Skeletal Dysplasia Presenting as a Neuromuscular Disorder - Report of a Family with Camurati-Engelmann Syndrome.
Ontology highlight
ABSTRACT:
SUBMITTER: Plaiasu V
PROVIDER: S-EPMC4496766 | biostudies-literature | 2015 Mar
REPOSITORIES: biostudies-literature
Publications
Skeletal Dysplasia Presenting as a Neuromuscular Disorder - Report of a Family with Camurati-Engelmann Syndrome.
Plaiasu Vasilica V Costin Amalia A
Maedica 20150301 1
We report the case of a 28-year-old female with progressive diaphyseal dysplasia, who presented with history of a similar neuromuscular condition. Clinical, radiological and molecular data confirmed Camurati-Engelmann Disease (CED). This is the first Romanian family who was diagnosed with CED. ...[more]
Similar Datasets
Project description:Camurati-Engelmann disease, progressive diaphyseal dysplasia, or diaphyseal dysplasia Camurati-Engelmann is a rare, autosomal dominantly inherited bone disease, characterised by progressive cortical expansion and sclerosis mainly affecting the diaphyses of the long bones associated with cranial hyperostosis. The main clinical features are severe pain in the legs, muscular weakness, and a waddling gait. The underlying cause of this condition remains unknown. In order to localise the disease causing gene, we performed a linkage study in a large Jewish-Iraqi family with 18 affected subjects in four generations. A genome wide search with highly polymorphic markers showed linkage with several markers at chromosome 19q13. A maximum lod score of 4.9 (theta=0) was obtained with markers D19S425 (58.7 cM, 19q13.1) and D19S900 (67.1 cM, 19q13. 2). The disease causing gene is located in a candidate region of approximately 32 cM, flanked by markers D19S868 (55.9 cM, 19q13.1) and D19S571 (87.7 cM, 19q13.4).
| S-EPMC1734563 | biostudies-other
Project description:Camurati-Engelmann disease (CED) is a rare autosomal dominant bone disorder caused by a mutation in transforming growth factor ?1 (TGF?1). The present study aimed to identify a Chinese family with suspected CED based on the clinical symptoms, including pain in extremities, waddling gait, muscle weakness, cortical thickening of the diaphysis of the long bones, and sclerosis of the skull, facial bone, and pelvis. Molecular analysis revealed the presence of the p.Glu169Lys (E169K) mutation in exon 2 of TGF?1 in patients when compared with the controls. Therefore, the Chinese family was diagnosed with CED due to the presence of the E169K mutation. The present study emphasized the importance of clinical and genetic evidence for the diagnosis of CED. The data presented in the present study are of significance to clinicians, as well as genetic counselors, in the prenatal screening of CED.
| S-EPMC5355693 | biostudies-literature
Project description:Camurati-Engelmann disease (CED) is an autosomal dominant progressive diaphyseal dysplasia caused by mutations in the transforming growth factor-beta1 (TGFB1) gene. We report the first Korean family with an affected mother and son who were diagnosed with CED. The proband is a 19-yr-old male with a history of abnormal gait since the age of 2. He also suffered from proximal muscle weakness, pain in the extremities, and easy fatigability. Skeletal radiographs of the long bones revealed cortical, periosteal, and endosteal thickenings, predominantly affecting the diaphyses of the upper and lower extremities. No other bony abnormalities were noted in the skull and spine and no remarkable findings were seen on laboratory tests. The patient's mother had a long-standing history of mild limb pain. Under the impression of CED on radiographic studies, we performed mutation analysis. A heterozygous G to A transition at cDNA position +653 in exon 4 of the TGFB1 gene (R218H) was detected in the patient and his mother.
| S-EPMC2719210 | biostudies-literature
Project description:BackgroundCamurati-Engelmann disease (CED) is a rare genetic skeletal disorder characterized by limb pain, muscle emaciation and weakness, and cortical thickening of the diaphysis of long bones. It is caused by mutations in the transforming growth factor beta 1 (TGFB1) (type I) or other unknown gene(s) (type II). We present 8 consecutive patients with type I CED.MethodsWe retrospectively reviewed medical records and radiographs of type I CED patients with special reference to the mode of presentation, process of diagnostic work-up, and disease course. They were 4 sporadic patients, and two pairs of mother and son.ResultsWe categorized the mode of presentation into three groups. Group I had 4 patients who mainly presented with motor disturbances in young age. They drew medical attention for waddling gait, awkward ambulation or running, difficulty in going upstairs, or a positive Gower's sign at age 4 to 6 years. Subsequent development of limb pain and radiographic abnormality led to the diagnosis of CED at age 6 to 29 years. Group II had 3 patients who mainly presented with limb pain at age 15, 20, and 54 years, respectively. Radiographic evaluation and molecular genetic test led to the diagnosis of CED. The remaining 1 patient (group III) was asymptomatic until age 9 years when bony lesions at the tibiae were found incidentally. For the last 10 years, he intermittently complained of leg pain in the morning or after sports activities, which did not interfere with daily life. All the patients in group I showed a body mass index in the underweight range (< 18.4 kg/m2). At the latest follow-up, 4 patients in groups I and II required medication for the limb pain.ConclusionsCED presents with a wide range of severity. Awareness of this rare disease entity may be the key to timely correct diagnosis. This disease entity should be considered in the differential diagnosis of limb pain or motor disturbance in children to avoid unnecessary diagnostic work-up.
