King-Denborough syndrome with and without mutations in the skeletal muscle ryanodine receptor (RYR1) gene.

King-Denborough syndrome (KDS), first described in 1973, is a rare condition characterised by the triad of dysmorphic features, myopathy, and malignant hyperthermia susceptibility (MHS). Autosomal dominant inheritance with variable expressivity has been reported in several cases. Mutations in the skeletal muscle ryanodine receptor (RYR1) gene have been implicated in a wide range of myopathies such as central core disease (CCD), the malignant hyperthermia (MH) susceptibility trait and one isolated patient with KDS. Here we report clinical, pathologic and genetic features of four unrelated patients with KDS. Patients had a relatively uniform clinical presentation but muscle biopsy findings were highly variable. Heterozygous missense mutations in RYR1 were uncovered in three out of four families, of which one mutation was novel and two have previously been reported in MH. Further RyR1 protein expression studies performed in two families showed marked reduction of the RyR1 protein, indicating the presence of allelic RYR1 mutations not detectable on routine sequencing and potentially explaining marked intrafamilial variability. Our findings support the hypothesis that RYR1 mutations are associated with King-Denborough syndrome but that further genetic heterogeneity is likely.

Added utility of gadolinium in the magnetic resonance imaging (MRI) workup of seizures in children younger than 2 years.

The purpose of this study was to evaluate the added utility of gadolinium administration in the magnetic resonance imaging (MRI) workup of seizures in children younger than 2 years. A computerized retrospective search of the radiology information system identified all brain MRI examinations performed at the authors' institution from 1995 to 2002 for children younger than 2 years. Review of the clinical records revealed that 437 of a total 1466 brain magnetic resonance examinations performed on this subset of the pediatric population were performed as part of an initial seizure workup. Magnetic resonance reports and clinical notes were reviewed. MRI studies with enhancing lesions as well as those with equivocal findings were also reviewed in a consensus fashion by 2 senior neuro-radiologists and 2 radiology residents. Contrast administration was rated as essential, helpful, or not helpful for each study. Administration of contrast medium was felt to be essential in formulating a diagnosis in a total of 8 (1.8%) studies, all of which involved documented or highly suspected cases of infection. In an additional 26 cases (5.9%), which included 4 cases of neoplasm, contrast was felt to be useful but not essential in reaching a diagnosis. Contrast was judged not helpful in making the diagnosis in the other 403 studies (92.3%).