RARE DISEASE
Camurati-Engelmann disease
Camurati-Engelmann disease
Camurati-Engelmann disease
Synonyms: Progressive diaphyseal dysplasia
Synonyms: Progressive diaphyseal dysplasia
Synonyms: Progressive diaphyseal dysplasia
Drug discovery
1
drug
With orphan designation
Overview
Camurati-Engelmann disease (CED) is a rare autosomal dominant skeletal dysplasia caused by TGFB1 gene mutations, leading to progressive hyperostosis of long bones, skull, and pelvis. Clinically, it manifests with limb pain, muscle weakness, waddling gait, and potential cranial nerve compression causing vision/hearing loss. Symptom onset typically occurs before age 30, with variable penetrance. Management includes corticosteroids for symptom relief, losartan for TGFβ-1 inhibition, and physical therapy, though no curative therapies exist [1][3][9][10][17].
Categories: rare bone diseases, rare developmental anomalies during embryogenesis, rare genetic diseases
Research Papers
84 drug discovery papers about Camurati-Engelmann disease, with 1 first-in-class and 5 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
84 drug discovery papers about Camurati-Engelmann disease, with 1 first-in-class and 5 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-06-17 | Camurati-Engelmann Disease: A Narrative Review of Clinical Features, Molecular Pathogenesis, Diagnosis, and Emerging Targeted Therapies
Camurati-Engelmann Disease (CED) is a very rare, autosomal-dominant type sclerosing bone dysplasia that is characterised by progressive diaphyseal hyperostosis, cortical thickening of long bones, along with variable involvement of skull-base. This narrative review synthesises the current evidence regarding clinical features, molecular basis, diagnosis, as well as management strategies of CED. Clinically, patients having CED, usually present in childhood or adolescence age with chronic pain in limbs, proximal muscle weakness, fatigability, along with a waddling gait, while cranial hyperostosis may lead to hearing impairment, cranial nerve deficits, or raised intracranial pressure. Pathogenic heterozygous mutations in Transforming Growth Factor Beta 1 (TGFB1), also less commonly Transforming Growth Factor Beta 1 (TGFB2), can cause disruption of the latency-associated peptide domain of TGF-β, which can result in excessive TGF-β activation along with downstream dysregulation of bone remodeling pathways. Diagnosis of CED primarily depends upon identification of typical clinical features, characteristic imaging findings of symmetric diaphyseal sclerosis, also definitive confirmation although is done using genetic testing. Management of CED is usually symptomatic, which is inclusive of analgesics, glucocorticoids, and emerging usage of angiotensin II receptor blockers such as losartan. Surgical decompression is usually reserved only for few cases which present with skull-base complications. Novel therapeutic strategies that target TGF-β axis, including receptor inhibitors, ligand traps, as well as Rho-GTPase pathway modulators, also represent promising options as disease-modifying treatment. Improved understanding of various molecular mechanisms for CED along with long-term clinical outcomes is essential for enhancing patient care and quality of life. This narrative review article focuses on uniquely merging updated molecular insights on dysregulated TGF-β signalling along with contemporary diagnostic algorithms, emerging targeted therapies, thus providing a consolidated, clinically oriented framework which is currently lacking in existing literature about CED.
2026-04-08 | Camurati-Engelmann disease with bilateral proptosis and optic neuropathy: a case report and literature review.
Camurati-Engelmann disease (CED) is a rare autosomal dominant skeletal disorder caused by mutations in the TGFB1 gene and is characterized by progressive diaphyseal widening and cortical thickening of long bones. A 29-year-old woman presented with bilateral proptosis, hypothyroidism and a 15-year history of hearing loss and limb pain. Superior visual field defects were detected on automated perimetry. Orbital computed tomography demonstrated orbital apex crowding and narrowing of the optic canals caused by skull hyperostosis, raising concern for compressive optic neuropathy. Imaging revealed systemic skeletal abnormalities, including macrocephaly, mandibular overgrowth, and cortical thickening of multiple bones. Genetic testing confirmed a pathogenic TGFB1 mutation, establishing the diagnosis of CED. Treatment with zoledronic acid, methotrexate, and hormone replacement therapy improved bone metabolism and relieved bone pain at the six-month follow-up. At one-year follow-up, optical coherence tomography showed reduced peripapillary retinal nerve fiber layer thickness (mean 66 μm in both eyes), accompanied by mild progression of visual field defects. Orbital apex decompression with possible optic canal decompression was considered if visual function declined further. This case highlights the potential for orbital involvement and compressive optic neuropathy in CED and underscores the importance of multidisciplinary management and regular ophthalmologic monitoring.
2025-08-13 | Identification of a novel TGFB1 variant in a patient with Camurati-Engelmann disease responsive to alendronate
Whole genome sequencing and alendronate may be of value in diagnosing and managing CED, respectively.
2025-04-10 | Transforming growth factor, beta-2 gene mutation causes autosomal dominant Camurati-Engelmann disease, type 2 (OMIM % 606631).
Camurati-Engelmann disease, type 1 (CED1, OMIM # 131300) is the rare autosomal dominant skeletal dysplasia caused by select heterozygous loss-of-function defects within the gene TGFB1, which encodes transforming growth factor beta 1 (TGFB1). CED1 mutations are found in TGFB1 exons 1-4 that form the latency-associated peptide (LAP) of pro-TGFB1. Consequently, skeletal action of TGFB1 increases and thereby enhances bone formation manifest clinically as "progressive diaphyseal dysplasia". Beginning 24 years ago negative TGFB1 analysis suggested rare genetic heterogeneity for CED, and Online Mendelian Inheritance In Man designated, of unknown etiology, "CED2" (OMIM % 606631). In 2024, three sporadic occurrences considered CED2 were reported to harbor either of two mutations of TGFB2, which encodes the LAP of transforming growth factor beta 2 (TGFB2). Herein, three adults (father, son, daughter) having the CED2 phenotype in a Peruvian family revealed a novel missense variant (c.108G > T, p.R36S) within the TGFB2 LAP domain. Debilitating painful skeletal disease featuring hyperostosis of entire long bones, worse in the men, presented early in childhood. Aminobisphosphonate therapy seemed helpful. Their TGFB2 variant was within a highly conserved domain across species, absent in the gnomAD database, "possibly damaging" by Polyphen-2, not tolerated by SIFT, homologous with TGFB1 at the same amino acid position (R36) as one reported TGFB2 mutation, co-segregated as autosomal dominant, and "likely pathogenic" per ACMG guidelines.
2025-03-17 | P454: Improvement in refractory bone pain with infliximab in an adolescent with Camurati-Engelmann disease
Diagnostic Workup: Brain MRI identified significant cortical dysplasia and cortical thickening with absence of normal sulcation of left hemisphere.EEG revealed status epilepticus on multiple occasions.Biochemical labs included plasma amino acids, urine organic acids, and an acylcarnitine profile.All were non-diagnostic.Newborn screening #1 was normal, though #2 was positive for congenital adrenal hyperplasia and congenital hypothyroidism.Genetic testing included a rapid proband-only genome sequence analysis.Positive results include a pathogenic variant in PTEN (c.388C>T), a likely pathogenic variant in WDR19 (c.3652dup) and 2 VUS in WDR19 (c.2365G>A and c.2671C>T).Secondary findings were declined by the family.
2026-06-17 | Camurati-Engelmann Disease: A Narrative Review of Clinical Features, Molecular Pathogenesis, Diagnosis, and Emerging Targeted Therapies
Camurati-Engelmann Disease (CED) is a very rare, autosomal-dominant type sclerosing bone dysplasia that is characterised by progressive diaphyseal hyperostosis, cortical thickening of long bones, along with variable involvement of skull-base. This narrative review synthesises the current evidence regarding clinical features, molecular basis, diagnosis, as well as management strategies of CED. Clinically, patients having CED, usually present in childhood or adolescence age with chronic pain in limbs, proximal muscle weakness, fatigability, along with a waddling gait, while cranial hyperostosis may lead to hearing impairment, cranial nerve deficits, or raised intracranial pressure. Pathogenic heterozygous mutations in Transforming Growth Factor Beta 1 (TGFB1), also less commonly Transforming Growth Factor Beta 1 (TGFB2), can cause disruption of the latency-associated peptide domain of TGF-β, which can result in excessive TGF-β activation along with downstream dysregulation of bone remodeling pathways. Diagnosis of CED primarily depends upon identification of typical clinical features, characteristic imaging findings of symmetric diaphyseal sclerosis, also definitive confirmation although is done using genetic testing. Management of CED is usually symptomatic, which is inclusive of analgesics, glucocorticoids, and emerging usage of angiotensin II receptor blockers such as losartan. Surgical decompression is usually reserved only for few cases which present with skull-base complications. Novel therapeutic strategies that target TGF-β axis, including receptor inhibitors, ligand traps, as well as Rho-GTPase pathway modulators, also represent promising options as disease-modifying treatment. Improved understanding of various molecular mechanisms for CED along with long-term clinical outcomes is essential for enhancing patient care and quality of life. This narrative review article focuses on uniquely merging updated molecular insights on dysregulated TGF-β signalling along with contemporary diagnostic algorithms, emerging targeted therapies, thus providing a consolidated, clinically oriented framework which is currently lacking in existing literature about CED.
