Mosaic RASopathies concept: different skin lesions, same systemic manifestations?
J Med Genet
; 61(5): 411-419, 2024 Apr 19.
Article
em En
| MEDLINE
| ID: mdl-38290824
ABSTRACT
BACKGROUND:
Cutaneous epidermal nevi are genotypically diverse mosaic disorders. Pathogenic hotspot variants in HRAS, KRAS, and less frequently, NRAS and BRAF may cause isolated keratinocytic epidermal nevi and sebaceous nevi or several different syndromes when associated with extracutaneous anomalies. Therefore, some authors suggest the concept of mosaic RASopathies to group these different disorders.METHODS:
In this paper, we describe three new cases of syndromic epidermal nevi caused by mosaic HRAS variants one associating an extensive keratinocytic epidermal nevus with hypomastia, another with extensive mucosal involvement and a third combining a small sebaceous nevus with seizures and intellectual deficiency. Moreover, we performed extensive literature of all cases of syndromic epidermal nevi and related disorders with confirmed pathogenic postzygotic variants in HRAS, KRAS, NRAS or BRAF.RESULTS:
Most patients presented with bone, ophthalmological or neurological anomalies. Rhabdomyosarcoma, urothelial cell carcinoma and pubertas praecox are also repeatedly reported. KRAS pathogenic variants are involved in 50% of the cases, especially in sebaceous nevi, oculoectodermal syndrome and encephalocraniocutaneous lipomatosis. They are frequently associated with eye and brain anomalies. Pathogenic variants in HRAS are rather present in syndromic keratinocytic epidermal nevi and phacomatosis pigmentokeratotica.CONCLUSION:
This review delineates genotype/phenotype correlations of syndromic epidermal nevi with somatic RAS and BRAF pathogenic variants and may help improve their follow-up.Palavras-chave
Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dermatopatias
/
Neoplasias Cutâneas
/
Nevo
Limite:
Humans
Idioma:
En
Revista:
J Med Genet
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Suíça