title: Occurrence of multiple Cerebral Cavernous Malformations in a patient with Neurofibromatosis type 1.
abstract: BACKGROUND
  Neurofibromatosis 1 (NF1) belongs to the autosomal dominant neurocutaneous disorders' group, which mainly includes NF1 and NF2, tuberous sclerosis, von Hippel-Lindau disease and Cerebral Cavernous Malformations (CCMs). NF1 has a major impact on the nervous system, eye, skin, bone or cardiovascular system. Cerebrovascular lesions have been reported in NF1 including aneurysm, pseudoaneurysm, arteriovenous malformations, vascular stenosis or occlusion and Moya moya syndrome.
  
  
  OBJECTIVE
  To report a case of an NF1 patient with multiple CCMs.
  
  
  METHODS
  A 47-year-old man with café-au-lait skin lesions, countless cutaneous neurofibromas, short stature and scoliosis was admitted for progressive spinal cord compression due to histologically proven neurofibroma. Systematic cerebral MRI screening including gradient echo sequences showed multiple asymptomatic CCMs. Screening of CCM1, CCM2 and CCM3 genes was negative while a deleterious frameshift mutation was identified in NF1 gene.
  
  
  CONCLUSIONS
  While single CCM can occur in NF1 patients following radiation exposure, they are only rarely reported in non-irradiated NF1 brain. Even if it could be a fortuitous association, plausible links and explanations exist. If cerebral MRI can be systematic in NF1 to detect asymptomatic gliomas, used protocols in neuroradiology do not usually include gradient echo sequences, the most sensitive test for CCM detection, leading possibly to failure to detect these vascular lesions. More reports having this combination and further investigations of NF1 families will certainly provide a better understanding of links between these 2 phakomatoses, as recently reported with "multiple meningiomas" phenotype associated with multiple CCMs in patients with CCM3 gene mutations or café-au-lait skin lesions in CCM1 mutation carriers.
authors.affiliation: Department of Neurology, Université Paris Sud, Faculté de Médecine Paris Sud, Hôpital de Bicêtre, Assistance Publique, Hôpitaux de Paris (AP-HP), France; Department of Neurosurgery, Université Paris Sud, Faculté de Médecine Paris Sud, Hôpital de Bicêtre, Assistance Publique, Hôpitaux de Paris (AP-HP), France.
authors.forename: K
authors.initials: K
authors.lastname: Rerat
authors.affiliation: Department of Neurosurgery, Université Paris Sud, Faculté de Médecine Paris Sud, Hôpital de Bicêtre, Assistance Publique, Hôpitaux de Paris (AP-HP), France.
authors.forename: F
authors.initials: F
authors.lastname: Parker
authors.affiliation: Department of NeuroRadiology, Université Paris Sud, Faculté de Médecine Paris Sud, Hôpital de Bicêtre, Assistance Publique, Hôpitaux de Paris (AP-HP), France.
authors.forename: G
authors.initials: G
authors.lastname: Nasser
authors.affiliation: INSERM UMR745, Paris Descartes University, France.
authors.forename: D
authors.initials: D
authors.lastname: Vidaud
authors.affiliation: AP-HP, Service de Génétique, Hôpital Lariboisière, France; INSERM UMR 1161, Paris Diderot University, France.
authors.forename: F
authors.initials: F
authors.lastname: Riant
authors.affiliation: AP-HP, Service de Génétique, Hôpital Lariboisière, France; INSERM UMR 1161, Paris Diderot University, France.
authors.forename: E
authors.initials: E
authors.lastname: Tournier-Lasserve
authors.affiliation: Department of Neurology, Université Paris Sud, Faculté de Médecine Paris Sud, Hôpital de Bicêtre, Assistance Publique, Hôpitaux de Paris (AP-HP), France. Electronic address: christian.denier@bct.aphp.fr.
authors.forename: C
authors.initials: C
authors.lastname: Denier
mesh_terms: D001932:Brain Neoplasms / Q000175:diagnosis*; D020786:Hemangioma, Cavernous, Central Nervous System / Q000150:complications / Q000175:diagnosis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009456:Neurofibromatosis 1 / Q000150:complications / Q000175:diagnosis*
keywords: Cavernoma; Cavernous angiomas; Cerebral Cavernous Malformations; Neurocutaneous syndromes; Neurofibromatosis type 1; Phakomatoses