BACKGROUND: The Ehlers-Danlos syndrome (EDS) comprises a group of hereditary 
connective tissue disorders. Periventricular nodular heterotopia (PNH) is a 
human neuronal migration disorder characterised by seizures and conglomerates of 
neural cells around the lateral ventricles of the brain, caused by FLNA 
mutations. FLNA encodes filamin A, an actin binding protein involved in 
cytoskeletal organisation. The amino-terminal actin binding domain (ABD) of 
filamins contains two tandem calponin homology domains, CHD1 and CHD2.
OBJECTIVE: To report clinical and genetic analyses in a Spanish family affected 
by a connective tissue disorder suggestive of EDS type III and PNH.
METHODS: A clinical and molecular study was undertaken in the three affected 
women. Clinical histories, physical and neurological examinations, brain 
magnetic resonance imaging studies, and skin biopsies were done. Genetic 
analysis of the FLNA gene was undertaken by direct sequencing and restriction 
fragment length polymorphism analysis.
RESULTS: Mutation analysis of the FLNA gene resulted in the identification of a 
novel mutation in exon 3 (c.383C-->T) segregating with the combination of both 
syndromes. This mutation results in a substitution of an alanine residue (A128V) 
in CHD1.
CONCLUSIONS: The findings suggest that the Ala128Val mutation causes the dual 
EDS-PNH phenotype. This association constitutes a new variant within the EDS 
spectrum. This is the first description of a familial EDS-PNH association with a 
mutation in FLNA.