Andersen's syndrome is characterized by periodic paralysis, cardiac arrhythmias, and dysmorphic features. We have mapped an Andersen's locus to chromosome 17q23 near the inward rectifying potassium channel gene KCNJ2. A missense mutation in KCNJ2 (encoding D71V) was identified in the linked family. Eight additional mutations were identified in unrelated patients. Expression of two of these mutations in Xenopus oocytes revealed loss of function and a dominant negative effect in Kir2.1 current as assayed by voltage-clamp. We conclude that mutations in Kir2.1 cause Andersen's syndrome. These findings suggest that Kir2.1 plays an important role in developmental signaling in addition to its previously recognized function in controlling cell excitability in skeletal muscle and heart.

Objective To develop and validate new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups. Methods Candidate variables were assembled from published criteria and expert opinion using consensus methodology. Data were collected from 47 rheumatology, dermatology, neurology and pediatric clinics worldwide. Several statistical methods were utilized to derive the classification criteria. Results Based on data from 976 IIM patients (74% adults; 26% children) and 624 non-IIM patients with mimicking conditions (82% adults; 18% children) new criteria were derived. Each item is assigned a weighted score. The total score corresponds to a probability of having IIM. Sub-classification is performed using a classification tree. A probability cutoff of 55%, corresponding to a score of 5.5 (6.7 with muscle biopsy) “probable IIM”, had best sensitivity/specificity (87%/82% without biopsies, 93%/88% with biopsies) and is recommended as a minimum to classify a patient as having IIM. A probability of ≥90%, corresponding to a score of ≥7.5 (≥8.7 with muscle biopsy), corresponds to “definite IIM”. A probability of <50%, corresponding to a score of <5.3 (<6.5 with muscle biopsy) rules out IIM, leaving a probability of ≥50 to <55% as “possible IIM”. Conclusions The EULAR/ACR classification criteria for IIM have been endorsed by international rheumatology, dermatology, neurology and pediatric groups. They employ easily accessible and operationally defined elements, and have been partially validated. They allow classification of “definite”, “probable”, and “possible” IIM, in addition to the major subgroups of IIM, including juvenile IIM. They generally perform better than existing criteria.

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