MCID: LRS001
MIFTS: 47

Larsen Syndrome

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

Aliases & Classifications for Larsen Syndrome

MalaCards integrated aliases for Larsen Syndrome:

Name: Larsen Syndrome 53 12 72 49 24 71 28 13 14 69
Lrs 53 49 24 71
Larsen Syndrome, Dominant Type 72 28 69
Autosomal Dominant Larsen Syndrome 49 55
Dominant Larsen Syndrome 12
Joint Dislocations 41
Joint Dislocation 28
Larsens Syndrome 51

Characteristics:

Orphanet epidemiological data:

55
autosomal dominant larsen syndrome
Inheritance: Autosomal dominant; Prevalence: 1-9/1000000 (Europe); Age of onset: Infancy,Neonatal; Age of death: normal life expectancy;

OMIM:

53
Inheritance:
autosomal dominant

Miscellaneous:
intrafamilial variation
autosomal recessive inheritance has also been suggested
joint dislocations become less frequent with age


HPO:

31
larsen syndrome:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Larsen Syndrome

OMIM : 53 Larsen syndrome is an osteochondrodysplasia characterized by large-joint dislocations and characteristic craniofacial abnormalities. The cardinal features of the condition are dislocations of the hip, knee and elbow joints, with equinovarus or equinovalgus foot deformities. Spatula-shaped fingers, most marked in the thumb, are also present. Craniofacial anomalies include hypertelorism, prominence of the forehead, a depressed nasal bridge, and a flattened midface. Cleft palate and short stature are often associated features. Spinal anomalies include scoliosis and cervical kyphosis. Hearing loss is a well-recognized complication (summary by Bicknell et al., 2007). (150250)

MalaCards based summary : Larsen Syndrome, also known as lrs, is related to reunion island larsen syndrome and spondyloepiphyseal dysplasia with congenital joint dislocations, and has symptoms including malar flattening, hypertelorism and abnormality of epiphysis morphology. An important gene associated with Larsen Syndrome is FLNB (Filamin B), and among its related pathways/superpathways is Chondroitin sulfate/dermatan sulfate metabolism. Affiliated tissues include bone, spinal cord and brain, and related phenotypes are Increased shRNA abundance (Z-score > 2) and Increased shRNA abundance (Z-score > 2)

UniProtKB/Swiss-Prot : 71 Larsen syndrome: An osteochondrodysplasia characterized by large-joint dislocations and characteristic craniofacial abnormalities. The cardinal features of the condition are dislocations of the hip, knee and elbow joints, with equinovarus or equinovalgus foot deformities. Spatula-shaped fingers, most marked in the thumb, are also present. Craniofacial anomalies include hypertelorism, prominence of the forehead, a depressed nasal bridge, and a flattened midface. Cleft palate and short stature are often associated features. Spinal anomalies include scoliosis and cervical kyphosis. Hearing loss is a well-recognized complication.

NIH Rare Diseases : 49 Larsen syndrome is a condition that causes abnormal development of the bones. Signs and symptoms may include clubfoot and numerous joint dislocations at birth (affecting the hips, knees and elbows); flexible joints; and a distinctive appearance of the face, hands and feet. Larsen syndrome is inherited in an autosomal dominant manner and is caused by mutations in the FLNB gene. Management may include surgeries (especially for hip dislocation), and physiotherapy. Last updated: 3/31/2014

Genetics Home Reference : 24 Larsen syndrome is a disorder that affects the development of bones throughout the body. The signs and symptoms of Larsen syndrome vary widely even within the same family. Affected individuals are usually born with inward- and upward-turning feet (clubfeet) and dislocations of the hips, knees, and elbows. They generally have small extra bones in their wrists and ankles that are visible on x-ray images. The tips of their fingers, especially the thumbs, are typically blunt and square-shaped (spatulate).

Disease Ontology : 12 An autosomal dominant disease that is characterized by large-joint dislocations and characteristic craniofacial abnormalities.