| S-EPMC5334020 | biostudies-literature
Project description:Camurati-Engelmann disease (i.e., progressive diaphyseal dysplasia) is an extremely rare autosomal dominant bone disorder. The most common clinical manifestations were chronic skeletal pain, waddling gait, muscular weakness.We described that a 27-year-old male with a 1-year history of intermittent tetany was referred for bone scintigraphy. The whole body bone scan images showed abnormal increased uptake of the tracer in the long bones of the upper and lower extremities as well as in the skull.Combined the family history, the findings of the images and the genetic study, the diagnosis of Camurati-Engelmann disease was confirmed.The patient responded well to the treatment of calcium gluconate.Bone scintigraphy would be helpful in the diagnosis and assessing the severity of Camurati-Engelmann disease.
| S-EPMC5502140 | biostudies-literature
Project description:A 23-year-old woman presented with bilateral papilloedema in a setting of Camurati-Engelmann disease (CED). She was investigated with neuroimaging showing no optic nerve canal stenosis or jugular vein canal compromise. Her MRI venogram was normal. Her opening pressure at lumbar puncture and serum alkaline phosphatase were raised. Her papilloedema resolved with long-term use of acetazolamide. We believe that our patient suffered from raised intracranial pressure directly as a result of decreasing intracranial volume secondary to CED.
| S-EPMC4550960 | biostudies-other
Project description:Camurati-Engelmann disease (CED) is a rare disorder included in the group of craniotubular hyperostosis diseases. Corticosteroids are used for pain management in CED, but in refractory or corticosteroid-non-tolerant patients, pain management is limited. We report the case of a woman with CED diagnosed in early infancy whose initial complaints included persistent bone pain associated with progressive functional disability. She was treated with steroids but over time became dependent on higher doses with only mild pain relief. In her third decade, she was diagnosed with ulcerative colitis (UC) and was treated with mesalazine, azathioprine and prednisolone. Due to recurrent exacerbations of UC, treatment was changed to infliximab, an antitumour necrosis factor-alpha (TNF?). Remission of UC was achieved and CED-associated pain also improved with infliximab. This is the first report showing a possible role of anti-TNF? in pain management in CED with unsatisfactory response to steroids.
| S-EPMC5720334 | biostudies-literature
Project description:Camurati-Engelmann disease (CED) is a rare sclerosing bone disorder in humans with autosomal dominant inheritance. Mutations in the gene (TGFB1) that encodes transforming growth factor-?1 (TGF-?1) are causative for CED. TGF-?1 signaling is enhanced by the CED-causing mutations. In this study, we performed Tgfb1 mutation screening in an ENU-mutagenized mouse genomic DNA library. We identified a missense mutation in which cysteine was substituted by serine at position 225 (p.C225S), that corresponded to the CED-causing mutation (p.C225R). TGF-?1 mutant protein carrying p.C225S was secreted normally into the extracellular space. Reporter gene assays showed that the p.C225S mutants enhanced TGF-? signaling at the same level as p.C225R mutants. We generated p.C225S homozygous mice and confirmed that the mature TGF-?1 levels in the culture supernatants of the calvarial cells from the homozygotes were significantly higher than those from wild-type mice. Although the skull and femur are sclerotic in CED, these phenotypes were not observed in p.C225S homozygous mice. These results suggest that human and mouse bone tissue react differently to TGF-?1. These findings are useful to pharmacological studies using mouse models in developing drugs that will target TGF-? signaling.
| S-EPMC5411300 | biostudies-literature
Project description:Camurati-Engelmann disease (CED) is a rare autosomal dominant disease with various phenotypic expressions. The hallmark of the disease is bilateral symmetric diaphyseal hyperostosis of the long bones with progressive involvement of the metaphysis. Ocular manifestations occur rarely and mainly result from bony overgrowth of the orbit and optic canal stenosis. We report a case of CED showing angioid streaks (ASs) in both fundi with no macular involvement and discuss the possible theories of the pathogenesis of AS in this disease.
| S-EPMC5549422 | biostudies-other
Project description:Camurati-Engelmann disease is an extremely rare disease characterized by hyperostosis of multiple long bones. This condition is caused by heterozygous mutations in the TGFB1 gene.We describe the clinical and genetic characteristics of 4 Korean patients with this rare disease diagnosed at Asan Medical Center in Korea between June 2012 and May 2016, to increase awareness about this condition among general physicians and orthopedists. The presenting features, biochemical findings, radiographic and nuclear imaging findings, molecular analysis, and treatment outcomes of 4 patients were reviewed retrospectively.Two patients had sporadic disease, whereas the other 2 were familial cases. The average age at symptom onset was 8.8?±?5.5 (4-14) years. Symptoms included waddling gait or leg pain. Bone pain and easy fatigability were documented in all patients. Skeletal deformities such as osteoporosis, genu valgum, and severe scoliosis were observed. Visual and otologic manifestations presenting as exophthalmos, retinal detachment, and vestibulopathy were found in 3 patients. Skeletal survey showed diaphyseal expansion with diffuse cortical thickening of long bones in all patients. Bone scintigraphy images showed increased uptake of radioactive material in the calvarium and diaphysis of long bones. The mean erythrocyte sedimentation rate was 46.5?±?22.2 (20-72)?mm/h. Sequence analysis of TGFB1 revealed the previously reported mutations p.Arg218His, p.Arg218Cys, and p.Glu169Lys. Corticosteroid was effective in relieving pain, and losartan was used as maintenance therapy.Our experience suggests that this rare condition can be suspected in patients with characteristic symptoms and skeletal findings. Considering the presence of effective medical treatment, efforts are needed to identify more cases.
| S-EPMC5902284 | biostudies-literature