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American Journal of Medical Genetics.... Aug 2010We report on two sibs with a lethal form of bone dysplasia with distinctive skeletal findings including rhizomelic and mesomelic limb shortening, hooked clavicles,...
We report on two sibs with a lethal form of bone dysplasia with distinctive skeletal findings including rhizomelic and mesomelic limb shortening, hooked clavicles, dumbbell femurs, and absence of talus and calcaneus ossification. Other clinical features include Dandy-Walker malformation, congenital heart defects, joint contractures, genital hypoplasia, and distinctive facial features. These sibs appear to have a previously undescribed skeletal dysplasia, which is most likely inherited in an autosomal recessive fashion.
Topics: Abnormalities, Multiple; Adult; Dandy-Walker Syndrome; Face; Fatal Outcome; Female; Genitalia; Heart Defects, Congenital; Humans; Infant, Newborn; Male; Musculoskeletal Abnormalities; Thumb
PubMed: 20602491
DOI: 10.1002/ajmg.a.33488 -
Pediatric Blood & Cancer Jul 2010Because a sternal mass is often alarming, it is important to identify the clinical features of benign processes.
BACKGROUND
Because a sternal mass is often alarming, it is important to identify the clinical features of benign processes.
PROCEDURE
Data on clinical presentation, diagnostics, treatment and outcome of pediatric patients presenting with a sternal tumor between 2001 and 2009 were collected from medical records.
RESULTS
Among the 1,700 children who were referred to our pediatric-oncology center, 14 presented with a rapidly growing sternal mass. All patients (10 males) were Caucasian and median age was 16 (range: 7-50) months. Reported symptoms were local pain (n = 7) and/or raised body temperature (n = 5). No major preceding traumas were reported. Physical examination revealed solid tumors with a median diameter of 3 (range: 1-4.5) cm in a pre-sternal/para-sternal location. Half of the patients showed red/blue discoloration of the skin. On radiology, dumbbell-shaped lesions extended to the area behind the sternal bone, involving the cartilage, leading to increased distance between ossification centers. Histopathology at diagnosis was available from five patients and showed aspecific chronic or acute inflammation (n = 4) and a reactive osteochondromatous lesion (n = 1). Laboratory infection parameters were not/only slightly raised and microbiologic cultures were negative in all patients. All tumors decreased in size within 1 month, in both patients with and without antibiotics. On physical examination the tumors disappeared within 6 months.
CONCLUSIONS
This study reports 14 young children with a rapidly growing sternal mass due to aseptic inflammation, that we named self-limiting sternal tumor of childhood (SELSTOC). To prevent invasive diagnostic interventions and unnecessary treatment, we advocate a wait-and-see approach with close follow-up in the first weeks.
Topics: Anti-Bacterial Agents; Bone Neoplasms; Child, Preschool; Female; Follow-Up Studies; Humans; Infant; Male; Retrospective Studies; Sternum; Treatment Outcome
PubMed: 20213849
DOI: 10.1002/pbc.22454 -
Environmental Research Oct 2009In developmental toxicity studies, skeleton abnormalities found in fetuses at term are classified as variations or malformations. The relevance of skeleton variations...
In developmental toxicity studies, skeleton abnormalities found in fetuses at term are classified as variations or malformations. The relevance of skeleton variations for human risk assessment, however, is a controversial issue. This paper is a contribution to the discussion on the interpretation of fetal skeleton variations in the context of risk assessment. Dose-response relationships of skeleton variations and malformations induced by three antineoplastic drugs (FUDR: 5-fluoro-2'-deoxyuridine, HU: hydroxyurea and 6-MPr: 6-mercaptopurine-riboside) were evaluated. FUDR (0, 3, 14, 25, 35, 45, 55 and 65mg/kg body wt sc) and HU (0, 250, 300, 350, 400, 450, 500 and 550mg/kg body wt ip) were administered to rats on gestation day 11 (GD 11) while 6-MPr (0, 3, 7, 10 and 14mg/kg body wt sc) was given on GD 11, or on GD 12. Caesarean sections were performed on GD 21 and all fetuses were cleared and stained with alizarin red S for skeleton examination. Drugs given on GD 11 increased the incidence of thoracic and lumbar vertebra (dumbbell-shaped and bipartite ossification center (o.c.) and sternum (misaligned sternebrae) variations in a dose-dependent manner. Occurrence of zygomatic bone fused with maxilla (a variation in our rats) was also increased by HU and 6-MPr (GD 11) but it was not altered by FUDR. Spontaneous occurrence of wavy ribs was reduced by all treatments. Malformations such as cleft palate, tympanic bone absent and tibia absent were also increased in a dose-dependent manner by the three compounds. No observed effect levels (NOEL) for variations, irrespective of the compound administered, were generally lower than NOELs for malformations. In the discussion, we supported the view that any dose-related increase in the incidence of variations should be taken into account for determination of NOELs in routine studies. Increased occurrences of skeleton variations in term fetuses are also to be considered in risk assessment, unless experimental evidence exists that a particular change has no detrimental effect on the animal survival or health after birth or that it does not occur in humans.
