[Familial spontaneous intracranial hypotension]. / Síndrome de hipotensión intracraneal espontánea de presentación familiar.

INTRODUCTION: Spontaneous intracranial hypotension (SIH) is characterized by orthostatic headache and diffuse dural gadolinium enhancement on magnetic resonance imaging. Spontaneous intracranial hypotension is caused by spinal cerebrospinal fluid leaks and evidence for an underlying generalized connective tissue disorder is found in about two thirds of patients. There had been no familial cases reported to date. CASE REPORT: We describe the case report of three healthy female patients with spontaneous intracranial hypotension who belong to the same family. They have no cutaneous or articular stigmas of connective tissue disease. DISCUSSION: These familial cases of spontaneous SIH suggest that certain underlying genetic susceptibility, probably linked to lower resistance of the spinal meninges, could favor the development of spontaneous intracranial hypotension.

Absence of TGFBR2 mutations in patients with spontaneous spinal CSF leaks and intracranial hypotension.

A heritable connective-tissue-disorder often is suspected in patients with spontaneous spinal CSF leaks and intracranial hypotension, but the nature of the disorder remains unknown in most patients. The aim of this study was to assess the gene encoding TGF-beta receptor-2 (TGFBR2) as a candidate gene for spinal CSF leaks. We searched the TGFBR2 gene for mutations in eight patients with spontaneous spinal CSF leaks who also had other features associated with TGFBR2 mutations, i.e., skeletal features of Marfan syndrome, arterial tortuosity, and(or) thoracic aortic aneurysm. The mean age of these 7 women and 1 man was 38 years (range 14-60 years). We detected no TGFBR2 mutations and conclude that TGFBR2 mutations are not a major factor in spontaneous spinal CSF leaks.

Fibrillin-1 gene analysis of Korean patients with spontaneous CSF hypovolemia.

BACKGROUND: Mutations in different domains of the Fibrillin-1 (FBN1) gene may be responsible for the variable phenotypic expression of Marfan's syndrome that may present with CSF hypovolemia. OBJECTIVES: To evaluate the association between mutations in the Fibrillin-1 (FBN1) gene and spontaneous CSF hypovolemia (SCH) in a Korean population. METHODS: We studied 10 consecutive patients with SCH without clinical characteristics of Marfan's syndrome. The genetic analysis was performed. RESULTS: Direct sequencing analysis of the FBN1 gene identified 15 genetic variations, of which 5 coding (3 synonymous, 2 nonsynonymous) and 8 intronic variations were listed in the single nucleotide polymorphism database (dbSNP). The other 2 variations, c.2728 - 12T > C in intron 21 and c.4582 - 19A > G in intron 35, were also observed in normal controls with estimated frequencies of 0.06 and 0.15, respectively. CONCLUSIONS: We could not identify any FBN1 variations possibly associated with SCH in our study population.

Spontaneous spinal cerebrospinal fluid leaks and minor skeletal features of Marfan syndrome: a microfibrillopathy.

OBJECT: 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.