BRKS1
MCID: BRC047
MIFTS: 32

Bruck Syndrome 1 (BRKS1)

Categories: Bone diseases, Fetal diseases, Genetic diseases, Oral diseases, Rare diseases

Aliases & Classifications for Bruck Syndrome 1

MalaCards integrated aliases for Bruck Syndrome 1:

Name: Bruck Syndrome 1 56 52 25 73 29 13 6 71
Kuskokwim Disease 56 74 52 25 58 73 71
Kuskokwim Syndrome 52 25 58 71
Arthrogryposis-Like Disorder 56 52 73
Arthrogryposis-Like Syndrome 52 25 58
Brks1 56 52 73
Osteogenesis Imperfecta with Congenital Joint Contractures 52
Arthrogryposis Like Disorder 74
Syndrome, Bruck, Type 1 39
Bruck Syndrome-1 52

Characteristics:

Orphanet epidemiological data:

58
kuskokwim syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood,Neonatal;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
onset of fractures in infancy to early childhood


HPO:

31
bruck syndrome 1:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Developmental anomalies during embryogenesis


Summaries for Bruck Syndrome 1

Genetics Home Reference : 25 Kuskokwim syndrome is characterized by joint deformities called contractures that restrict the movement of affected joints. This condition has been found only in a population of native Alaskans known as Yup'ik Eskimos, who live in and around a region of southwest Alaska known as the Kuskokwim River Delta. In Kuskokwim syndrome, contractures most commonly affect the knees, ankles, and elbows, although other joints, particularly of the lower body, can be affected. The contractures are usually present at birth and worsen during childhood. They tend to stabilize after childhood, and they remain throughout life. Some individuals with this condition have other bone abnormalities, most commonly affecting the spine, pelvis, and feet. Affected individuals can develop an inward curve of the lower back (lordosis), a spine that curves to the side (scoliosis), wedge-shaped spinal bones, or an abnormality of the collarbones (clavicles) described as clubbing. Affected individuals are typically shorter than their peers and they may have an abnormally large head (macrocephaly).

MalaCards based summary : Bruck Syndrome 1, also known as kuskokwim disease, is related to bruck syndrome 2 and bruck syndrome. An important gene associated with Bruck Syndrome 1 is FKBP10 (FKBP Prolyl Isomerase 10). Affiliated tissues include bone, and related phenotypes are joint stiffness and gait disturbance

NIH Rare Diseases : 52 The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 2771 Definition Bruck syndrome is characterised by the association of osteogenesis imperfecta and congenital joint contractures . Epidemiology Prevalence is unknown but less than 40 cases have been reported in the literature so far. Clinical description Features include osteoporosis and bone fragility, progressive joint contractures sometimes associated with pterygia, wormian bones, scoliosis due to vertebral deformities and short stature . Mental development is normal. Etiology The syndrome is genetically heterogeneous: the locus was mapped to chromosome 17p12 in one family (Bruck syndrome 1) but mutations in the PLOD2 gene (3q24) encoding telopeptide lysyl hydroxylase (Bruck syndrome 2) have been identified in other affected individuals. Genetic counseling Transmission is autosomal recessive . Visit the Orphanet disease page for more resources.

OMIM : 56 Bruck syndrome is characterized by congenital contractures with pterygia, onset of fractures in infancy or early childhood, postnatal short stature, severe limb deformity, and progressive scoliosis (McPherson and Clemens, 1997). (259450)

UniProtKB/Swiss-Prot : 73 Bruck syndrome 1: A disease characterized by generalized osteopenia, congenital joint contractures, fragile bones with onset of fractures in infancy or early childhood, short stature, severe limb deformity, progressive scoliosis, and pterygia.

Wikipedia : 74 Arthrogryposis multiplex congenita (AMC), or simply arthrogryposis, describes congenital joint... more...