Topics: Animals; Antineoplastic Agents; Bone and Bones; Dose-Response Relationship, Drug; Female; Floxuridine; Hydroxyurea; Maternal Exposure; Mercaptopurine; Pregnancy; Rats; Rats, Wistar
PubMed: 19682677
DOI: 10.1016/j.envres.2009.07.013 -
Journal of Bone and Mineral Research :... Feb 2003Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) were measured in a mild case of dyssegmental dysplasia. X-ray pictures of a female...
Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) were measured in a mild case of dyssegmental dysplasia. X-ray pictures of a female baby born vaginally at 39 weeks of gestation showed short, bent, dumbbell-shaped long bones of the limbs and profound dyssegmental ossification in the spine, findings characteristic of dyssegmental dysplasia. When the levels of MMP-1, MMP-2, MMP-9, TIMP-1, and TIMP-2 were measured, the levels of MMP-2 and TIMP-1 were significantly reduced. This case might provide a clue to disclose the etiology of dyssegmental dysplasia.
Topics: Bone Diseases, Developmental; Bone and Bones; Dwarfism; Female; Fetal Blood; Humans; Infant, Newborn; Matrix Metalloproteinase 1; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Phenotype; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2
PubMed: 12568417
DOI: 10.1359/jbmr.2003.18.2.381 -
Neurotoxicology and Teratology 2001We have evaluated the ameliorative effect of vitamin D on fluoride-induced embryotoxicity in pregnant rats. Oral administration of sodium fluoride (NaF; 40 mg/kg body...
We have evaluated the ameliorative effect of vitamin D on fluoride-induced embryotoxicity in pregnant rats. Oral administration of sodium fluoride (NaF; 40 mg/kg body weight) from days 6 to 19 of gestation caused, as compared with control, significantly lowered body weight, feed consumption, absolute uterine weight and number of implantations. As compared with the control, higher incidence of skeletal (presence of wavy ribs, 14th rib, dumbbell-shaped 5th sternebrae, incomplete ossification of skull) and visceral (subcutaneous haemorrhage) abnormalities was recorded in the foetuses of fluoride-treated pregnant rat. Vitamin D (2 ng/0.2 ml olive oil/animal/day po) treatment significantly ameliorated the fluoride-induced reductions in body weight, feed consumption and absolute uterine weight. As compared with fluoride-treated alone, the total percentage of skeletal and visceral abnormalities observed in foetuses was significantly lowered in fluoride plus vitamin D-treated animals. These findings suggest that vitamin D treatment significantly reduced the severity and incidence of fluoride-induced embryotoxicity. The ameliorative effect of vitamin D against skeletal and visceral abnormalities could be due to stimulation of intestinal absorption of calcium and phosphate, thus raising the plasma calcium and phosphate concentrations.
Topics: Abnormalities, Drug-Induced; Animals; Body Weight; Eating; Embryo, Mammalian; Female; Fluorides; Pregnancy; Rats; Rats, Wistar; Teratogens; Vitamin D
PubMed: 11348838
DOI: 10.1016/s0892-0362(00)00123-9 -
Pediatric Radiology Feb 1998"Metatropic dysplasia variants" are a group of bone dysplasias whose skeletal abnormalities are similar to, but milder than, those of classical metatropic dysplasia. The...
BACKGROUND
"Metatropic dysplasia variants" are a group of bone dysplasias whose skeletal abnormalities are similar to, but milder than, those of classical metatropic dysplasia. The genetic and phenotypic heterogeneity has not been thoroughly elucidated.
