title: Spontaneous spinal cerebrospinal fluid leaks and minor skeletal features of Marfan syndrome: a microfibrillopathy.
abstract: OBJECTIVE
  Spontaneous spinal cerebrospinal fluid (CSF) leaks are increasingly recognized as a cause of postural headaches. The authors examined a group of patients suffering from spontaneous spinal CSF leaks who also had minor skeletal features of Marfan syndrome for abnormalities of fibrillin-containing microfibrils.
  
  
  METHODS
  Patients with spontaneous CSF leaks were evaluated for the clinical characteristics of connective tissue disorders. Skin biopsies were obtained in three patients with skeletal manifestations that constitute part of the Marfan syndrome phenotype. Cultured fibroblasts were studied for fibrillin-1 synthesis and incorporation into the extracellular matrix (ECM) by performing quantitative metabolic labeling and immunohistochemical analysis. Among 20 consecutive patients found to have spinal CSF leaks, four (20%) exhibited minor skeletal features of Marfan syndrome, but lacked any ocular or cardiovascular abnormalities. The mean age of these patients (30 years) was lower than that of the 16 patients without skeletal abnormalities (44 years; p = 0.01). Abnormalities in fibrillin-1 metabolism and immunostaining were detected in all three patients with the skeletal abnormalities who underwent examination, but not in a control patient without these skeletal manifestations.
  
  
  CONCLUSIONS
  Twenty percent of patients who experience spontaneous spinal CSF leaks have minor skeletal features of Marfan syndrome. The authors demonstrated abnormalities in fibrillin-1 protein deposition in all patients examined, but only one person was found to have a fibrillin-1 abnormality typically found in classic Marfan syndrome. The results indicate that there is a heterogeneous involvement of other components of ECM microfibrils at the basis of this cerebrospinal manifestation. In addition, the authors identified a connective-tissue etiological factor in a group of disorders not previously classified as such.
authors.affiliation: Howard Hughes Medical Institute and Department of Genetics, Stanford University School of Medicine, California, USA.
authors.forename: Iris
authors.initials: I
authors.lastname: Schrijver
authors.forename: Wouter I
authors.initials: WI
authors.lastname: Schievink
authors.forename: Maurice
authors.initials: M
authors.lastname: Godfrey
authors.forename: Fredric B
authors.initials: FB
authors.lastname: Meyer
authors.forename: Uta
authors.initials: U
authors.lastname: Francke
mesh_terms: D000328:Adult; D001706:Biopsy; D004252:DNA Mutational Analysis; D005260:Female; D000071838:Fibrillin-1; D000071837:Fibrillins; D005347:Fibroblasts / Q000473:pathology; D019084:Fluorescent Antibody Technique, Indirect; D006261:Headache / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D006801:Humans; D019585:Intracranial Hypotension / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D008297:Male; D008382:Marfan Syndrome / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D008840:Microfilament Proteins / Q000032:analysis / Q000235:genetics; D012867:Skin / Q000473:pathology; D013353:Subdural Effusion / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D054392:Adipokines
chemical_list: D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines