Camurati-Engelmann Disease in Conjunction with Hypogonadism

Gupta, Shaili; Cheikh, Issam E.

doi:10.4158/ep.11.6.399

Cited by 16 publications

(15 citation statements)

References 29 publications

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“…Significant endosteal involvement that narrows the medullary cavity in the long bones, may cause hematological complications such as anemia. Delayed puberty and hypogonadism have been reported in some patients [11][12][13].…”

Section: Radiological and Clinical Manifestationsmentioning

confidence: 99%

Camurati–Engelmann Disease

et al. 2019

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Camurati-Engelmann disease or progressive diaphyseal dysplasia is a rare autosomal dominant sclerosing bone dysplasia. Mainly the skull and the diaphyses of the long tubular bones are affected. Clinically, the patients suffer from bone pain, easy fatigability and decreased muscle mass and weakness in the proximal parts of the lower limbs resulting in gait disturbances. The disease causing mutations are located within the TGFβ-1 gene and expected to are thought to disrupt the binding between TGFβ1 and its latency associated peptide resulting in an increased signalling of the pathway and subsequently accelerated bone turnover. In preclinical studies it was shown that targeting the type I receptor ameliorates the high bone turnover. In patients, treatment options are currently mostly limited to corticosteroids that may relieve the pain, improve the muscle weakness and fatigue. In this review the clinical and radiological characteristics as well as the molecular genetics of this condition are discussed.

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Section: Radiological and Clinical Manifestationsmentioning

confidence: 99%

Camurati–Engelmann Disease

et al. 2019

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“…Cranial nerve palsies(12) or raised intracranial pressure can also develop. (13,14) Sometimes puberty is delayed,(13,15) and there may be secondary hypogonadism(16) and prolonged growth. (6) Deafness is not uncommon.…”

Section: Introductionmentioning

confidence: 99%

Camurati-engelmann disease: Unique variant featuring a novel mutation in TGFβ1 encoding transforming growth factor beta 1 and a missense change in TNFSF11 encoding RANK ligand

Whyte

Totty

Novack

et al. 2010

Journal of Bone and Mineral Research

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We report a 32-year-old man and his 59-year-old mother with a unique and extensive variant of Camurati-Engelmann disease (CED) featuring histopathological changes of osteomalacia and alterations within TGFβ1 and TNFSF11 encoding TGFβ1 and RANKL, respectively. He suffered leg pain and weakness since childhood and reportedly grew until his late 20s, reaching 7 feet in height. He had deafness, perforated nasal septum, torus palatinus, disproportionately long limbs with knock-knees, low muscle mass, and pseudoclubbing. Radiographs revealed generalized skeletal abnormalities, including wide bones and cortical and trabecular bone thickening in keeping with CED, except that long bone ends were also affected. Lumbar spine and hip BMD Z-scores were + 7.7 and + 4.4, respectively. Biochemical markers of bone turnover were elevated. Hypocalciuria accompanied low serum 25-hydroxyvitamin D (25[OH]D) levels. Pituitary hypogonadism and low serum insulin-like growth factor (IGF)-1 were present. Karyotype was normal. Despite vitamin D repletion, iliac crest histology revealed severe osteomalacia. Exon 1 of TNFRSF11A (RANK), exons 2, 3, and 4 of LRP5, and all coding exons and adjacent mRNA splice junctions of TNFRSF11B (OPG), SQSTM1 (sequestosome 1), and TNSALP (tissue nonspecific alkaline phosphatase) were intact. His asymptomatic and less dysmorphic 5′11″ mother, also with low serum 25(OH)D, had milder clinical, radiological, biochemical, and histopathological findings. Both individuals were heterozygous for a novel 12-bp duplication (c.27_38dup, p.L10_L13dup) in exon 1 of TGFβ1, predicting four additional leucine residues in the latency-associated-peptide segment of TGFβ1, consistent with CED. The son was also homozygous for a single base transversion in TNFSF11, predicting a nonconservative amino acid change (c.107C > G, p.Pro36Arg) in the intracellular domain of RANKL that was heterozygous in his nonconsanguineous parents. This TNFSF11 variant was not found in the SNP Database, nor in published TNFSF11 association studies, but it occurred in four of the 134 TNFSF11 alleles (3.0%) we tested randomly among individuals without CED. Perhaps the unique phenotype of this CED family is conditioned by altered RANKL activity. © 2011 American Society for Bone and Mineral Research.

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“…Increased bone formation leads to typical hyperostosis in CED. The majority of clinical features are secondary to hyperostosis and sclerosis of the skeleton, including bone pain due to periosteal stretching; skeletal deformities (such as genu valgum and enlarged mandible) due to inappropriately increased bone growth; hearing and/or vision loss, headaches and exophthalmos due to sclerosis of the skull base; and systemic manifestations (such as anemia, leucopenia and hepatosplenomegaly) due to hyperostosis encroaching on marrow cavities, with secondary extramedullary haemopoiesis in the spleen and liver (8,(21)(22)(23). TGFβ1 also has a crucial role in the inhibition of myogenesis (24) and adipogenesis (25), which may explain the reduced subcutaneous fat and easy fatigability associated with CED.…”

Section: Discussionmentioning

confidence: 99%

Mild Camurati-Engelamann disease presenting with exophthalmos as the first and only manifestation: A case report

Jiajue

Jiang

et al. 2016

Molecular Medicine Reports

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Camurati-Engelmann disease (CED; MIM 131300), or progressive diaphyseal dysplasia, is a rare autosomal dominant bone disease, which is caused by mutations in the transforming growth factor‑β1 (TGFβ1) gene on chromosome 19q13.1‑13.3. Extremely variable penetrance has been reported to be associated with CED, the most common features of which are limb pain, waddling gait and muscle weakness. The present study reported on a consanguineous Chinese family with one affected individual that initially presented with exophthalmos, which has not previously been reported as an initial manifestation of CED. The proband was a 22-year-old woman that presented with progressive proptosis. Except for increased serum levels of alkaline phosphatase and C‑terminal telopeptide of type I collagen, no other biochemical abnormalities were detected. Whole‑body radiological and bone scintigraphic investigations revealed that hyperostosis and sclerosis predominantly affected the cranial bones, including the skull base, and only mildly affected the long bones. A heterozygous mutation involving a G to A transition at the cDNA position +653 of TGFβ1 was detected in the patient only, but not in her family members, by automated DNA sequencing using an ABI DNA sequencer (Model 377). Based on the clinical, biochemical, radiological and genetic findings, a diagnosis of CED was confirmed. Considering the phenotypic variability associated with CED and the unique manifestations of the patient described in the present study, CED should be taken into account regarding the differential diagnosis of exophthalmos.

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Camurati-Engelmann Disease in Conjunction with Hypogonadism

Cited by 16 publications

References 29 publications

Camurati–Engelmann Disease

Camurati–Engelmann Disease

Camurati-engelmann disease: Unique variant featuring a novel mutation in TGFβ1 encoding transforming growth factor beta 1 and a missense change in TNFSF11 encoding RANK ligand

Mild Camurati-Engelamann disease presenting with exophthalmos as the first and only manifestation: A case report

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