Related Diseases for Bruck Syndrome 1

Diseases in the Bruck Syndrome family:

Bruck Syndrome 1 Bruck Syndrome 2

Diseases related to Bruck Syndrome 1 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 bruck syndrome 2 11.8
2 bruck syndrome 11.3
3 brittle bone disorder 10.5
4 dentinogenesis imperfecta 10.4
5 torticollis 10.2
6 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.2
7 scoliosis 10.2
8 congenital contractures 10.2
9 alkuraya-kucinskas syndrome 10.1
10 congenital amyoplasia 10.1

Graphical network of the top 20 diseases related to Bruck Syndrome 1:



Diseases related to Bruck Syndrome 1

Symptoms & Phenotypes for Bruck Syndrome 1

Human phenotypes related to Bruck Syndrome 1:

58 31 (show all 26)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 joint stiffness 58 31 hallmark (90%) Very frequent (99-80%) HP:0001387
2 gait disturbance 58 31 hallmark (90%) Very frequent (99-80%) HP:0001288
3 aplasia/hypoplasia of the patella 58 31 hallmark (90%) Very frequent (99-80%) HP:0006498
4 talipes 58 31 frequent (33%) Frequent (79-30%) HP:0001883
5 scoliosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002650
6 abnormal form of the vertebral bodies 58 31 occasional (7.5%) Occasional (29-5%) HP:0003312
7 melanocytic nevus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000995
8 reduced tendon reflexes 58 31 occasional (7.5%) Occasional (29-5%) HP:0001315
9 abnormality of the clavicle 58 31 occasional (7.5%) Occasional (29-5%) HP:0000889
10 aplasia/hypoplasia of the radius 58 31 occasional (7.5%) Occasional (29-5%) HP:0006501
11 kyphosis 31 HP:0002808
12 pectus carinatum 31 HP:0000768
13 short stature 31 HP:0004322
14 osteoporosis 31 HP:0000939
15 elbow flexion contracture 31 HP:0002987
16 joint laxity 31 HP:0001388
17 talipes equinovarus 31 HP:0001762
18 protrusio acetabuli 31 HP:0003179
19 platyspondyly 31 HP:0000926
20 coxa vara 31 HP:0002812
21 hip contracture 31 HP:0003273
22 vertebral wedging 31 HP:0008422
23 pterygium 31 HP:0001059
24 ankle flexion contracture 31 HP:0006466
25 knee flexion contracture 31 HP:0006380
26 increased susceptibility to fractures 31 HP:0002659

Symptoms via clinical synopsis from OMIM:

56
Skeletal Spine:
scoliosis
kyphosis
vertebral wedging
flattened vertebral bodies

Growth Height:
short stature

Skeletal Feet:
talipes equinovarus

Head And Neck Teeth:
normal teeth

Head And Neck Eyes:
normal sclerae

Chest Ribs Sternum Clavicles And Scapulae:
pectus carinatum

Skeletal:
osteoporosis
bone fragility
joint contractures, congenital (knee, ankle, hip, elbow)
joint laxity (fingers and wrist)

Skeletal Pelvis:
protrusio acetabuli
coxa vara

Head And Neck Ears:
normal hearing

Skin Nails Hair Skin:
pterygia (knees and elbows)

Clinical features from OMIM:

259450

Drugs & Therapeutics for Bruck Syndrome 1

Search Clinical Trials , NIH Clinical Center for Bruck Syndrome 1

Genetic Tests for Bruck Syndrome 1

Genetic tests related to Bruck Syndrome 1:

# Genetic test Affiliating Genes
1 Bruck Syndrome 1 29 FKBP10

Anatomical Context for Bruck Syndrome 1

MalaCards organs/tissues related to Bruck Syndrome 1:

40
Bone

Publications for Bruck Syndrome 1

Articles related to Bruck Syndrome 1:

(show all 16)
# Title Authors PMID Year
1
Kuskokwim syndrome, a recessive congenital contracture disorder, extends the phenotype of FKBP10 mutations. 6 56
23712425 2013
2
Mutations in PLOD2 cause autosomal-recessive connective tissue disorders within the Bruck syndrome--osteogenesis imperfecta phenotypic spectrum. 56 6
22689593 2012
3
Mutations in FKBP10 cause both Bruck syndrome and isolated osteogenesis imperfecta in humans. 56 6
21567934 2011
4
Mutations in FKBP10 cause recessive osteogenesis imperfecta and Bruck syndrome. 56 6
20839288 2011
5
FKBP10 and Bruck syndrome: phenotypic heterogeneity or call for reclassification? 6 56
20696291 2010
6
Mutations in the gene encoding the RER protein FKBP65 cause autosomal-recessive osteogenesis imperfecta. 6 56
20362275 2010
7
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. 6 56
9927692 1999
8
Bruck syndrome (osteogenesis imperfecta with congenital joint contractures): review and report on the first North American case. 6 56
9129737 1997
9
Arthrogryposis syndrome (Kuskokwim disease) in the Eskimo. 56 61
4241085 1969
10
Mutations in FKBP10, which result in Bruck syndrome and recessive forms of osteogenesis imperfecta, inhibit the hydroxylation of telopeptide lysines in bone collagen. 6
22949511 2013
11
Absence of FKBP10 in recessive type XI osteogenesis imperfecta leads to diminished collagen cross-linking and reduced collagen deposition in extracellular matrix. 6
22718341 2012
12
Phenotypic and molecular characterization of Bruck syndrome (osteogenesis imperfecta with contractures of the large joints) caused by a recessive mutation in PLOD2. 56
15523624 2004
13
Identification of PLOD2 as telopeptide lysyl hydroxylase, an important enzyme in fibrosis. 56
12881513 2003
14
Bruck syndrome: a rare combination of bone fragility and multiple congenital joint contractures. 6
9481655 1998
15
Defective collagen fibril formation and mineralization in osteogenesis imperfecta with congenital joint contractures (Bruck syndrome). 56
8335019 1993
16
Osteogenesis imperfecta with congenital joint contractures (Bruck syndrome). 56
2766569 1989

Variations for Bruck Syndrome 1

ClinVar genetic disease variations for Bruck Syndrome 1:

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 FKBP10 NM_021939.3(FKBP10):c.1276dup (p.Gln426fs)duplication Pathogenic 30633 rs1567856056 17:39977212-39977213 17:41820960-41820961
2 FKBP10 NM_021939.3(FKBP10):c.1271_1272delinsA (p.Ala424fs)indel Pathogenic 41425 rs397509383 17:39977213-39977214 17:41820961-41820962
3 FKBP10 FKBP10, 8-BP DUP, NT1016duplication Pathogenic 30631
4 FKBP10 NM_021939.3(FKBP10):c.344G>A (p.Arg115Gln)SNV Pathogenic 30634 rs387906960 17:39973408-39973408 17:41817156-41817156
5 FKBP10 NM_021939.3(FKBP10):c.743dup (p.Gln249fs)duplication Pathogenic 30635 rs1555616552 17:39975471-39975472 17:41819219-41819220
6 FKBP10 NM_021939.3(FKBP10):c.337G>A (p.Glu113Lys)SNV Pathogenic 41473 rs397514674 17:39973401-39973401 17:41817149-41817149
7 FKBP10 NM_021939.3(FKBP10):c.831dup (p.Gly278fs)duplication Pathogenic 438659 rs137853883 17:39975558-39975559 17:41819306-41819307
8 FKBP10 NM_021939.3(FKBP10):c.877_879del (p.Tyr293del)deletion Pathogenic 208427 rs869320752 17:39975609-39975611 17:41819357-41819359
9 FKBP10 NM_021939.3(FKBP10):c.890_897dup (p.Gly300Ter)duplication Pathogenic/Likely pathogenic 631496 rs1567855132 17:39975623-39975624 17:41819371-41819372
10 FKBP10 NM_021939.3(FKBP10):c.1667G>A (p.Arg556His)SNV Uncertain significance 193735 rs138281924 17:39978578-39978578 17:41822326-41822326

UniProtKB/Swiss-Prot genetic disease variations for Bruck Syndrome 1:

73
# Symbol AA change Variation ID SNP ID
1 FKBP10 p.Glu113Lys VAR_069902 rs397514674
2 FKBP10 p.Arg115Gln VAR_069903 rs387906960
3 FKBP10 p.Pro136Leu VAR_069904 rs782653042

Expression for Bruck Syndrome 1

Search GEO for disease gene expression data for Bruck Syndrome 1.

Pathways for Bruck Syndrome 1

GO Terms for Bruck Syndrome 1

Sources for Bruck Syndrome 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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