EMQN best practice guidelines for the laboratory diagnosis of osteogenesis imperfecta

Osteogenesis imperfecta (OI) comprises a group of inherited disorders characterized by bone fragility and increased susceptibility to fractures. Historically, the laboratory confirmation of the diagnosis OI rested on cultured dermal fibroblasts to identify decreased or abnormal production of abnormal type I (pro)collagen molecules, measured by gel electrophoresis. With the discovery of COL1A1 and COL1A2 gene variants as a cause of OI, sequence analysis of these genes was added to the diagnostic process. Nowadays, OI is known to be genetically heterogeneous. About 90% of individuals with OI are heterozygous for causative variants in the COL1A1 and COL1A2 genes. The majority of remaining affected individuals have recessively inherited forms of OI with the causative variants in the more recently discovered genes CRTAP, FKBP10, LEPRE1,PLOD2, PPIB, SERPINF1, SERPINH1 and SP7, or in other yet undiscovered genes. These advances in the molecular genetic diagnosis of OI prompted us to develop new guidelines for molecular testing and reporting of results in which we take into account that testing is also used to ‘exclude' OI when there is suspicion of non-accidental injury. Diagnostic flow, methods and reporting scenarios were discussed during an international workshop with 17 clinicians and scientists from 11 countries and converged in these best practice guidelines for the laboratory diagnosis of OI

Restrictive dermopathy:Report of 12 cases

Background: This study describes 12 cases of restrictive dermopathy seen during a period of 8 years by the Dutch Task Force on Genodermatology. We present these unique consecutive cases to provide more insight into the clinical picture and pathogenesis of the disease. Observations: Clinical features in more than 85% of these 12 children were prematurity, fixed facial expression, micrognathia, mouth in o position, rigid and tense skin with erosions and denudations, and multiple joint contractures. Ten patients underwent histopathologic skin biopsy. The biopsy results showed flattening of rete ridges in all 10 patients, a thin dermis with collagen aligned parallel to the epidermis in 9 patients, and poorly developed dermal appendages in 9 patients. Additional findings in individual patients included blepharophimosis, inguinal skin tear, skin tear in the frontal neck area that developed during delivery, absent eyelashes, a nide ascendent aorta, and dextrocardia. Fibroblast cultures taken from 5 patients did not show abnormal alpha(2) beta(1) and alpha(1) beta(1) integrin expressions. Conclusions: The alleged rarity of restrictive dermopathy may be partially caused by medical unfamiliarity with this entity, despite its characteristic clinical and histopathologic picture. The pathogenesis of the disease still needs to be elucidated