Analysis of MLL2 gene in the first Brazilian family with Kabuki syndrome

Most patients with Kabuki syndrome (KS) are the only person in their family with the condition. However, familial cases of KS have been described showing evidence that this syndrome can be inherited as a dominant trait with variable expressivity. We report on two related individuals with facial findings characteristic of KS. The proposita had arched eyebrows, long and upward slanting palpebral fissures, cleft lip and palate, retromicrognathia, brachydactyly of hands and feet, stubby fingers, nail hypoplasia, and prominent finger pads. Her mother had eyebrows with dispersed lateral half, long and upward slanting palpebral fissures, retrognathia, abnormal and posteriorly rotated ears, prominent finger pads, brachydactyly of feet, learning difficulties, and psychomotor development delay. DNA sequencing revealed a novel missense mutation in the MLL2 gene in both the proposita and her mother. The mutation (p.R5432Q) was found in the exon 51, within the SET domain of the gene, which confers methyltransferase activity on the protein. Therefore, the epigenetic and transcriptional regulatory properties of this protein may be altered and this suggests that the mutation is the cause of phenotype observed in both the patient and her mother. The clinical signs and the molecular evidence in this family further support the notion that KS is an autosomal dominant condition with variable expressivity. To our knowledge this is the first report of a Brazilian family with recurrence of this syndrome. (C) 2012 Wiley Periodicals, Inc.

Giant cell bone lesions in the craniofacial region: a diagnostic and therapeutic challenge

Background: Giant cell tumors of bone (GCTs) are common in the long bones, but rare in the craniofacial region, with only 1% of cases occurring in the latter. Clinical, radiological, and anatomical diagnosis of this locally aggressive disease, which occurs in response to trauma or neoplastic transformation, poses a major challenge in clinical practice. Methods: The present study describes a series of 4 cases and highlights the main features of the differential diagnosis and treatment of these lesions: GCT, giant cell reparative granuloma (GCRG), and the brown tumor of hyperparathyroidism. Results: GCT presents as a benign neoplasm, most typically affecting the knees, and rarely in the temporal and sphenoid bones. It is radiologically indistinguishable from GCRG due to its lytic, poorly defined appearance. The distinction can only be made microscopically, as the presence of multinucleated giant cells scattered throughout the stroma and the absence of a history of trauma favor a diagnosis of GCT. The brown tumor of hyperparathyroidism occurs with rapid, localized osteoclast activity secondary to the effects of increased parathyroid hormone (PTH) levels; parathyroid examination is indispensable. Conclusion: The diagnosis and treatment of these lesions poses a major challenge due to their similar clinical presentation and radiological appearance. Accurate diagnosis is essential for definition of appropriate management, as complete resection is the goal in GCT and GCRG to avoid recurrence, whereas the brown tumor often yields to treatment of the underlying hyperparathyroidism.