The genotype-phenotype correlation of hereditary multiple exostoses.
ABSTRACT Hereditary multiple exostoses (HME) is an autosomal dominant condition with a wide spectrum of clinical presentations. The purpose of this study was to determine the relationship between the genotype and the phenotype in HME. Thirty-two affected individuals from 10 families participated in the study. An extensive description of HME phenotype in terms of the anatomical burden of disease involved clinical and radiographic examinations and evaluation of 76 parameters. Mutations were determined by sequencing the EXT 1 and EXT 2 genes. Mutations were found in eight families (26 individuals), with one mutation previously reported in the literature and seven novel mutations. There were seven subjects with an EXT 1 mutation and 16 with an EXT 2 mutation. Patients with EXT 1 mutation were found to have more exostoses, more limb malalignment with shorter limb segments and height, and more pelvic and flatbone involvement. A genotype-phenotype correlation exists in HME, with patients with EXT 1 mutations having a higher degree of anatomical burden.
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ABSTRACT: Multiple osteochondromatosis (MO), or EXT1/EXT2-CDG, is an autosomal dominant O-linked glycosylation disorder characterized by the formation of multiple cartilage-capped tumors (osteochondromas). In contrast, solitary osteochondroma (SO) is a non-hereditary condition. EXT1 and EXT2, are tumor suppressor genes that encode glycosyltransferases involved in heparan sulfate elongation. We present the clinical and molecular analysis of 33 unrelated Latin American patients (27 MO and 6 SO). Sixty-three percent of all MO cases presented severe phenotype and two malignant transformations to chondrosarcoma (7%). We found the mutant allele in 78% of MO patients. Ten mutations were novel. The disease-causing mutations remained unknown in 22% of the MO patients and in all SO patients. No second mutational hit was detected in the DNA of the secondary chondrosarcoma from a patient who carried a nonsense EXT1 mutation. Neither EXT1 nor EXT2 protein could be detected in this sample. This is the first Latin American research program on EXT1/EXT2-CDG.Scientific Reports 09/2014; 4:6407. · 5.08 Impact Factor
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ABSTRACT: Osteochondroma (or osteocartilaginous exostosis) is the most common bone tumor of childhood, with an incidence ranging from 1 to 1.4 per 1,000,000. In the lumbar spine, osteochondromata usually arise from the posterior column at the secondary ossification center and grow away from the spinal canal without causing neurologic deficits. This article reports a rare intraspinal lumbar osteochondroma that compressed the thecal sac, resulting in a hip flexion contracture in an 11-year-old boy. This lumbar, intraspinal, extradural exostosis was confluent with the L3 inferior articular process and compressed the L3 nerve root and thecal sac severely. The patient underwent an en bloc resection of the tumor with a right-sided hemilaminectomy of L3 and L4, a right-sided partial facetectomy at L3 to L4, and an extended resection from the pars intra-articularis of the L2 to the L5 vertebrae. The tumor specimen measured 4.8×3.7×2.5 cm with clear margins. Instrumented posterolateral fusion was completed from L2 to L5 due to iatrogenic instability from the resection. The patient had an uneventful recovery and returned to his normal activities of daily living, including sports. He remains asymptomatic at 54-month follow-up. A solitary lumbar osteochondroma that compresses the spinal cord, resulting in a motor neurological deficit, has not been reported in a pediatric patient. Orthopedic surgeons should be aware of potential intraspinal presentation of osteochondromas. Magnetic resonance imaging is the modality of choice in diagnosing and screening for spinal osteochondromas. These cases can be treated with resection surgery.Orthopedics 04/2014; 37(4):e398-402. · 1.05 Impact Factor
Article: [Hereditary multiple exostoses.][Show abstract] [Hide abstract]
ABSTRACT: Hereditary multiple exostosis (HME) is a hereditary autosomal dominant disease in which multiple exostoses occur. Typically, the exostoses are primarily located at the metaphysis and migrate with continued growth towards the diaphysis. Clinical problems are caused by local pain, impingement of muscle tendons and neurovascular structures, malformation - especially in the forearm - and malignant transformation - especially exostoses at the trunc and pelvic girdle.Der Orthopäde 08/2014; · 0.67 Impact Factor