Absence of signs of systemic involvement in four patients with bilateral multiple facial angiofibromas

Abstract

Facial angiofibromas are a major diagnostic sign for tuberous sclerosis (TS) and MEN1, and the former is probably the first disease to be considered by a geneticist when such lesions are found. They occur in up to 90% of persons with TS and 40-80% of individuals with MEN1. Early onset facial angiofibromas that are not associated with any other systemic sign appear to be unusual, and their occurrence can leave the clinician with some uncertainty as to their significance, as well as how to proceed. In this article we describe four patients with what appear to be isolated, bilateral facial angiofibromas. We discuss the significance of these lesions with respect to the conditions in which they have been seen, review prior reports of apparently isolated angiofibromas, and provide some rough calculations as to how likely it would be for an underlying systemic condition to be overlooked after different levels of investigation have been performed. We also look at some aspects of the financial cost/benefit ratio of further investigation of TS beyond a clinical examination.

Skin Lesions in Hereditary Endocrine Tumor Syndromes

“…Of note, besides MEN 1 and TSC, multiple facial angiofibromas may be a feature of another genetically inherited tumor-predisposing syndrome, Birt-Hogg-Dubé syndrome (8,13,14). Only rarely have multiple facial angiofibromas been reported to occur in young persons as an idiopathic, isolated finding (15).…”

Multiple eruptive angiofibromas in a 14‐year‐old girl

“…Im Gegensatz zu diesen "syndromalen" Angiofibromen können multiple Angiofibrome in seltenen Fällen auch isoliert außerhalb eines syndromalen Kontextes [13] auftreten. Bislang existiert nur ein weiterer ähnlicher Fallbericht [14].…”

“…Immunhistochemisch zeigte sich in den Angiofibromen dieses Patienten eine fehlende Expression von Hamartin und Tuberin, welche sich ansonsten bei tuberöser Sklerose meist bei der pulmonalen Lymphangioleiomyomatose und renalen Angiomyolipomen, seltener bei kutanen Läsionen, findet. Möglicherweise spielen in kutanen Hamartomen eine epigenetische Regulation und ein Mosaizismus eine größere Rolle [9,13,15]. In unserem Fall lagen keine genomischen TSC1oder TSC2-Mutationen in bekannten Hotspot-Regionen vor, und ein Expressionsverlust für die Proteine Hamartin und Tuberin war nicht zu verzeichnen.…”

Isolated and unilateral facial angiofibromas revealing a type 1 segmental postzygotic mosaicism of tuberous sclerosis complex with c.4949_4982del TSC 2 mutation

“…Dear Editor , Facial angiofibromas (FAs) are common cutaneous manifestations of tuberous sclerosis complex (TSC), typically occurring as bilateral and symmetric facial papules. To date, unilateral FAs have been reported in 16 cases . Most authors have hypothesised that unilateral FAs are a segmental form of TSC mosaicism, but this hypothesis has not been proven.…”

“…Multiple FAs are one of the major features of TSC, but they cannot be considered pathognomonic when isolated, indicating only a ‘possible’ diagnosis of TSC . Indeed, multiple FAs (> 3) are also one of the cutaneous signs of multiple endocrine neoplasia type 1 and may be present, although more rarely, in Birt–Hogg–Dubé syndrome and neurofibromatosis type 2 . Thus, a segmental manifestation of these genodermatoses could not be formally excluded.…”