Cutaneous Venous Malformations Related to KRIT1 Mutation: Case Report and Literature Review
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.
KeywordsVascular lesions KRIT1 gene mutation Anti smooth muscle antibody Skin nodules Surgical excision
Conflict of Interest
All the authors disclose any sponsorship of funding arrangement related to this study and declare that there are no conflicts of interest.
- Bacigaluppi S, Retta SF, Pileggi S, Fontanella M, Goitre L, Tassi L, La Camera A, Citterio A, Patrosso MC, Tredici G, Penco S (2012) Genetic and cellular basis of cerebral cavernous malformations: implications for clinical management. Clin Genet 83(1):7–14. doi: 10.1111/j.1399-0004.2012.01892.x PubMedCrossRefGoogle Scholar
- Bartolomei F, Lemarquis P, Alicherif A, Lepillouer-Prost A, Sayag J, Khalil R (1992) Systematized cavernous angiomatosis with multiple cerebral and cutaneous localization. Rev Neurol (Paris) 148:568–570Google Scholar
- Cavé-Riant F, Denier C, Labauge P, Cécillon M, Maciazek J, Joutel A, Laberge-Le Couteulx S, Tournier-Lasserve E (2002) Spectrum and expression analysis of KRIT1 mutations in 121 consecutive and unrelated patients with cerebral cavernous malformations. Eur J Hum Genet 10(11):733–740PubMedCrossRefGoogle Scholar
- Ortiz L, Costa AF, Bellido ML, Solano F, García-Moreno JM, Gamero MA, Izquierdo G, Chadli A, Falcao F, Ferro J, Salas J, Alvarez-Cermeño JC, Montori M, Ramos-Arroyo MA, Palomino A, Pintado E, Lucas M (2007) Study of cerebral cavernous malformation in Spain and Portugal: high prevalence of a 14 bp deletion in exon 5 of MGC4607 (CCM2 gene). J Neurol Mar 254(3):322–326CrossRefGoogle Scholar
- Sahoo T, Johnson EW, Thomas JW, Kuehl PM, Jones TL, Dokken CG, Touchman JW, Gallione CJ, Lee-Lin SQ, Kosofsky B, Kurth JH, Louis DN, Mettler G, Morrison L, Gil-Nagel A, Rich SS, Zabramski JM, Boguski MS, Green ED, Marchuk DA (1999) Mutations in the gene encoding KRIT1, a Krev-1 ⁄ rap1a binding protein, cause cerebral cavernous malformations (CCM1). Hum Mol Genet 8:2325–2333PubMedCrossRefGoogle Scholar
- Wood MW, White RJ, Kernohan KW (1957) Cavernous hemangiomatosis involving the brain, spinal cord, heart, skin and Kidney: report of a case. Staff Meet Mayo Clinic 32:249–254Google Scholar