Family study of inherited syndrome with multiple congenital deformities: symphalangism, carpal and tarsal fusion, brachydactyly, craniosynostosis, strabismus, hip osteochondritis.
A syndrome of brachydactyly (absence of some middle or distal phalanges), aplastic or hypoplastic nails, symphalangism (ankylois of proximal interphalangeal joints), synostosis of some carpal and tarsal bones, craniosynostosis, and dysplastic hip joints is reported in five members of an Italian family. It may represent a previously undescribed autosomal dominant trait. (+info)
Diaphyseal medullary stenosis with malignant fibrous histiocytoma: a hereditary bone dysplasia/cancer syndrome maps to 9p21-22.
Diaphyseal medullary stenosis with malignant fibrous histiocytoma (DMS-MFH) is an autosomal dominant bone dysplasia/cancer syndrome of unknown etiology. This rare hereditary cancer syndrome is characterized by bone infarctions, cortical growth abnormalities, pathological fractures, and eventual painful debilitation. Notably, 35% of individuals with DMS develop MFH, a highly malignant bone sarcoma. A genome scan for the DMS-MFH gene locus in three unrelated families with DMS-MFH linked the syndrome to a region of approximately 3 cM on chromosome 9p21-22, with a maximal two-point LOD score of 5.49 (marker D9S171 at recombination fraction [theta].05). Interestingly, this region had previously been shown to be the site of chromosomal abnormalities in several other malignancies and contains a number of genes whose protein products are involved in growth regulation. Identification of this rare familial sarcoma-causing gene would be expected to simultaneously define the cause of the more common nonfamilial, or sporadic, form of MFH-a tumor that constitutes approximately 6% of all bone cancers and is the most frequently occurring adult soft-tissue sarcoma. (+info)
Juvenile nephronophthisis associated with retinal pigmentary dystrophy, cerebellar ataxia, and skeletal abnormalities.
A boy aged 9 3/4 years with interstitial nephritis, retinal pigmentary dystrophy, cerebellar ataxia, and skeletal abnormalities is described. The association may be due to a new genetic disorder, since 2 similar cases have been reported. (+info)
Ultrasound screening for hips at risk in developmental dysplasia. Is it worth it?
Between May 1992 and April 1997, there were 20,452 births in the Blackburn District. In the same period 1107 infants with hip 'at-risk' factors were screened prospectively by ultrasound. We recorded the presence of dislocation and dysplasia detected under the age of six months using Graf's alpha angle. Early dislocation was present in 36 hips (34 dislocatable and 2 irreducible). Of the 36 unstable hips, 30 (83%) were referred as being Ortolani-positive or unstable; 25 (69%) of these had at least one of the risk factors. Only 11 (31%) were identified from the 'at-risk' screening programme alone (0.54 per 1000 live births). Eight cases of 'late' dislocation presented after the age of six months (0.39 per 1000 live births). The overall rate of dislocation was 2.2 per 1000 live births. Only 31% of the dislocated hips belonged to a major 'at-risk' group. Statistical analysis confirmed that the risk factors had a relatively poor predictive value if used as a screening test for dislocation. In infants referred for doubtful clinical instability, one dislocation was detected for every 11 infants screened (95% confidence interval (CI) 8 to 17) whereas in infants referred because of the presence of any of the major 'at-risk' factors the rate was one in 75 (95% CI 42 to 149). Routine ultrasound screening of the 'at-risk' groups on their own is of little value in significantly reducing the rate of 'late' dislocation in DDH, but screening clinically unstable hips alone or associated with 'at-risk' factors has a high rate of detection. (+info)
Localization of the gene for sclerosteosis to the van Buchem disease-gene region on chromosome 17q12-q21.