2026-04-08 | Camurati-Engelmann disease with bilateral proptosis and optic neuropathy: a case report and literature review.
Camurati-Engelmann disease (CED) is a rare autosomal dominant skeletal disorder caused by mutations in the TGFB1 gene and is characterized by progressive diaphyseal widening and cortical thickening of long bones. A 29-year-old woman presented with bilateral proptosis, hypothyroidism and a 15-year history of hearing loss and limb pain. Superior visual field defects were detected on automated perimetry. Orbital computed tomography demonstrated orbital apex crowding and narrowing of the optic canals caused by skull hyperostosis, raising concern for compressive optic neuropathy. Imaging revealed systemic skeletal abnormalities, including macrocephaly, mandibular overgrowth, and cortical thickening of multiple bones. Genetic testing confirmed a pathogenic TGFB1 mutation, establishing the diagnosis of CED. Treatment with zoledronic acid, methotrexate, and hormone replacement therapy improved bone metabolism and relieved bone pain at the six-month follow-up. At one-year follow-up, optical coherence tomography showed reduced peripapillary retinal nerve fiber layer thickness (mean 66 μm in both eyes), accompanied by mild progression of visual field defects. Orbital apex decompression with possible optic canal decompression was considered if visual function declined further. This case highlights the potential for orbital involvement and compressive optic neuropathy in CED and underscores the importance of multidisciplinary management and regular ophthalmologic monitoring.
2025-08-13 | Identification of a novel TGFB1 variant in a patient with Camurati-Engelmann disease responsive to alendronate
Whole genome sequencing and alendronate may be of value in diagnosing and managing CED, respectively.
2025-04-10 | Transforming growth factor, beta-2 gene mutation causes autosomal dominant Camurati-Engelmann disease, type 2 (OMIM % 606631).
Camurati-Engelmann disease, type 1 (CED1, OMIM # 131300) is the rare autosomal dominant skeletal dysplasia caused by select heterozygous loss-of-function defects within the gene TGFB1, which encodes transforming growth factor beta 1 (TGFB1). CED1 mutations are found in TGFB1 exons 1-4 that form the latency-associated peptide (LAP) of pro-TGFB1. Consequently, skeletal action of TGFB1 increases and thereby enhances bone formation manifest clinically as "progressive diaphyseal dysplasia". Beginning 24 years ago negative TGFB1 analysis suggested rare genetic heterogeneity for CED, and Online Mendelian Inheritance In Man designated, of unknown etiology, "CED2" (OMIM % 606631). In 2024, three sporadic occurrences considered CED2 were reported to harbor either of two mutations of TGFB2, which encodes the LAP of transforming growth factor beta 2 (TGFB2). Herein, three adults (father, son, daughter) having the CED2 phenotype in a Peruvian family revealed a novel missense variant (c.108G > T, p.R36S) within the TGFB2 LAP domain. Debilitating painful skeletal disease featuring hyperostosis of entire long bones, worse in the men, presented early in childhood. Aminobisphosphonate therapy seemed helpful. Their TGFB2 variant was within a highly conserved domain across species, absent in the gnomAD database, "possibly damaging" by Polyphen-2, not tolerated by SIFT, homologous with TGFB1 at the same amino acid position (R36) as one reported TGFB2 mutation, co-segregated as autosomal dominant, and "likely pathogenic" per ACMG guidelines.
2025-03-17 | P454: Improvement in refractory bone pain with infliximab in an adolescent with Camurati-Engelmann disease
Diagnostic Workup: Brain MRI identified significant cortical dysplasia and cortical thickening with absence of normal sulcation of left hemisphere.EEG revealed status epilepticus on multiple occasions.Biochemical labs included plasma amino acids, urine organic acids, and an acylcarnitine profile.All were non-diagnostic.Newborn screening #1 was normal, though #2 was positive for congenital adrenal hyperplasia and congenital hypothyroidism.Genetic testing included a rapid proband-only genome sequence analysis.Positive results include a pathogenic variant in PTEN (c.388C>T), a likely pathogenic variant in WDR19 (c.3652dup) and 2 VUS in WDR19 (c.2365G>A and c.2671C>T).Secondary findings were declined by the family.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
1 orphan drug designation for Camurati-Engelmann disease.
1 orphan drug designation for Camurati-Engelmann disease.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Sodium (1-hydroxy-4-(((2-((4-(2-(pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)quinolin-7-yl)oxy)ethoxy)carbonyl)amino)butane-1,1-diyl)bis(hydrogen phosphonate) | small molecules | FDA | 2022-09-01 | — | Brise Pharmaceuticals Co., Ltd. |
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