Wikipedia : 72 Larsen syndrome (LS) is a congenital disorder discovered in 1950 by Larsen and associates when they... more...

Related Diseases for Larsen Syndrome

Diseases in the Larsen Syndrome family:

Larsen-Like Syndrome

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

(show all 42)
# Related Disease Score Top Affiliating Genes
1 reunion island larsen syndrome 11.9
2 spondyloepiphyseal dysplasia with congenital joint dislocations 11.6
3 multiple joint dislocations, short stature, and craniofacial dysmorphism with or without congenital heart defects 11.4
4 desbuquois dysplasia 1 11.3
5 duane retraction syndrome 3 with or without deafness 11.1
6 atelosteogenesis, type iii 10.9
7 bone dysplasia, lethal, holmgren type 10.9
8 cervicitis 10.2
9 pyruvate kinase deficiency of red cells 10.1
10 malignant hyperthermia 10.0
11 aging 9.9
12 hepatitis 9.9
13 scrapie 9.9
14 arthrogryposis multiplex congenita, neurogenic, with myelin defect 9.9
15 creutzfeldt-jakob disease 9.7
16 cholangiocarcinoma 9.7
17 diabetes mellitus 9.7
18 hemolytic anemia 9.7
19 insulinoma 9.7
20 spondylosis 9.7
21 colon adenocarcinoma 9.7
22 adenocarcinoma 9.7
23 astrocytoma 9.7
24 ischemia 9.7
25 peritonitis 9.7
26 encephalopathy 9.7
27 bronchomalacia 9.7
28 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 9.7
29 craniosynostosis 9.7
30 hydrocephalus 9.7
31 scoliosis 9.7
32 tracheomalacia 9.7
33 cardiac arrest 9.7
34 oligohydramnios 9.7
35 quadriplegia 9.7
36 dysostosis 9.7
37 mediastinitis 9.7
38 dwarfism 9.7
39 skeletal dysplasias 9.7
40 aneurysm 9.7
41 trisomy 1q 9.7
42 congenital knee dislocation 9.7

Graphical network of the top 20 diseases related to Larsen Syndrome:



Diseases related to Larsen Syndrome

Symptoms & Phenotypes for Larsen Syndrome

Symptoms via clinical synopsis from OMIM:

53
SkeletalLimbs:
joint laxity
dislocations of the elbows
dislocations of the wrists
dislocations of the knees
dysplastic epiphyseal centers

ChestExternalFeatures:
pectus excavatum
pectus carinatum

HeadAndNeckNose:
depressed nasal bridge

HeadAndNeckMouth:
cleft palate
cleft lip

CardiovascularHeart:
atrial septal defect
aortic dilatation
ventricular septal defect

RespiratoryAirways:
tracheal stenosis
tracheomalacia
bronchomalacia

NeurologicCentralNervousSystem:
spinal cord compression
mental retardation

SkeletalHands:
short metacarpals
cylindric fingers
spatulate thumbs
supernumerary carpal bones
multiple carpal ossification centers

SkinNailsHairNails:
short nails

GrowthHeight:
short stature (final adult height less than 152cm)

HeadAndNeckEyes:
hypertelorism
anterior corneal lens opacities

SkeletalSpine:
scoliosis
spina bifida occulta
cervical kyphosis
spondylolysis
cervical vertebrae hypoplasia
more
HeadAndNeckFace:
prominent forehead
flat face

GenitourinaryInternalGenitaliaMale:
cryptorchidism

SkeletalFeet:
talipes equinovarus
talipes equinovalgus
short metatarsals
supernumerary tarsal bones
delayed coalescence of calcaneal ossification centers

HeadAndNeckTeeth:
hypodontia

SkeletalSkull:
shallow orbits
flattened frontal bone
small skull base

HeadAndNeckEars:
hearing loss, conductive
malformations of the auditory ossicles

GrowthOther:
prenatal growth deficiency

SkeletalPelvis:
dislocation of the hip


Clinical features from OMIM:

