variant

Cited by 3 publications

References 21 publications

Multiple Self-Healing Squamous Epithelioma (MSSE): A Digenic Trait Associated with Loss of Function Mutations in TGFBR1 and Variants at a Second Linked Locus on the Long Arm of Chromosome 9

Multiple Self-Healing Squamous Epithelioma (MSSE): A Digenic Trait Associated with Loss of Function Mutations in TGFBR1 and Variants at a Second Linked Locus on the Long Arm of Chromosome 9

Squamous Cell Carcinoma and its Precursors

Coexistence of multiple self-healing squamous epithelioma and features of Loeys–Dietz syndrome caused by a pathogenic missense variant in the kinase domain of TGFBR1

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