[[File:Autosomal_recessive_-_en.svg|thumb|right|Diagram of autosomal recessive inheritance]]
| caption = Bruck syndrome is inherited in an autosomal recessive manner
'''Bruck syndrome''' is a rare genetic disorder characterized by a combination of bone fragility and joint contractures. It is classified as a form of [[osteogenesis imperfecta]], which is a group of genetic disorders that primarily affect the bones, making them more prone to fractures. Bruck syndrome is inherited in an [[autosomal recessive]] pattern, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to be affected by the disorder.
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==Clinical Features==
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The primary clinical features of Bruck syndrome include:
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* '''Bone Fragility''': Individuals with Bruck syndrome have bones that are more susceptible to fractures. This is similar to other forms of osteogenesis imperfecta.
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* '''Joint Contractures''': A distinguishing feature of Bruck syndrome is the presence of congenital joint contractures, which are limitations in the range of motion of the joints due to abnormal shortening of the muscles or tendons.
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* '''Short Stature''': Affected individuals often have a shorter stature compared to their peers.
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* '''Skeletal Deformities''': These may include bowing of the long bones, scoliosis, and other deformities due to repeated fractures and abnormal bone healing.
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'''Bruck syndrome''' is characterized as the combination of [[arthrogryposis multiplex congenita]] and [[osteogenesis imperfecta]]. Both diseases are uncommon, but concurrence is extremely rare which makes Bruck syndrome very difficult to research.<ref name="auto">{{Cite journal|title= Bruck syndrome: congenital joint contractures with bone fragility|first1= L.|last1= Mokete|first2= A.|last2= Robertson|first3= D.|last3= Viljoen|first4= Peter|last4= Beighton|journal= Journal of Orthopaedic Science|volume= 10|issue= 6|pages= 641–646|date=2005|doi= 10.1007/s00776-005-0958-9|pmid= 16307191}}</ref> Bruck syndrome is thought to be an atypical variant of osteogenesis imperfecta most resembling type III, if not its own disease.<ref>{{Cite journal|title= Mutations in FKBP10 cause recessive osteogenesis imperfecta and bruck syndrome|first1= C.|last1= Berg|first2= A.|last2= Geipel|first3= F|last3= Noack |display-authors=etal |journal= Prenatal Diagnosis|volume=25|issue= 3|pages=545–548|date=2005|doi= 10.1002/jbmr.250|pmid = 20839288|pmc=3179293}}</ref><ref name="auto1">{{Cite journal|title= Osteogenesis imperfecta with joint contractures: Bruck syndrome|first1= M.|last1= Blacksin|first2= B.|last2= Pletcher|first3= Miriam|last3= David |display-authors=etal |journal= Pediatric Radiology|volume= 28|issue= 2|pages= 117–119|date=1998|doi= 10.1007/s002470050309|pmid = 9472060}}</ref> Multiple gene mutations associated with osteogenesis imperfecta are not seen in Bruck syndrome. Many affected individuals are within the same family, and pedigree data supports that the disease is acquired through autosomal recessive inheritance.<ref name="auto2">{{Cite journal|title= Osteogenesis Imperfecta|first1= V.|last1= Datta|first2= A.|last2= Sinha|first3= A.|last3= Saili |display-authors=etal |journal= Journal of Pediatrics|volume= 72|issue= 5|pages=441–442|date=2005|doi= 10.1007/BF02731745}}</ref> Bruck syndrome has features of [[congenital]] [[contractures]], bone fragility, recurring bone fractures, flexion joint and limb deformities, [[pterygia]], short body height, and progressive [[kyphoscoliosis]]. Individuals encounter restricted mobility and pulmonary function. A reduction in bone mineral content and larger [[hydroxyapatite]] crystals are also detectable<ref>{{Cite journal|pmc=15349|title=Defective collagen crosslinking in bone, but not in ligament or cartilage, in Bruck syndrome: Indications for a bone-specific telopeptide lysyl hydroxylase on chromosome 17|first1= R.|last1= Banks|first2= S.|last2= Robins|last3= Wijmenga |display-authors=etal |journal= Proceedings of the National Academy of Sciences|volume=96|issue=3|pages=1054–1058|year=1999|doi=10.1073/pnas.96.3.1054|pmid=9927692|bibcode=1999PNAS...96.1054B}}</ref> Joint contractures are primarily bilateral and symmetrical, and most prone to ankles.<ref name="auto1"/> Bruck syndrome has no effect on intelligence, vision, or hearing.<ref name="auto2"/>
==Genetics==
==Genetics==
The genetics of Bruck syndrome differs from osteogenesis imperfecta. Osteogenesis imperfecta involves autosomal dominant mutations to Col 1A2 or Col 1A2 which encode type 1 procollagen.<ref name="auto3"/> Bruck syndrome is linked to mutations in two genes, and therefore is divided in two types. Bruck syndrome type 1 is caused by a homozygous mutation in the FKBP10 gene. Type 2 is caused by a homozygous mutation in the PLOD2 gene.<ref name="auto3"/>
Bruck syndrome is caused by mutations in genes that are involved in the formation and maintenance of bone and connective tissue. The two known genes associated with Bruck syndrome are:
==Mechanism==
* '''FKBP10''': Mutations in this gene are responsible for Bruck syndrome type 1.