150250

Human phenotypes related to Larsen Syndrome:

55 31 (show top 50) (show all 59)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 malar flattening 55 31 hallmark (90%) Very frequent (99-80%) HP:0000272
2 hypertelorism 55 31 hallmark (90%) Very frequent (99-80%) HP:0000316
3 abnormality of epiphysis morphology 55 31 occasional (7.5%) Occasional (29-5%) HP:0005930
4 finger syndactyly 55 31 occasional (7.5%) Occasional (29-5%) HP:0006101
5 intellectual disability 55 31 occasional (7.5%) Occasional (29-5%) HP:0001249
6 respiratory insufficiency 55 31 occasional (7.5%) Occasional (29-5%) HP:0002093
7 scoliosis 55 31 occasional (7.5%) Occasional (29-5%) HP:0002650
8 depressed nasal bridge 55 31 hallmark (90%) Very frequent (99-80%) HP:0005280
9 short stature 55 31 occasional (7.5%) Occasional (29-5%) HP:0004322
10 broad thumb 55 31 hallmark (90%) Very frequent (99-80%) HP:0011304
11 abnormality of the cardiovascular system 55 31 occasional (7.5%) Occasional (29-5%) HP:0001626
12 prominent forehead 55 31 hallmark (90%) Very frequent (99-80%) HP:0011220
13 cleft palate 55 31 occasional (7.5%) Occasional (29-5%) HP:0000175
14 joint hyperflexibility 55 31 hallmark (90%) Very frequent (99-80%) HP:0005692
15 cryptorchidism 55 31 occasional (7.5%) Occasional (29-5%) HP:0000028
16 flat face 55 31 hallmark (90%) Very frequent (99-80%) HP:0012368
17 conductive hearing impairment 55 31 occasional (7.5%) Occasional (29-5%) HP:0000405
18 brachydactyly 55 31 hallmark (90%) Very frequent (99-80%) HP:0001156
19 vertebral segmentation defect 55 31 occasional (7.5%) Occasional (29-5%) HP:0003422
20 craniosynostosis 55 31 occasional (7.5%) Occasional (29-5%) HP:0001363
21 short distal phalanx of finger 55 31 hallmark (90%) Very frequent (99-80%) HP:0009882
22 abnormality of the cervical spine 55 31 occasional (7.5%) Occasional (29-5%) HP:0003319
23 broad distal phalanx of finger 55 31 hallmark (90%) Very frequent (99-80%) HP:0009836
24 short nail 55 31 hallmark (90%) Very frequent (99-80%) HP:0001799
25 accessory carpal bones 55 31 frequent (33%) Frequent (79-30%) HP:0004232
26 large joint dislocations 55 31 hallmark (90%) Very frequent (99-80%) HP:0005008
27 laryngotracheomalacia 55 31 occasional (7.5%) Occasional (29-5%) HP:0008755
28 joint laxity 31 HP:0001388
29 pectus excavatum 31 HP:0000767
30 frontal bossing 31 HP:0002007
31 corneal opacity 31 HP:0007957
32 pectus carinatum 31 HP:0000768
33 beaking of vertebral bodies 31 HP:0004568
34 intrauterine growth retardation 31 HP:0001511
35 atrial septal defect 31 HP:0001631
36 hip dislocation 31 HP:0002827
37 elbow dislocation 31 HP:0003042
38 ventricular septal defect 31 HP:0001629
39 talipes equinovarus 31 HP:0001762
40 tracheal stenosis 31 HP:0002777
41 hypodontia 31 HP:0000668
42 spina bifida occulta 31 HP:0003298
43 tracheomalacia 31 HP:0002779
44 cleft upper lip 31 HP:0000204
45 hypoplastic cervical vertebrae 31 HP:0008434
46 short metacarpal 31 HP:0010049
47 short metatarsal 31 HP:0010743
48 talipes equinovalgus 31 HP:0001772
49 spinal cord compression 31 HP:0002176
50 aortic aneurysm 31 HP:0004942

