Karl Martin Klein

Publications (2)12.27 Total impact

• Article: Evidence for genetic factors in vasovagal syncope: a twin-family study.

  Karl Martin Klein, San San Xu, Kate Lawrence, Alexandra Fischer, Samuel F Berkovic
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  ABSTRACT: Vasovagal syncope (VVS) is the most frequent type of syncope and a common differential diagnosis of epilepsy. The role of genetic factors in VVS is debated. We performed a twin-family study to clarify this question and to analyze the putative mode of inheritance. Fifty-one same-sex twin pairs where at least 1 had syncope were ascertained. The twins were interviewed via telephone using a standardized questionnaire. Available medical records were obtained. Information on the affected status of first- and second-degree relatives was acquired. There was a trend toward higher casewise concordance in monozygous (MZ, 0.75) than dizygous (DZ, 0.50) twins for any syncope (p = 0.06). Significant and strong effects on concordance between MZ and DZ twins were found for fainting at least twice unrelated to external circumstances (0.71 vs 0.27, p = 0.018) and for syncope associated with typical vasovagal triggers (0.62 vs 0.00, p < 0.001). Twelve of 19 concordant MZ twin pairs reported sparse or no other affected family members whereas in the other 7 pairs multiple close relatives were affected. The twin analysis provides strong evidence for the relevance of genetic factors in VVS. Analysis of the families suggests that complex inheritance (multiple genes ± environmental factors) is usual, with rarer families possibly segregating a major autosomal dominant gene.
  Neurology 08/2012; 79(6):561-5. · 8.31 Impact Factor
• Article: Familial focal epilepsy with variable foci mapped to chromosome 22q12: expansion of the phenotypic spectrum.

  Karl Martin Klein, Terence J O'Brien, Kavita Praveen, Sarah E Heron, John C Mulley, Simon Foote, Samuel F Berkovic, Ingrid E Scheffer
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  ABSTRACT: We aimed to refine the phenotypic spectrum and map the causative gene in two families with familial focal epilepsy with variable foci (FFEVF). A new five-generation Australian FFEVF family (A) underwent electroclinical phenotyping, and the original four-generation Australian FFEVF family (B) (Ann Neurol, 44, 1998, 890) was re-analyzed, including new affected individuals. Mapping studies examined segregation at the chromosome 22q12 FFEVF region. In family B, the original whole genome microsatellite data was reviewed. Five subjects in family A and 10 in family B had FFEVF with predominantly awake attacks and active EEG studies with a different phenotypic picture from other families. In family B, reanalysis excluded the tentative 2q locus reported. Both families mapped to chromosome 22q12. Our results confirm chromosome 22q12 as the solitary locus for FFEVF. Both families show a subtly different phenotype to other published families extending the clinical spectrum of FFEVF.
  Epilepsia 07/2012; 53(8):e151-5. · 3.96 Impact Factor