Homozygosity mapping and candidate prioritization identify mutations, missed by whole-exome sequencing, in SMOC2, causing major dental developmental defects.

Inherited dental malformations constitute a clinically and genetically heterogeneous group of disorders. Here, we report on a severe developmental dental defect that results in a dentin dysplasia phenotype with major microdontia, oligodontia, and shape abnormalities in a highly consanguineous family. Homozygosity mapping revealed a unique zone on 6q27-ter. The two affected children were found to carry a homozygous mutation in SMOC2. Knockdown of smoc2 in zebrafish showed pharyngeal teeth that had abnormalities reminiscent of the human phenotype. Moreover, smoc2 depletion in zebrafish affected the expression of three major odontogenesis genes: dlx2, bmp2, and pitx2.

Nicolau's syndrome after local glucocorticoid injection.

We report three cases of Nicolau's syndrome induced by intraarticular glucocorticoid injections. Nicolau's syndrome is defined as livedo-like dermatitis secondary to acute arterial thrombosis occurring immediately after intravascular injection of an insoluble drug substance. The cases described by Nicolau occurred in association with injections of oily bismuth suspensions. In 1970s and 1980s, cases occurred with delayed-action penicillin suspensions injected intramuscularly. Typically, the injection is followed immediately by excruciating pain in the buttock, sometimes with syncope. Cyanotic patches and a livedoid pattern develop. Rapid resolution of the pain and slower clearing of the skin changes occur in most patients. We report three typical cases with both severe pain and skin changes. In addition, two other patients had incomplete variants without skin abnormalities. Each of these five patients had received an injection in or about a joint of a glucocorticoid in a crystalline suspension. The pathophysiology of this syndrome probably involves acute vascular spasm related to penetration of microcrystals into a blood vessel.