title: Cutaneous venous malformations related to KRIT1 mutation: case report and literature review.
abstract: Cavernous malformations (CMs) are vascular anomalies of the nervous system mostly located in the brain. Cerebral cavernous malformations can present sporadically or familial, as a consequence of an autosomal dominant condition, with incomplete penetrance and variable clinical expression. Occasionally, extraneural manifestations of CMs involving the skin have been described. We report the case of two siblings presenting in adulthood diffuse cutaneous vascular lesions associated with cerebral CMs that, after surgical excision and histopathologic analysis, resulted to cavernous haemangiomas. Genomic DNA was extracted from peripheral blood, and molecular evaluation of KRIT1 gene was performed. Although no signs of neurological impairment were reported, cerebral MRI revealed multiple images in both patients, suggestive of cavernous haemangiomas. The genetic study demonstrated a nonsense mutation (c.535C>T) in the KRIT1 (Krev-1/rap1 interaction trapped 1) gene. Few reports describe extraneural manifestations of Cavernous malformation syndrome (CMs) related to a KRIT1 mutation; these involve the skin and are associated with hyperkeratotic cutaneous capillary-venous malformation. CMs should be suspected in patients developing multiple nodular cutaneous venous lesions in adulthood.
authors.affiliation: Plastic Surgery Department, S. Andrea Hospital, Faculty of Medicine and Psychology, Sapienza University, Rome, Italy, frgrip@hotmail.com.
authors.forename: Francesca Romana
authors.initials: FR
authors.lastname: Grippaudo
authors.forename: Maria
authors.initials: M
authors.lastname: Piane
authors.forename: Matteo
authors.initials: M
authors.lastname: Amoroso
authors.forename: Benedetto
authors.initials: B
authors.lastname: Longo
authors.forename: Silvana
authors.initials: S
authors.lastname: Penco
authors.forename: Luciana
authors.initials: L
authors.lastname: Chessa
authors.forename: Maria
authors.initials: M
authors.lastname: Giubettini
authors.forename: Fabio
authors.initials: F
authors.lastname: Santanelli
mesh_terms: D000368:Aged; D001165:Arteriovenous Malformations; D016543:Central Nervous System Neoplasms / Q000175:diagnosis / Q000235:genetics*; D018389:Codon, Nonsense; D005260:Female; D020786:Hemangioma, Cavernous, Central Nervous System / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D000075927:KRIT1 Protein; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D035781:Siblings; D017445:Skin Diseases, Vascular / Q000175:diagnosis / Q000235:genetics
chemical_list: D018389:Codon, Nonsense; D000075927:KRIT1 Protein; C107928:KRIT1 protein, human; D008869:Microtubule-Associated Proteins; D011518:Proto-Oncogene Proteins