Document Detail

Vascular and connective tissue anomalies associated with X-linked periventricular heterotopia due to mutations in Filamin A.
MedLine Citation:
PMID:  23032111     Owner:  NLM     Status:  MEDLINE    
Mutations conferring loss of function at the FLNA (encoding filamin A) locus lead to X-linked periventricular nodular heterotopia (XL-PH), with seizures constituting the most common clinical manifestation of this disorder in female heterozygotes. Vascular dilatation (mainly the aorta), joint hypermobility and variable skin findings are also associated anomalies, with some reports suggesting that this might represents a separate syndrome allelic to XL-PH, termed as Ehlers-Danlos syndrome-periventricular heterotopia variant (EDS-PH). Here, we report a cohort of 11 males and females with both hypomorphic and null mutations in FLNA that manifest a wide spectrum of connective tissue and vascular anomalies. The spectrum of cutaneous defects was broader than previously described and is inconsistent with a specific type of EDS. We also extend the range of vascular anomalies associated with XL-PH to included peripheral arterial dilatation and atresia. Based on these observations, we suggest that there is little molecular or clinical justification for considering EDS-PH as a separate entity from XL-PH, but instead propose that there is a spectrum of vascular and connective tissues anomalies associated with this condition for which all individuals with loss-of-function mutations in FLNA should be evaluated. In addition, since some patients with XL-PH can present primarily with a joint hypermobility syndrome, we propose that screening for cardiovascular manifestations should be offered to those patients when there are associated seizures or an X-linked pattern of inheritance.
Eyal Reinstein; Sophia Frentz; Tim Morgan; Sixto García-Miñaúr; Richard J Leventer; George McGillivray; Mitchel Pariani; Anthony van der Steen; Michael Pope; Muriel Holder-Espinasse; Richard Scott; Elizabeth M Thompson; Terry Robertson; Brian Coppin; Robert Siegel; Montserrat Bret Zurita; Jose I Rodríguez; Carmen Morales; Yuri Rodrigues; Joaquín Arcas; Anand Saggar; Margaret Horton; Elaine Zackai; John M Graham; David L Rimoin; Stephen P Robertson
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-10-03
Journal Detail:
Title:  European journal of human genetics : EJHG     Volume:  21     ISSN:  1476-5438     ISO Abbreviation:  Eur. J. Hum. Genet.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-18     Completed Date:  2013-10-17     Revised Date:  2014-05-08    
Medline Journal Info:
Nlm Unique ID:  9302235     Medline TA:  Eur J Hum Genet     Country:  England    
Other Details:
Languages:  eng     Pagination:  494-502     Citation Subset:  IM    
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MeSH Terms
Arteries / pathology*
Base Sequence
Blotting, Western
Cohort Studies
Connective Tissue / pathology*
Contractile Proteins / genetics*
Ehlers-Danlos Syndrome / genetics*,  pathology
Joint Instability / pathology
Microfilament Proteins / genetics*
Molecular Sequence Data
Mutation / genetics
New Zealand
Periventricular Nodular Heterotopia / genetics*,  pathology*
Sequence Analysis, DNA
Skin / pathology*
Grant Support
Reg. No./Substance:
0/Contractile Proteins; 0/Filamins; 0/Microfilament Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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