Type 1 encodes FKBP65, an endoplasmic reticulum associated peptidyl-prolyl cis/trans isomerase ([[Prolyl isomerase|PPIase]]) that functions as a chaperone in collagen biosynthesis. Osteoblasts deficient in FKBP65 have a buildup of procollagen aggregates in the endoplasmic reticulum which reduces their ability to form bone.<ref>{{cite journal|doi=10.1002/ajmg.a.34025|pmid=21567934|pages=1448–1452|date=2011|title=Mutations in FKBP10 cause both Bruck syndrome and isolated osteogenesis imperfecta in humans|journal=American Journal of Medical Genetics Part A|volume=155|issue=6|last1=Shaheen|first1=Ranad|last2=Al-Owain|first2=Mohammed|last3=Faqeih|first3=Eissa|last4=Al-Hashmi|first4=Nadia|last5=Awaji|first5=Ali|last6=Al-Zayed|first6=Zayed|last7=Alkuraya|first7=Fowzan S}}</ref> Furthermore, Bruck syndrome type 1 patients have under-hydroxylated lysine residues in the collagen telopeptide and as a result show diminished hydroxylysylpyridinoline cross-links.<ref name="auto3"/>
* '''PLOD2''': Mutations in this gene cause Bruck syndrome type 2.
Type 2 encodes the enzyme, lysyl hydroxylase 2, which catalyzes hydroxylation of lysine residues in collagen cross-links. PLOD2 is most expressed in active osteoblasts since collagen cross-linking is tissue-specific. Mutation in PLOD2 alters the structure of telopeptide lysyl hydroxylase and prevents fibril formation of collagen type 1. Bone analysis shows the lysine residues of telopeptides in collagen type 1 are under-hydroxylated.<ref name="auto3"/>
Both of these genes play a role in the proper formation of collagen, a key structural protein in bones and connective tissues.
==Diagnosis==
==Diagnosis==
Diagnosis of Bruck syndrome must distinguish the association of contractures and skeletal fragility. Ultrasound is used for prenatal diagnosis. The diagnosis of a neonate bears resemblance to arthrogryposis multiplex congenital, and later in childhood to osteogenesis imperfecta.<ref name="auto"/>
Diagnosis of Bruck syndrome is based on clinical evaluation, family history, and genetic testing. Radiographic imaging can reveal characteristic bone abnormalities, while genetic testing can confirm mutations in the FKBP10 or PLOD2 genes.
==Management==
==Management==
Until more molecular and clinical studies are performed there will be no way to prevent the disease. Treatments are directed towards alleviating the symptoms. To treat the disease it is crucial to diagnose it properly.<ref name="auto3">{{Cite journal|title= Bruck syndrome: osteogenesis imperfecta and arthrogryposis multiplex congenital|first1= H.|last1= Yapicioglu |first2= K.|last2= Ozcan |first3=O.|last3= Arikan |display-authors=etal |journal= Annals of Tropical Paediatrics|volume=29|issue= 2|pages=159–1662|date=2009|doi=10.1179/146532809x440798|pmid= 19460271}}</ref> Orthopedic therapy and fracture management are necessary to reduce the severity of symptoms. Bisphosphonate drugs are also an effective treatment.<ref name="auto2"/>
There is currently no cure for Bruck syndrome, and management focuses on preventing fractures, maintaining mobility, and addressing any complications. Treatment strategies may include:
==History==
The first case was in 1897 of a male who was described by Bruck as having bone fragility and bone contractures.<ref name="auto2"/> Bruck was credited with the first description and the disease’s eponym.<ref name="auto"/>
==References==
* '''Physical Therapy''': To improve joint mobility and muscle strength.
