Happle-Tinschert syndrome can be caused by a mosaic<i>SMO</i>mutation and is suggested to be a variant of Curry-Jones syndrome: reply from the authors

Khamaysi, Ziad; Sprecher, Eli; Bergman, Reuven

doi:10.1111/bjd.14979

Cited by 5 publications

(6 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Moreover, we suggested that HTS may turn out to be a clinical variant of Curry-Jones syndrome (CJS) that is likewise caused by postzygotic SMO mutations (9). In their reply, however, Khamaysi et al (10) upheld their opinion that the presented case belonged to the spectrum of Gorlin syndrome because the patient "displayed diagnostic criteria for Gorlin syndrome but not for HTS or CJS".…”

mentioning

confidence: 89%

A Postzygotic SMO Mutation Caused the Original Case of Happle–Tinschert Syndrome

Zenker

Tinschert²,

Wieland³

et al. 2018

Acta Derm Venerol

View full text Add to dashboard Cite

show abstract

mentioning

confidence: 89%

A Postzygotic SMO Mutation Caused the Original Case of Happle–Tinschert Syndrome

Zenker

Tinschert²,

Wieland³

et al. 2018

Acta Derm Venerol

View full text Add to dashboard Cite

show abstract

“…1 To date, fifteen additional cases have been described under this designation. [2][3][4][5] The disorder is caused by a postzygotic mutation in the gene smoothened (SMO). 5,6 In several reports, patches of hypertrichosis have been documented.…”

Section: Systematized Naevoid Hypertrichosis May Herald Happle-tinschmentioning

confidence: 99%

Systematized naevoid hypertrichosis may herald Happle–Tinschert syndrome

Hasbún

Reculé

Happle

et al. 2020

Acad Dermatol Venereol

View full text Add to dashboard Cite

“…Khamaysi et al . argued that multiple BCCs were consistent with BCNS but not HTS . Several older reports described BCCs in patients with features suggestive of HTS, while basaloid hamartomas have been described in classic and segmental BCNS with PTCH1 mutations.…”

Section: Discussionmentioning

confidence: 96%

“…Khamaysi et al argued that multiple BCCs were consistent with BCNS but not HTS. 10 Several older reports described BCCs in patients with features suggestive of HTS, [11][12][13] while basaloid hamartomas have been described in classic and segmental BCNS with PTCH1 mutations. Torrelo et al reported a girl with paternally inherited BCNS and mosaicism for a second PTCH1 mutation, with asymmetrical palmar pits, hyper-and hypotrichosis, skeletal abnormalities and hyper-and hypopigmented lesions, confirmed to be BCCs and a basaloid hamartoma.…”

Section: Discussionmentioning

confidence: 99%

Happle–Tinschert, Curry–Jones and segmental basal cell naevus syndromes, overlapping disorders caused by somatic mutations in hedgehog signalling genes: the mosaic hedgehog spectrum

Lovgren

Zhou

Hrčková³

et al. 2019

Br J Dermatol

View full text Add to dashboard Cite

Summary Happle–Tinschert syndrome (HTS) and Curry–Jones syndrome (CJS; OMIM 601707) are rare, sporadic, multisystem disorders characterized by hypo‐ and hyperpigmented skin patches following Blaschko's lines, plus acral skeletal and other abnormalities. The blaschkoid pattern implies mosaicism, and indeed CJS was found in 2016 to be caused by a recurrent postzygotic mutation in a gene of the hedgehog signalling pathway, namely SMO, c.1234C>T, p.Leu412Phe. More recently the original case of HTS was found to carry the same somatic mutation. Despite this genetic and phenotypic overlap, two significant differences remained between the two syndromes. The histological hallmark of HTS, basaloid follicular hamartomas, is not a feature of CJS. Meanwhile, the severe gastrointestinal manifestations regularly reported in CJS had not been described in HTS. We report a patient whose phenotype was entirely consistent with HTS apart from intractable constipation, and a second patient with classic features of CJS plus early‐onset medulloblastoma, a feature of basal cell naevus syndrome (BCNS). Both had the same recurrent SMO mutation. This prompted a literature review that revealed a case with the same somatic mutation, with basaloid follicular hamartomas and other features of both CJS and BCNS. Segmental BCNS can also be caused by a somatic mutation in PTCH1. We thus demonstrate for the first time phenotypic and genetic overlap between HTS, CJS and segmental BCNS. All of these conditions are caused by somatic mutations in genes of the hedgehog signalling pathway and we therefore propose the unifying term ‘mosaic hedgehog spectrum’. What's already known about this topic? Happle–Tinschert syndrome (HTS) and Curry–Jones syndrome (CJS) are rare mosaic multisystem disorders with linear skin lesions. CJS is characterized by severe constipation, which has not previously been reported in HTS. HTS is characterized by basaloid follicular hamartomas, which are not a recognized feature of CJS. The recurrent mosaic SMO mutation found in CJS was recently reported in a patient with HTS. What does this study add? We describe a patient with HTS and intractable constipation, and a case of CJS with medulloblastoma. Both patients had the same recurrent somatic SMO mutation also found in a case reported as segmental basal cell naevus syndrome. SMO functions in the hedgehog pathway, explaining phenotypic overlap between HTS, CJS and mosaic basal cell naevus syndrome. We propose the term ‘mosaic hedgehog spectrum’ for these overlapping conditions.

show abstract

Happle-Tinschert syndrome can be caused by a mosaicSMOmutation and is suggested to be a variant of Curry-Jones syndrome: reply from the authors

Cited by 5 publications

References 7 publications

A Postzygotic SMO Mutation Caused the Original Case of Happle–Tinschert Syndrome

A Postzygotic SMO Mutation Caused the Original Case of Happle–Tinschert Syndrome

Systematized naevoid hypertrichosis may herald Happle–Tinschert syndrome

Happle–Tinschert, Curry–Jones and segmental basal cell naevus syndromes, overlapping disorders caused by somatic mutations in hedgehog signalling genes: the mosaic hedgehog spectrum

Contact Info

Product

Resources

About