Fondazione Stella Maris IRCCS
Fondazione Stella Maris IRCCS
De Simone R.,University of Naples Federico II |
Ranieri A.,University of Naples Federico II |
Montella S.,University of Naples Federico II |
Erro R.,University of Naples Federico II |
And 2 more authors.
Neurological Sciences | Year: 2011
Reported prevalence of idiopathic intracranial hypertension without papilledema (IIHWOP) in series of patients with chronic or transformed migraine is significantly higher than expected; yet, IIHWOP is not included among the risk factors for migraine progression. However, several studies provided evidences suggesting that IIHWOP could represent a possible, largely underestimated, risk factor for progression of pain in migraine and, possibly, in other primary headaches. Data from two recent studies, albeit aimed to different end-points, strongly support this hypothesis. In the first study, conducted on a large series of neurological patients without any sign or symptom of raised intracranial pressure (ICP), including chronic headache, the prevalence of bilateral central venous stenosis at magnetic resonance venography (MRV) was 23% and an IIHWOP at opening pressure was found in 48% of this subgroup (11% of the whole sample) while it was not detected in any of the subjects with normal MRV. This indicates that IIHWOP may be much more prevalent than believed in general population and that it can run without any symptom or sign of raised ICP in most of affected subjects. In the second paper, sinus venous stenosis-associated IIHWOP has been found in about one half of a large chronic primary headache patients series with poor response to treatments and in none of those with normal MRV. Moreover, after the diagnostic lumbar puncture, a transient improvement of headache frequency has been observed in the majority of intracranial hypertensive chronic headache subjects. Taken together, the data of these two recent papers rise the following hypothesis: (1) asymptomatic IIHWOP is much more prevalent than expected in general population; (2) IIHWOP is a powerful and largely unrecognized risk factor for progression of pain in primary headache patients; (3) sinus venous stenosis at MRV is a reliable predictor of raised intracranial hypertension also in asymptomatic patients; (4) sinus venous stenosis has a causative role in IIH pathophysiology. These assumptions share a potential high clinical impact and need to be urgently tested in adequately designed controlled studies. © Springer-Verlag 2011.
Scionti I.,University of Modena and Reggio Emilia |
Fabbri G.,University of Modena and Reggio Emilia |
Fiorillo C.,Fondazione Stella Maris IRCCS |
Ricci G.,University of Pisa |
And 10 more authors.
Journal of Medical Genetics | Year: 2012
Background: Facioscapulohumeral muscular dystrophy (FSHD) is considered an autosomal dominant disease with a prevalence of 1 in 20 000. Almost all patients with FSHD carry deletions of integral copies of tandem 3.3 kb repeats (D4Z4) located on chromosome 4q35. However, FSHD families have been reported in which individuals carrying a D4Z4-reduced allele remain asymptomatic. Recently, it has been proposed that the D4Z4-reduced allele is pathogenic only in association with the permissive haplotype, 4APAS. Methods and results: Through the Italian National Registry for FSHD (INRF), genotype-phenotype correlations were extensively studied in 11 non-consanguineous families in which two D4Z4-reduced alleles segregate. Overall, 68 subjects carrying D4Z4-reduced alleles were examined, including 15 compound heterozygotes. It was found that in four families the only FSHD-affected subject was the compound heterozygote for the D4Z4-reduced allele, and 52.6% of subjects carrying a single D4Z4-reduced 4A161PAS haplotype were non-penetrant carriers; moreover, the population frequency of the 4A161PAS haplotype associated with a D4Z4-reduced allele was found to be as high as 1.2%. Conclusions: This study reveals a high frequency of compound heterozygotes in the Italian population and the presence of D4Z4-reduced alleles with the 4A161PAS pathogenic haplotype in the majority of non-penetrant subjects in FSHD families with compound heterozygosity. These data suggest that carriers of FSHD-sized alleles with 4A161PAS haplotype are more common in the general population than expected on the basis of FSHD prevalence. These findings challenge the notion that FSHD is a fully penetrant autosomal dominant disorder uniquely associated with the 4A161PAS haplotype, with relevant repercussions for genetic counselling and prenatal diagnosis.