{{reflist}}
* '''Orthopedic Interventions''': Such as bracing or surgery to correct bone deformities and stabilize joints.
* '''Bisphosphonates''': Medications that can help increase bone density and reduce fracture risk.
==Further reading==
==Prognosis==
*{{cite journal | last1 = Breslau-Siderius | first1 = E. J. |display-authors=et al | year = 1998 | title = Brack syndrome: a rare combination of bone fragility and multiple congenital joint contractures | url = | journal = Journal of Pediatric Orthopaedics B | volume = 7 | issue = 1| pages = 35–38 | doi=10.1097/01202412-199801000-00006}}
The prognosis for individuals with Bruck syndrome varies depending on the severity of the condition. With appropriate management, many individuals can lead active lives, although they may require ongoing medical care and support.
== External links ==
==Related pages==
{{Medical resources
* [[Osteogenesis imperfecta]]
| ICD10 = M21.8
* [[Genetic disorders]]
| ICD9 = <!--{{ICD9|xxx}}-->
* [[Connective tissue disease]]
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| OMIM = 259450
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| Orphanet = 2771
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[[Category:Genetic diseases and disorders]]
[[Category:Genetic disorders]]
[[Category:Abnormalities of dermal fibrous and elastic tissue]]
[[Category:Rare diseases]]
[[Category:Skeletal disorders]]
[[Category:Connective tissue diseases]]
[[Category:Rare syndromes]]
[[Category:Syndromes affecting bones]]
[[Category:Syndromes affecting joints]]
[[Category:Syndromes affecting stature]]
{{dictionary-stub1}}
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Revision as of 05:56, 16 February 2025
A rare genetic disorder affecting bone development
Bruck syndrome is a rare genetic disorder characterized by a combination of bone fragility and joint contractures. It is classified as a form of osteogenesis imperfecta, which is a group of genetic disorders that primarily affect the bones, making them more prone to fractures. Bruck syndrome is inherited in an autosomal recessive pattern, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to be affected by the disorder.
Clinical Features
The primary clinical features of Bruck syndrome include:
Bone Fragility: Individuals with Bruck syndrome have bones that are more susceptible to fractures. This is similar to other forms of osteogenesis imperfecta.
Joint Contractures: A distinguishing feature of Bruck syndrome is the presence of congenital joint contractures, which are limitations in the range of motion of the joints due to abnormal shortening of the muscles or tendons.
Short Stature: Affected individuals often have a shorter stature compared to their peers.
Skeletal Deformities: These may include bowing of the long bones, scoliosis, and other deformities due to repeated fractures and abnormal bone healing.
Genetics
Bruck syndrome is caused by mutations in genes that are involved in the formation and maintenance of bone and connective tissue. The two known genes associated with Bruck syndrome are:
FKBP10: Mutations in this gene are responsible for Bruck syndrome type 1.
PLOD2: Mutations in this gene cause Bruck syndrome type 2.
Both of these genes play a role in the proper formation of collagen, a key structural protein in bones and connective tissues.
Diagnosis
Diagnosis of Bruck syndrome is based on clinical evaluation, family history, and genetic testing. Radiographic imaging can reveal characteristic bone abnormalities, while genetic testing can confirm mutations in the FKBP10 or PLOD2 genes.
Management
There is currently no cure for Bruck syndrome, and management focuses on preventing fractures, maintaining mobility, and addressing any complications. Treatment strategies may include:
Physical Therapy: To improve joint mobility and muscle strength.
Orthopedic Interventions: Such as bracing or surgery to correct bone deformities and stabilize joints.
Bisphosphonates: Medications that can help increase bone density and reduce fracture risk.
Prognosis
The prognosis for individuals with Bruck syndrome varies depending on the severity of the condition. With appropriate management, many individuals can lead active lives, although they may require ongoing medical care and support.