Sclerosteosis is an uncommon, autosomal recessive, progressive, sclerosing, bone dysplasia characterized by generalized osteosclerosis and hyperostosis of the skeleton, affecting mainly the skull and mandible. In most patients this causes facial paralysis and hearing loss. Other features are gigantism and hand abnormalities. In the present study, linkage analysis in two consanguineous families with sclerosteosis resulted in the assignment of the sclerosteosis gene to chromosome 17q12-q21. This region was analyzed because of the recent assignment to this chromosomal region of the gene causing van Buchem disease, a rare autosomal recessive condition with a hyperostosis similar to sclerosteosis. Because of the clinical similarities between sclerosteosis and van Buchem disease, it has previously been suggested that both conditions might be caused by mutations in the same gene. Our study now provides genetic evidence for this hypothesis. (+info)
Identification of the Finnish founder mutation for diastrophic dysplasia (DTD).
Diastrophic dysplasia (DTD) is especially prevalent in Finland and the existence of a founder mutation has been previously inferred from the fact that 95% of Finnish DTD chromosomes have a rare ancestral haplotype found in only 4% of Finnish control chromosomes. Here we report the identification of the Finnish founder mutation as a GT-> GC transition (c.-26 + 2T > C) in the splice donor site of a previously undescribed 5'-untranslated exon of the diastrophic dysplasia sulfate transporter gene (DTDST); the mutation acts by severely reducing mRNA levels. Among 84 DTD families in Finland, patients carried two copies of the mutation in 69 families, one copy in 14 families, and no copies in one family. Roughly 90% of Finnish DTD chromosomes thus carry the splice-site mutation, which we have designated DTDST(Fin). Unexpectedly, we found that nine of the DTD chromosomes having the apparently ancestral haplotype did not carry DTDST(Fin), but rather two other mutations. Eight such chromosomes had an R279W mutation and one had a V340del deletion. We consider the possible implications of presence of multiple DTD mutations on this rare haplotype. (+info)
Terminal osseous dysplasia with pigmentary defects maps to human chromosome Xq27.3-xqter.
We have identified a four-generation family with 10 affected females manifesting one or more of the following features: osseous dysplasia involving the metacarpals, metatarsals, and phalanges leading to brachydactyly, camptodactyly, and other digital deformities; pigmentary defects on the face and scalp; and multiple frenula. There were no affected males. We performed X-inactivation studies on seven affected females, using a methylation assay at the androgen receptor locus; all seven demonstrated preferential inactivation of their maternal chromosomes carrying the mutation, and two unaffected females showed a random pattern. These findings indicate that this disorder is linked to the X chromosome. To map the gene for this disorder, we analyzed DNA from nine affected females and five unaffected individuals, using 40 polymorphic markers evenly distributed throughout the X chromosome. Two-point and multipoint linkage analyses using informative markers excluded most of the X chromosome and demonstrated linkage to a region on the long arm between DXS548 and Xqter. A maximum LOD score of 3.16 at recombination fraction 0 was obtained for five markers mapping to Xq27.3-Xq28. The mapping data should facilitate the identification of the molecular basis of this disorder. (+info)
Effects of massive doses of ergocalciferol plus cholesterol on pregnant rats and their offspring.
Ergocalciferol (320,000 or 480,000 IU/kg) plus cholesterol (60 mg/kg) in olive oil solution was administered daily on 1, 2, or 4 consecutive days to pregnant rats from 9,10, 14, or 18 of gestation. The control animals received only olive oil. Disseminated lesions of metastic calcinosis were found in various tissues, in the coronary arteries and myocardium, in the media of the abnormal aorta, in the lung and pleura, in the gastoinstestinal tract, and in the kidney. This is in contrast to the atherosclerosis described in nonpregnant rats fed a similiar diet. A significant decline in maternal weight as well as a high rate of morbidity and mortality was observed. In mothers killed on day 22 of pregnancy, fetal and placental growths appeared significantly retarded suggesting a direct effect of the steroid or its more active metabolite, 1,25-dihydroxycholecalciferol, on the fetus or the trophoblastic tissue. Fetal bone lesionsassociated with a generalized retardation of ossification, placental edema, or calcification accompanied by a loss of the normal structure of the placenta and degenerative manifestation at this level were observed. Moreover, we noted a striking alteration of the fetal face in 33-39% of experimental fetuses, called by us carnival fetuses. (+info)