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:  Publisher    
Abstract/OtherAbstract:
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.European Journal of Human Genetics advance online publication, 3 October 2012; doi:10.1038/ejhg.2012.209.
Authors:
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:  JOURNAL ARTICLE     Date:  2012-10-03
Journal Detail:
Title:  European journal of human genetics : EJHG     Volume:  -     ISSN:  1476-5438     ISO Abbreviation:  Eur. J. Hum. Genet.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9302235     Medline TA:  Eur J Hum Genet     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Cedars Sinai Medical Center, Medical Genetics Institute, Los Angeles, CA, USA.
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