Chondrosarcoma in a family with multiple hereditary exostoses.

Multiple hereditary exostoses is an autosomal dominant skeletal disorder in which there are numerous cartilage-capped excrescences in areas of actively growing bone. The condition is genetically heterogeneous, and at least three genes, ext1, ext2 and ext3 are involved. The reported risk for malignant transformation to chondrosarcoma has been from 0.6% to 2.8%. We have reviewed six generations of a family with 114 living adult members, 46 of them with multiple exostoses. Four have had operations for chondrosarcoma, giving the risk for malignant transformation as 8.3% in this family. Clinical and radiological examination revealed two additional patients with a suspicion of malignancy, but in whom the histological findings were benign. Reported elsewhere in detail, genetic linkage analysis mapped the causative gene to chromosome 11 and molecular studies revealed a guanine-to-thymine transversion in the ext2 gene. Patients with multiple hereditary exostoses carry a relatively high risk of malignant transformation. They should be informed of this possibility and regularly reviewed.

A novel splice site mutation of the EXT2 gene in a Finnish hereditary multiple exostoses family. Mutations in brief no. 197. Online.

Hereditary multiple exostoses is a dominantly inherited disease characterized by multiple benign osteochondromas. The affected individuals have an increased risk of developing sarcoma. A large Finnish family with hereditary multiple exostosis was analyzed to find the disease-causing mutation. Blood samples were obtained from 35 family members, including 21 affected and 14 unaffected individuals. Using 2-point linkage analysis the EXT phenotype was shown to be linked to the recently cloned EXT2 gene on chromosome 11p11. The coding region of the gene was sequenced and a previously unreported splice site mutation found. This G to T transversion within a 5-prime splice donor site following exon 6 was shown to cause aberrant splicing of RNA. The described change is considered to be a novel disease-causing mutation in the EXT2 gene.

Gains, losses, and amplifications of DNA sequences evaluated by comparative genomic hybridization in chondrosarcomas.

Comparative genomic hybridization was used to search for previously unknown gains and losses of DNA sequences along all chromosome arms in 29 chondrosarcoma specimens obtained from 23 patients. Extensive genetic aberrations, with a mean of 6 changes per tumor (range, 1 to 24), were detected in 21 of the 29 samples analyzed (72%). The majority of these changes were gains of whole chromosomes or whole chromosome arms. Gains of DNA sequence copy number were most frequent at 20q (38%), 17p (38%), 20p (31%), 1cen-q24 (28%), and 14q23-qter (28%). High-level amplifications of small chromosome regions were sporadic, detected in only 17% of the samples. The only recurrent high-level amplification, seen in two tumors (7%), affected the minimal common region 12cen-q15. Other amplifications, each encountered only once, involved 1p33-p35, 2p23-pter, 4p, 6p22-pter, 18q12-q22, 19p13.2, 19q13.2, and 20q13.1. Losses of DNA sequences were rare and were most commonly observed at 6cen-q22 (17%) and 9p (17%).

Straight leg raising test and lumbar cerebrospinal fluid levels of vasoactive intestinal polypeptide and somatostatin in patients with low back pain.

STUDY DESIGN: Straight leg raising was recorded before myelography in 77 patients. At myelography, samples of cerebrospinal fluid were drawn and later analyzed for neuropeptides vasoactive intestinal polypeptide and somatostatin. OBJECTIVES: The study sought to examine correlations, if any, between a positive straight leg raising test and cerebrospinal fluid neuropeptide levels. METHODS: The straight leg raising test was recorded for all patients before a myelography examination was performed because of intractable leg pain symptoms. Forty-seven of the patients were men and 30 were women. Cerebrospinal fluid samples were obtained from all patients upon myelography. Levels of the neuropeptides vasoactive intestinal polypeptide and somatostatin were analyzed in a blind manner by radioimmunoassay, using commercially available radioimmunoassay kits. RESULTS: The results are compatible with previous observations that suggest cerebrospinal neuropeptide levels are altered in conjunction with neural injury or pain syndromes. In the present mixed back pain patient population, which included radicular pain symptoms due to disc herniation and lumbar stenosis, alterations in vasoactive intestinal peptide levels in particular were observed with a positive straight leg raising test. CONCLUSIONS: Nerve root injury, as suggested by a positive straight leg raising test, appears to be neurochemically linked to altered cerebrospinal fluid vasoactive intestinal peptide levels.