Else Merckoll

Long-term muscular outcome and predisposing and prognostic factors in juvenile dermatomyositis: A case–control study

To compare muscle strength, physical health, and HLA–DRB1 allele carriage frequencies in patients with longstanding juvenile dermatomyositis (DM) with that of controls, and to determine the presence of and risk factors for muscle weakness and magnetic resonance imaging (MRI)–detected muscle damage in juvenile DM patients.

Radiographic classification of glenohumeral arthrosis

We studied the interobserver agreement of two radiographic classification systems for evaluation of glenohumeral arthrosis in 40 patients at long-term follow-up after the Eden Hybbinette operation for habitual dislocation of the anterior shoulder. Both observers agreed that none of the patients had severe arthrosis. The Samilson-Prieto system showed agreement using the classification in 35 of 40 operated shoulders (kappa 0.76). The Kellgren-Lawrence system showed agreement using the classification in 23 of 40 operated shoulders (kappa 0.36). The rate of arthrosis in the operated shoulder ranged from 0.2 to 0.6, depending on the classification system and the observer. None of the patients without arthrosis, but one fifth of those with arthrosis reported pain. The Samilson-Prieto classification is preferable because it is simple to use and has excellent interobserver agreement.

A novel type of rhizomelic chondrodysplasia punctata, RCDP5, is caused by loss of the PEX5 long isoform

Import of peroxisomal matrix proteins, crucial for peroxisome biogenesis, is mediated by the cytosolic receptors PEX5 and PEX7 that recognize proteins carrying peroxisomal targeting signals 1 or 2 (PTS1 or PTS2), respectively. Mutations in PEX5 or 12 other PEX genes cause peroxisome biogenesis disorders, collectively named the Zellweger spectrum disorders (ZSDs), whereas mutations in PEX7 cause rhizomelic chondrodysplasia punctata type 1 (RCDP1). Three additional RCDP types, RCDP2-3-4, are caused, respectively, by mutations in GNPAT, AGPS and FAR1, encoding enzymes involved in plasmalogen biosynthesis. Here we report a fifth type of RCDP (RCDP5) caused by a novel mutation in PEX5. In four patients with RCDP from two independent families, we identified a homozygous frame shift mutation c.722dupA (p.Val242Glyfs(∗)33) in PEX5 (GenBank: NM_001131023.1). PEX5 encodes two isoforms, PEX5L and PEX5S, and we show that the c.722dupA mutation, located in the PEX5L-specific exon 9, results in loss of PEX5L only. Both PEX5 isoforms recognize PTS1-tagged proteins, but PEX5L is also a co-receptor for PTS2-tagged proteins. Previous patients with PEX5 mutations had ZSD, mainly due to deficient import of PTS1-tagged proteins. Similarly to mutations in PEX7, loss of PEX5L results in deficient import of PTS2-tagged proteins only, thus causing RCDP instead of ZSD. We demonstrate that PEX5L expression restores the import of PTS2-tagged proteins in patient fibroblasts. Due to the biochemical overlap between RCDP1 and RCDP5, sequencing of PEX7 and exon 9 in PEX5 should be performed in patients with a selective defect in the import of PTS2-tagged proteins.

Satisfactory long-term results after Eden-Hybbinette-Alvik operation for recurrent anterior dislocation of the shoulder: 6 20 years follow-up of 52 patients

We studied the outcome after the Eden-Hybbinette-Alvik operation for recurrent anterior shoulder dislocation in 52 patients after a mean of 14 (6-20) years. Their mean age at operation was 26 years. Redislocation occurred in 2/52 patients. The success rate was 49/52, when rated by the patients, and 38/45, using the Carter-Rowe shoulder score. 44/52 reported no pain, 48/52 no limitations at work and 37/51 no limitations in sports. Mild and moderate arthrosis were found in 24/45 on the operated side and 9/45 on the uninvolved side. None (0/21) of the patients without arthrosis and 5/24 of those with arthrosis in the operated shoulder reported mild or moderate pain.

Axial Spondylometaphyseal Dysplasia Is Caused by C21orf2 Mutations

Axial spondylometaphyseal dysplasia (axial SMD) is an autosomal recessive disease characterized by dysplasia of axial skeleton and retinal dystrophy. We conducted whole exome sequencing and identified C21orf2 (chromosome 21 open reading frame 2) as a disease gene for axial SMD. C21orf2 mutations have been recently found to cause isolated retinal degeneration and Jeune syndrome. We found a total of five biallelic C21orf2 mutations in six families out of nine: three missense and two splicing mutations in patients with various ethnic backgrounds. The pathogenic effects of the splicing (splice-site and branch-point) mutations were confirmed on RNA level, which showed complex patterns of abnormal splicing. C21orf2 mutations presented with a wide range of skeletal phenotypes, including cupped and flared anterior ends of ribs, lacy ilia and metaphyseal dysplasia of proximal femora. Analysis of patients without C21orf2 mutation indicated genetic heterogeneity of axial SMD. Functional data in chondrocyte suggest C21orf2 is implicated in cartilage differentiation. C21orf2 protein was localized to the connecting cilium of the cone and rod photoreceptors, confirming its significance in retinal function. Our study indicates that axial SMD is a member of a unique group of ciliopathy affecting skeleton and retina.

Osteonecrosis after intranasal injection with bevacizumab in treating hereditary hemorrhagic telangiectasia: A case report

Intranasal bevacizumab injections have been used in treating hereditary hemorrhagic telangiectasia (HHT)‐related epistaxis since 2009. It is believed to be a safe and effective treatment for a selected group of HHT patients in reducing frequency and intensity of epistaxis, with few or none adverse effects. In this case report, however, we will describe a patient who developed bilateral osteonecrosis in the knees while undergoing regular intranasal submucosal bevacizumab injections. Although osteonecrosis previously has been documented in patients receiving bevacizumab intravenously in oncologic doses, thus far it has not been reported in patients treated with intranasal submucosal injections. Laryngoscope, 128:593–596, 2018

Radiographic classifications in Perthes disease

Background and purpose — Different radiographic classifications have been proposed for prediction of outcome in Perthes disease. We assessed whether the modified lateral pillar classification would provide more reliable interobserver agreement and prognostic value compared with the original lateral pillar classification and the Catterall classification. Patients and methods — 42 patients (38 boys) with Perthes disease were included in the interobserver study. Their mean age at diagnosis was 6.5 (3–11) years. 5 observers classified the radiographs in 2 separate sessions according to the Catterall classification, the original and the modified lateral pillar classifications. Interobserver agreement was analysed using weighted kappa statistics. We assessed the associations between the classifications and femoral head sphericity at 5-year follow-up in 37 non-operatively treated patients in a crosstable analysis (Gamma statistics for ordinal variables, γ). Results — The original lateral pillar and Catterall classifications showed moderate interobserver agreement (kappa 0.49 and 0.43, respectively) while the modified lateral pillar classification had fair agreement (kappa 0.40). The original lateral pillar classification was strongly associated with the 5-year radiographic outcome, with a mean γ correlation coefficient of 0.75 (95% CI: 0.61–0.95) among the 5 observers. The modified lateral pillar and Catterall classifications showed moderate associations (mean γ correlation coefficient 0.55 [95% CI: 0.38–0.66] and 0.64 [95% CI: 0.57–0.72], respectively). Interpretation — The Catterall classification and the original lateral pillar classification had sufficient interobserver agreement and association to late radiographic outcome to be suitable for clinical use. Adding the borderline B/C group did not increase the interobserver agreement or prognostic value of the original lateral pillar classification.