GenomeRNAi Phenotypes related to Larsen Syndrome according to GeneCards Suite gene sharing:

25
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-100 9.36 FLNB
2 Increased shRNA abundance (Z-score > 2) GR00366-A-113 9.36 B4GALT7
3 Increased shRNA abundance (Z-score > 2) GR00366-A-151 9.36 FLNB
4 Increased shRNA abundance (Z-score > 2) GR00366-A-169 9.36 FLNB
5 Increased shRNA abundance (Z-score > 2) GR00366-A-177 9.36 FLNB
6 Increased shRNA abundance (Z-score > 2) GR00366-A-182 9.36 B4GALT7
7 Increased shRNA abundance (Z-score > 2) GR00366-A-183 9.36 FLNB
8 Increased shRNA abundance (Z-score > 2) GR00366-A-207 9.36 FLNB
9 Increased shRNA abundance (Z-score > 2) GR00366-A-49 9.36 B4GALT7 FLNB
10 Increased shRNA abundance (Z-score > 2) GR00366-A-85 9.36 B4GALT7

Drugs & Therapeutics for Larsen Syndrome

Search Clinical Trials , NIH Clinical Center for Larsen Syndrome

Cochrane evidence based reviews: joint dislocations

Genetic Tests for Larsen Syndrome

Genetic tests related to Larsen Syndrome:

# Genetic test Affiliating Genes
1 Larsen Syndrome, Dominant Type 28 FLNB
2 Larsen Syndrome 28
3 Joint Dislocation 28

Anatomical Context for Larsen Syndrome

MalaCards organs/tissues related to Larsen Syndrome:

38
Bone, Spinal Cord, Brain

Publications for Larsen Syndrome

Articles related to Larsen Syndrome:

(show top 50) (show all 86)
# Title Authors Year
1
Otologic manifestations of Larsen syndrome. ( 28964299 )
2017
2
GZF1 Mutations Expand the Genetic Heterogeneity of Larsen Syndrome. ( 28475863 )
2017
3
Structural Analysis of G1691S Variant in the Human Filamin B Gene Responsible for Larsen Syndrome: A Comparative Computational Approach. ( 28145583 )
2017
4
Quantification of transmission risk in a male patient with a FLNB mosaic mutation causing Larsen syndrome: Implications for genetic counseling in postzygotic mosaicism cases. ( 28639312 )
2017
5
Atlantoaxial dislocation adjacent to kyphotic deformity in a case of adult Larsen syndrome. ( 27217658 )
2016
6
Phenotype and genotype in patients with Larsen syndrome: clinical homogeneity and allelic heterogeneity in seven patients. ( 27048506 )
2016
7
Management of joint dislocations of the lower limb in Larsen syndrome: practical approach. ( 27502344 )
2016
8
EP10.44: Prenatal diagnosis of Larsen syndrome in a twin pregnancy. ( 27645408 )
2016
9
Supraglottic airway and caudal epidural for anesthetic management of a child with Larsen syndrome. ( 27275063 )
2016
10
One Stage Bilateral Total Hip Arthroplasty in Siblings with Larsen Syndrome. ( 28144369 )
2016
11
Anterior mediastinal tracheostomy with a median mandibular splitting approach in a Larsen syndrome patient with posterior cervical arthrodesis. ( 26285895 )
2015
12
Presumed Larsen syndrome in a child: a case with a 12-year follow-up. ( 25536406 )
2015
13
Dural ectasia in a child with Larsen syndrome. ( 24674893 )
2014
14
Craniosynostosis: a previously unreported association with CHST3-related skeletal dysplasia (autosomal recessive Larsen syndrome). ( 24300290 )
2014
15
Fast and early mandibular osteogenetic distraction in a 24-day-old female newborn with Larsen syndrome. ( 24820731 )
2014
16
Larsen syndrome with C3-C4 spondyloptosis and atlantoaxial dislocation in an adult. ( 23080426 )
2013
17
Pneumoperitoneum in a patient with Larsen syndrome. ( 24221813 )
2013
18
Ossicular malposition in Larsen syndrome: a case report. ( 24968394 )
2012
19
Precocious appearance of the capital femoral ossific nucleus in Larsen syndrome. ( 22552677 )
2012
20
Malignant hyperthermia-like episode in a child with Larsen syndrome. ( 22412793 )
2012
21
The management of knee dislocation in a child with Larsen syndrome. ( 21876991 )
2011
22
Larsen syndrome: a review of the literature and case report. ( 21044106 )
2010
23
Antenatal diagnosis of Larsen syndrome. ( 20589471 )
2010
24
Prenatal diagnosis of Larsen syndrome caused by a mutation in the filamin B gene. ( 19085972 )
2009
25
Significant traumatic atrophy of the spinal cord in connection with severe cervical vertebral body hypoplasia in a boy with Larsen syndrome: a case report and review of the literature. ( 19829852 )
2009
26
Larsen syndrome and malignant hyperthermia. ( 20017874 )
2009
27
Malignant hyperthermia in Larsen syndrome. ( 19691711 )
2009
28
Congenital joint dislocations caused by carbohydrate sulfotransferase 3 deficiency in recessive Larsen syndrome and humero-spinal dysostosis. ( 18513679 )
2008
29
Case report: Congenital knee dislocation in a patient with larsen syndrome and a novel filamin B mutation. ( 18322662 )
2008
30
Ulnar nerve palsy in a child with Larsen syndrome. ( 18352815 )
2008
31
Larsen syndrome. ( 18820390 )
2008
32
Management of severe cervical kyphosis in a patient with Larsen syndrome. Case report. ( 18377309 )
2008
33
Surgical treatment of cervical kyphosis in Larsen syndrome: report of 3 cases and review of the literature. ( 17202879 )
2007
34
A molecular and clinical study of Larsen syndrome caused by mutations in FLNB. ( 16801345 )
2007
35
Aneurysm of the ductus arteriosus in a patient with Larsen syndrome. ( 17006654 )
2006
36
Sporadic Larsen syndrome in a preterm female originally diagnosed as positional deformities due to oligohydramnios. ( 16450278 )
2006
37
Terminal phalangeal accessory ossification center of the thumb: an additional radiographic finding in Larsen syndrome. ( 16715218 )
2006
38
Surgical treatment of scoliosis in larsen syndrome with bilateral hip dislocation. ( 16648737 )
2006
39
Mutations responsible for Larsen syndrome cluster in the FLNB protein. ( 16648377 )
2006
40
Larsen syndrome--lethal variety. ( 16388157 )
2005
41
Long tortuous aorta in a child with Larsen syndrome. ( 15776121 )
2005
42
Sevoflurane for general anaesthetic management in a patient with Larsen syndrome. ( 14962340 )
2004
43
Cardiac arrest in a patient with Larsen syndrome under sevoflurane anesthesia. ( 15385022 )
2004
44
Three-dimensional ultrasound diagnosis of Larsen syndrome with further characterization of neurological sequelae. ( 15229923 )
2004
45
Facial features and skeletal abnormalities in Larsen syndrome--a study of three generations of a Tunisian family. ( 14745669 )
2003
46
General anaesthesia in a child with Larsen syndrome. ( 12712791 )
2003
47
Asymmetrical Larsen syndrome in a young girl: a second example of somatic mosaicism in this syndrome. ( 12725593 )
2003
48
Larsen syndrome and its anaesthetic considerations. ( 12358662 )
2002
49
Larsen syndrome associated with severe congenital hydrocephalus. ( 11837607 )
2001
50
Obstetric anesthetic management of a parturient with Larsen syndrome and short stature. ( 11323359 )
2001

Variations for Larsen Syndrome

UniProtKB/Swiss-Prot genetic disease variations for Larsen Syndrome:

71 (show all 12)
# Symbol AA change Variation ID SNP ID
1 FLNB p.Phe161Cys VAR_033069 rs80356506
2 FLNB p.Gly168Ser VAR_033070 rs80356504
3 FLNB p.Glu227Lys VAR_033075 rs80356508
4 FLNB p.Leu234Val VAR_033076 rs80356507
5 FLNB p.Gly361Ser VAR_033078 rs80356509
6 FLNB p.Gly363Glu VAR_033079 rs80356510
7 FLNB p.Leu1431Arg VAR_033081 rs80356511
8 FLNB p.Gly1586Arg VAR_033083 rs80356513
9 FLNB p.Val1592Asp VAR_033084 rs80356514
10 FLNB p.Pro1603Leu VAR_033085 rs80356515
11 FLNB p.Gly1691Ser VAR_033086 rs80356503
12 FLNB p.Gly1834Arg VAR_033087 rs80356516

ClinVar genetic disease variations for Larsen Syndrome:

6 (show all 12)
# Gene Variation Type Significance SNP ID Assembly Location
1 FLNB NM_001457.3(FLNB): c.1081G> A (p.Gly361Ser) single nucleotide variant Pathogenic rs80356509 GRCh37 Chromosome 3, 58083638: 58083638
2 FLNB NM_001457.3(FLNB): c.1088G> A (p.Gly363Glu) single nucleotide variant Pathogenic rs80356510 GRCh37 Chromosome 3, 58083645: 58083645
3 FLNB NM_001457.3(FLNB): c.4292T> G (p.Leu1431Arg) single nucleotide variant Pathogenic rs80356511 GRCh37 Chromosome 3, 58116537: 58116537
4 FLNB NM_001457.3(FLNB): c.4711_4713delAAT (p.Asn1571del) deletion Pathogenic rs80356512 GRCh37 Chromosome 3, 58121745: 58121747
5 FLNB NM_001457.3(FLNB): c.4775T> A (p.Val1592Asp) single nucleotide variant Pathogenic rs80356514 GRCh37 Chromosome 3, 58121809: 58121809
6 FLNB NM_001457.3(FLNB): c.4808C> T (p.Pro1603Leu) single nucleotide variant Pathogenic rs80356515 GRCh37 Chromosome 3, 58121842: 58121842
7 FLNB NM_001457.3(FLNB): c.5500G> A (p.Gly1834Arg) single nucleotide variant Pathogenic rs80356516 GRCh37 Chromosome 3, 58131722: 58131722
8 FLNB NM_001457.3(FLNB): c.700C> G (p.Leu234Val) single nucleotide variant Pathogenic rs80356507 GRCh37 Chromosome 3, 58067416: 58067416
9 FLNB NM_001457.3(FLNB): c.482T> G (p.Phe161Cys) single nucleotide variant Pathogenic rs80356506 GRCh37 Chromosome 3, 58062962: 58062962
10 FLNB NM_001457.3(FLNB): c.4756G> A (p.Gly1586Arg) single nucleotide variant Pathogenic rs80356513 GRCh37 Chromosome 3, 58121790: 58121790
11 FLNB NM_001457.3(FLNB): c.679G> A (p.Glu227Lys) single nucleotide variant Pathogenic rs80356508 GRCh37 Chromosome 3, 58067395: 58067395
12 FLNB NM_001457.3(FLNB): c.5071G> A (p.Gly1691Ser) single nucleotide variant Pathogenic rs80356503 GRCh37 Chromosome 3, 58124218: 58124218

Expression for Larsen Syndrome

Search GEO for disease gene expression data for Larsen Syndrome.

GO Terms for Larsen Syndrome

Cellular components related to Larsen Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 Golgi membrane GO:0000139 8.8 B4GALT7 CHST3 COL7A1

Biological processes related to Larsen Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 carbohydrate metabolic process GO:0005975 8.62 B4GALT7 CHST3

Sources for Larsen Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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