The Dutch ophthalmologist, Jan van der Hoeve, first introduced the terms phakoma/phakomata (from the old Greek word “ϕαχοσ” = lentil, spot, lens-shaped) to define similar retinal lesions recorded in tuberous sclerosis (1920) and in neurofibromatosis (1923). He later applied this concept: (a) to similar lesions in other organs (e.g. brain, heart and kidneys) (1932) and (b) to other disorders (i.e. von Hippel–Lindau disease and Sturge–Weber syndrome) (1933), and coined the term phakomatoses. At the same time, the American neurologist Paul Ivan Yakovlev and psychiatrist Riley H. Guthrie (1931) established the key role of nervous systems and skin manifestations in these conditions and proposed to name them neurocutaneous syndromes (or ectodermoses, to explain the pathogenesis). The Belgian pathologist, Ludo van Bogaert, came to similar conclusions (1935), but used the term neuro-ectodermal dysplasias. In the 1980s, the American paediatric neurologist Manuel R. Gomez introduced the concept of “hamartia/hamartoma” instead of phakoma/phakomata. “Genodermatoses” and “neurocristopathies” were alternative terms still used to define these conditions. Nowadays, however, the most acclaimed terms are “phacomatoses” and “neurocutaneous disorders”, which are used interchangeably. Phacomatoses are a heterogeneous group of conditions (mainly) affecting the skin (with congenital pigmentary/vascular abnormalities and/or tumours), the central and peripheral nervous system (with congenital abnormalities and/or tumours) and the eye (with variable abnormalities). Manifestations may involve many other organs or systems including the heart, vessels, lungs, kidneys and bones. Pathogenically, they are explained by interplays between intra- and extra-neuronal signalling pathways encompassing receptor-to-protein and protein-to-protein cascades involving RAS, MAPK/MEK, ERK, mTOR, RHOA, PI3K/AKT, PTEN, GNAQ and GNA11 pathways, which shed light also to phenotypic variability and overlapping. We hereby review the history, classification, genomics, clinical manifestations, diagnostic criteria, surveillance protocols and therapies, in phacomatoses: (1) predisposing to development of tumours (i.e. the neurofibromatoses and allelic/similar disorders and schwannomatosis; tuberous sclerosis complex; Gorlin–Goltz and Lhermitte–Duclos–Cowden syndromes); (2) with vascular malformations (i.e. Sturge–Weber and Klippel–Trenaunay syndromes; megalencephaly/microcephaly–capillary malformation syndromes; CLOVES, Wyburn–Mason and mixed vascular nevus syndromes; blue rubber bleb nevus syndrome; hereditary haemorrhagic telangiectasia); (3) with vascular tumours (von Hippel–Lindau disease; PHACE(S)); (4) with pigmentary/connective tissue mosaicism (incontinentia pigmenti; pigmentary/Ito mosaicism; mTOR-related megalencephaly/focal cortical dysplasia/pigmentary mosaicism; RHOA-related ectodermal dysplasia; neurocutaneous melanocytosis; epidermal/papular spilus/Becker nevi syndromes; PENS and LEOPARD syndromes; encephalocraniocutaneous lipomatosis; lipoid proteinosis); (5) with dermal dysplasia (cerebellotrigeminal dermal dysplasia); and (6) with twin spotting or similar phenomena (phacomatosis pigmentovascularis and pigmentokeratotica; and cutis tricolor).

Introduction to phacomatoses (neurocutaneous disorders) in childhood

Ruggieri M.;Polizzi A.;Marceca G. P.;Catanzaro S.;Pratico A. D.;
2020-01-01

Abstract

The Dutch ophthalmologist, Jan van der Hoeve, first introduced the terms phakoma/phakomata (from the old Greek word “ϕαχοσ” = lentil, spot, lens-shaped) to define similar retinal lesions recorded in tuberous sclerosis (1920) and in neurofibromatosis (1923). He later applied this concept: (a) to similar lesions in other organs (e.g. brain, heart and kidneys) (1932) and (b) to other disorders (i.e. von Hippel–Lindau disease and Sturge–Weber syndrome) (1933), and coined the term phakomatoses. At the same time, the American neurologist Paul Ivan Yakovlev and psychiatrist Riley H. Guthrie (1931) established the key role of nervous systems and skin manifestations in these conditions and proposed to name them neurocutaneous syndromes (or ectodermoses, to explain the pathogenesis). The Belgian pathologist, Ludo van Bogaert, came to similar conclusions (1935), but used the term neuro-ectodermal dysplasias. In the 1980s, the American paediatric neurologist Manuel R. Gomez introduced the concept of “hamartia/hamartoma” instead of phakoma/phakomata. “Genodermatoses” and “neurocristopathies” were alternative terms still used to define these conditions. Nowadays, however, the most acclaimed terms are “phacomatoses” and “neurocutaneous disorders”, which are used interchangeably. Phacomatoses are a heterogeneous group of conditions (mainly) affecting the skin (with congenital pigmentary/vascular abnormalities and/or tumours), the central and peripheral nervous system (with congenital abnormalities and/or tumours) and the eye (with variable abnormalities). Manifestations may involve many other organs or systems including the heart, vessels, lungs, kidneys and bones. Pathogenically, they are explained by interplays between intra- and extra-neuronal signalling pathways encompassing receptor-to-protein and protein-to-protein cascades involving RAS, MAPK/MEK, ERK, mTOR, RHOA, PI3K/AKT, PTEN, GNAQ and GNA11 pathways, which shed light also to phenotypic variability and overlapping. We hereby review the history, classification, genomics, clinical manifestations, diagnostic criteria, surveillance protocols and therapies, in phacomatoses: (1) predisposing to development of tumours (i.e. the neurofibromatoses and allelic/similar disorders and schwannomatosis; tuberous sclerosis complex; Gorlin–Goltz and Lhermitte–Duclos–Cowden syndromes); (2) with vascular malformations (i.e. Sturge–Weber and Klippel–Trenaunay syndromes; megalencephaly/microcephaly–capillary malformation syndromes; CLOVES, Wyburn–Mason and mixed vascular nevus syndromes; blue rubber bleb nevus syndrome; hereditary haemorrhagic telangiectasia); (3) with vascular tumours (von Hippel–Lindau disease; PHACE(S)); (4) with pigmentary/connective tissue mosaicism (incontinentia pigmenti; pigmentary/Ito mosaicism; mTOR-related megalencephaly/focal cortical dysplasia/pigmentary mosaicism; RHOA-related ectodermal dysplasia; neurocutaneous melanocytosis; epidermal/papular spilus/Becker nevi syndromes; PENS and LEOPARD syndromes; encephalocraniocutaneous lipomatosis; lipoid proteinosis); (5) with dermal dysplasia (cerebellotrigeminal dermal dysplasia); and (6) with twin spotting or similar phenomena (phacomatosis pigmentovascularis and pigmentokeratotica; and cutis tricolor).
2020
Diagnosis
Genetics
History
Neurocutaneous disorders
Phacomatoses
Tumours
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11769/486863
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