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The determination of susceptibility to malignant hyperthermia (MH) by genetic investigation is a controversial issue because of the genetic heterogeneity of this disorder. The requirement for such an approach in MH diagnosis is a strong correlation between MH-associated genetic abnormalities and phenotypic findings in the in vitro contracture test (IVCT). After a severe clinical MH crisis during general anaesthesia a patient was diagnosed by the IVCT in which susceptibility to MH was confirmed. Genetic screening for MH-related mutations in the RYR1 gene revealed the presence of a homozygous 1840C-->T base exchange (Arg614Cys substitution) in this patient. A specific search for this defect in 20 relatives led to the identification of a total of 11 Arg614Cys mutations. Of these, 10 were heterozygous (including both parents) and one was homozygous (sister). Further IVCTs were subsequently performed on the parents of the index patient, the homozygous sister and all relatives who did not carry the Arg614Cys in order to determine the genotype/phenotype correlation. After analysing these data, and because of the strong correlation between clinical, phenotypic, and genetic results in the index patient, we assigned the diagnosis 'MHS' to all the remaining Arg614Cys mutation carriers of that family without performing the IVCT.

We report on a 29-year-old woman with a history of five spontaneous abortions and a balanced complex chromosome rearrangement (CCR) involving break points between chromosomes 8, 11, and 12. Fluorescence in situ hybridisation (FISH) in combination with giemsa trypsin banding techniques were essential for the identification of the breakpoints. In addition, the results were confirmed by 24-colour FISH using the spectral karyotyping system (SKY). The karyotype was 46,XX,t(8;11;12)(8qter-->8p10::12p10-->12pter;11pter--> 11q14::8p10-->8pter;12qter-->12p10::11q14-->11qter). Application of SKY facilitated detection of all three chromosomes involved and supported the localisation of the breakpoints by a single time and sample saving investigation.

Background: Several reports of limb defects occurring among infants exposed to chorionic villus sampling (CVS) during pregnancy resulted in concern about the safety of this procedure for prenatal diagnosis. To avoid publication bias and evaluate the true risk of limb defects in a CVS cohort, the World Health Organization initiated international registration of post-CVS limb defects in 1992., Methods: From May, 1992, to May, 1994, 77 infants or fetuses with limb defects from 138 996 pregnancies having CVS were reported to the WHO CVS Registry. These cases were analysed by standardised methods-ie, exclusion of syndromes, inherited disorders, and defects occurring in previable fetuses. The included limb deficiencies were studied by pattern analysis., Findings: Defects of the upper limbs were reported in 64.6%, of the lower limbs in 12.5%, and of both upper and lower limbs in 20.8% of cases. These figures are in agreement with the distribution of limb defects in several large population-based studies. Transverse limb defects occurred in 40.8% and longitudinal defects in 59.2%, compared with 42.7% and 57.3% in an unexposed population., Interpretation: The analysis of this cohort did not show any differences from the background population in the overall frequency or pattern distribution of limb deficiencies. There was also no correlation between gestational age at CVS and severity of defects. Therefore these results do not indicate any increased risk of limb defects after CVS.