OBJECTIVE
The objective was to designate a distinct subtype of these metatropic dysplasia variants.
MATERIALS AND METHODS
The subjects were four Japanese patients, two sporadic cases and two siblings, who all had identical skeletal changes. The radiological features in these patients were compared with those of previously reported metatropic dysplasia variants.
RESULTS
Moderate platyspondyly with pear-shaped and/or anterior-tongued vertebral bodies, halberd pelvis, and dumbbell deformity of the tubular bones were regarded as hallmarks of metatropic dysplasia variants. The peculiar skeletal change in our patients was advanced carpal skeletal age in childhood, unlike most patients reported as metatropic dysplasia variants who manifest delayed carpal ossification. Another hallmark was congenital dislocation of the radial heads. A description of a patient with similar skeletal changes was found in the literature.
CONCLUSION
These patients are considered to represent a distinct subgroup of metatropic dysplasia variants. It remains unknown whether the present siblings represent an autosomal recessive trait or an autosomal dominant trait with germinal mosaicism related to increased paternal age.
Topics: Abnormalities, Multiple; Age Determination by Skeleton; Female; Humans; Infant, Newborn; Male; Osteochondrodysplasias; Radius
PubMed: 9472061
DOI: 10.1007/s002470050310 -
The Journal of Bone and Joint Surgery.... Feb 1987Metatropic dwarfism is a rare heritable skeletal dysplasia that is thought to result from a defect in endochondral ossification. Histological studies have been few and...
Metatropic dwarfism is a rare heritable skeletal dysplasia that is thought to result from a defect in endochondral ossification. Histological studies have been few and have yielded inconsistent findings. In addition, no investigator has commented on the structure and function of the perichondral portion of the growth plate in patients who have metatropic dysplasia. To further characterize this disturbance, histological studies were carried out on autopsy specimens from the proximal part of the femur and the iliac crest of a patient who had this disorder. The major findings were: the absence of formation of normal primary spongiosa in the metaphysis; the presence of a thin seal of bone at the chondro-osseous junction, with abnormal metaphyseal vascular invasion and arrest of endochondral growth; and normal-appearing perichondral ring structures with persistence of circumferential growth. These findings suggest an uncoupling of endochondral and perichondral growth and offer an explanation for the dumbbell-shaped morphological structure of the osseous metaphysis that is seen in patients who have metatropic dysplasia. Other observations included prominence of the cartilaginous canals and vascular channels in the reserve zone; clumping of chondrocytes with enhanced staining of the pericellular matrix in the proliferative zone; a decreased ratio of cells to matrix in the hypertrophic zone, with intracellular metachromatic granules and incomplete evolution of chondrocytes; complete absence of an alcian-blue-positive zone of provisional calcification; and, finally, islands of dysplastic chondrocytes in the metaphysis. These abnormalities suggest that metatropic dysplasia is not simply a disorder of endochondral ossification. There appear to be associated defects in the longitudinal proliferation and maturation of chondrocytes and in the production of normal matrix.
Topics: Achondroplasia; Growth Plate; Humans; Infant; Male; Pelvic Bones; Radiography; Spine
PubMed: 3805078
DOI: No ID Found -
American Journal of Medical Genetics Sep 1986We describe the clinical, radiographic, histopathologic, and ultrastructural features of a distinct neonatal lethal chondrodysplasia inherited as an autosomal recessive...
We describe the clinical, radiographic, histopathologic, and ultrastructural features of a distinct neonatal lethal chondrodysplasia inherited as an autosomal recessive trait. The characteristic radiographic findings consist of flattened, hypoplastic vertebral bodies; short ribs; hypoplastic iliac bones with "a snail-like" configuration; short, broad long-bones with dumbbell-like appearance; short and wide fibula; and precocious ossification of the tarsus. Chondro-osseous histology is characteristic with hypervascularity, increased cellular density, and normal size chondrocytes with a centrally located round nucleus and absence of lacunar space. Because of the snail-like radiographic appearance of the pelvis in this disorder, we propose the name "Schneckenbecken dysplasia" (ie, German for snail pelvis).
Topics: Dwarfism; Female; Genes, Lethal; Genes, Recessive; Humans; Infant, Newborn; Male; Osteochondrodysplasias; Pelvis; Radiography
PubMed: 3799723
DOI: 10.1002/ajmg.1320250107