LWD
MCID: LRW001
MIFTS: 43

Leri-Weill Dyschondrosteosis (LWD)

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

Aliases & Classifications for Leri-Weill Dyschondrosteosis

MalaCards integrated aliases for Leri-Weill Dyschondrosteosis:

Name: Leri-Weill Dyschondrosteosis 56 12 25 58 73 29 13 54 6 15
Lwd 56 52 25 73
Léri-Weill Dyschondrosteosis 74 52 25
Dyschondrosteosis 56 52 25
Dco 56 52 25
Dyschondrosteosis, Leri-Weill 39
Leri Weill Dyschondrosteosis 52
Dyschondrosteosis; Dco 56
Leri-Weill Syndrome 58
Leri-Weil Syndrome 43

Characteristics:

Orphanet epidemiological data:

58
leri-weill dyschondrosteosis
Inheritance: Autosomal dominant; Age of onset: Neonatal; Age of death: normal life expectancy;

OMIM:

56
Inheritance:
pseudoautosomal dominant

Miscellaneous:
female preponderance
madelung deformity more frequent and more severe in females
shox is located in the pseudoautosomal region of the x and y chromosomes


HPO:

31
leri-weill dyschondrosteosis:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 58  
Rare bone diseases
Developmental anomalies during embryogenesis


External Ids:

Disease Ontology 12 DOID:0060847
OMIM 56 127300
MeSH 43 C537119
NCIt 49 C126560
SNOMED-CT 67 17818006
MESH via Orphanet 44 C537119
ICD10 via Orphanet 33 Q77.8
UMLS via Orphanet 72 C0265309
Orphanet 58 ORPHA240
UMLS 71 C0265309

Summaries for Leri-Weill Dyschondrosteosis

NIH Rare Diseases : 52 Leri Weill dyschondrosteosis (LWD) is a skeletal dysplasia characterized by short stature and an abnormality of the wrist bones called Madelung deformity . Short stature is present from birth due to shortening of the long bones in the legs. Madelung deformity typically develops during mid-to-late childhood and may progress during puberty. People with this condition often experience pain in their wrists or arms. The severity of Leri Weill dyschondrosteosis varies among affected individuals, although the signs and symptoms of this condition are generally more severe in females. Other features of Leri Weill dyschondrosteosis can include increased muscle size, bowing of a bone in the leg called tibia, elbow abnormalities, scoliosis , and high-arched palate. Intelligence is not affected by this condition. Most cases of Leri Weill dyschondrosteosis are caused by mutations in or near the SHOX gene . The cause of the disorder remains unknown in those cases not related to the SHOX gene . Leri Weill dyschondrosteosis follows a pseudoautosomal dominant pattern of inheritance, which is similar to the autosomal dominant inheritance. LWD is part of a group of diseases caused by deficiency of the SHOX gene , which includes a form or SHOX related short stature without additional problems.

MalaCards based summary : Leri-Weill Dyschondrosteosis, also known as lwd, is related to madelung deformity and langer mesomelic dysplasia. An important gene associated with Leri-Weill Dyschondrosteosis is SHOX (Short Stature Homeobox). Affiliated tissues include bone, skeletal muscle and eye, and related phenotypes are depressed nasal bridge and wide nasal bridge

Disease Ontology : 12 An osteochondrodysplasia characterized by abnormal shortening of the forearms and lower legs, abnormal misalignment of the wrist (Madelung deformity of the wrist), and associated short stature and has material basis in heterozygous defects in the pseudoautosomal genes SHOX or SHOXY or by deletion of the SHOX downstream regulatory domain.

Genetics Home Reference : 25 Léri-Weill dyschondrosteosis is a disorder of bone growth. Affected individuals typically have shortening of the long bones in the arms and legs (mesomelia). As a result of the shortened leg bones, people with Leri-Weill dyschondrosteosis typically have short stature. Most people with the condition also have an abnormality of the wrist and forearm bones called Madelung deformity, which may cause pain and limit wrist movement. This abnormality usually appears in childhood or early adolescence. Other features of Léri-Weill dyschondrosteosis can include increased muscle mass (muscle hypertrophy); bowing of a bone in the lower leg called the tibia; a greater-than-normal angling of the elbow away from the body (increased carrying angle); and a high arched palate. Léri-Weill dyschondrosteosis occurs in both males and females, although its signs and symptoms tend to be more severe in females. Researchers believe that the more severe features may result from hormonal differences.

OMIM : 56 Leri-Weill dyschondrosteosis (LWD) is a dominantly inherited skeletal dysplasia characterized by short stature, mesomelia, and Madelung wrist deformity. Although the disorder occurs in both sexes, it is usually more severe in females, perhaps due to sex difference in estrogen levels. However, pubertal development and fertility are generally normal in both sexes with the disorder (summary by Ross et al., 2005). The Madelung wrist deformity includes deformity of the distal radius and ulna and proximal carpal bones (Langer, 1965). See also Langer mesomelic dysplasia (LMD; 249700), a more severe phenotype that results from homozygous defect in the SHOX or SHOXY genes. (127300)

UniProtKB/Swiss-Prot : 73 Leri-Weill dyschondrosteosis: Dominantly inherited skeletal dysplasia characterized by moderate short stature predominantly because of short mesomelic limb segments. It is often associated with the Madelung deformity of the wrist, comprising bowing of the radius and dorsal dislocation of the distal ulna.

Wikipedia : 74 Léri-Weill dyschondrosteosis or LWD is a rare pseudoautosomal dominant genetic disorder which results in... more...

Related Diseases for Leri-Weill Dyschondrosteosis

Diseases related to Leri-Weill Dyschondrosteosis via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 44)
# Related Disease Score Top Affiliating Genes
1 madelung deformity 33.0 SHOX LOC108251803 LOC108251802
2 langer mesomelic dysplasia 30.8 SHOX LOC107652445 CNE9 CNE8 CNE7 CNE6
3 hypochondroplasia 30.7 SHOX FGFR3
4 turner syndrome 30.6 SRY SHOX2 SHOX
5 achondroplasia 30.4 SHOX FGFR3
6 short stature, idiopathic, x-linked 30.2 SHOX LOC107652445
7 shox deficiency disorders 29.6 SHOX CNE9 CNE8 CNE7 CNE6 CNE5
8 odontochondrodysplasia 29.3 SHOX2 SHOX FGFR3
9 dyschondrosteosis and nephritis 11.7
10 ulna and fibula, hypoplasia of 11.7
11 gonadal dysgenesis 11.0
12 mesomelia 10.8
13 scoliosis 10.7
14 dwarfism 10.6
15 aortic valve disease 1 10.5
16 migraine with or without aura 1 10.5
17 lymphoma, hodgkin, x-linked pseudoautosomal 10.5
18 acid-labile subunit deficiency 10.5
19 lymphoma 10.5
20 craniosynostosis 10.5
21 neurofibromatosis 10.5
22 overgrowth syndrome 10.5
23 leukemia, acute lymphoblastic 10.4
24 leukemia, acute lymphoblastic 3 10.4
25 noma 10.3
26 female breast cancer 10.2
27 pneumothorax 10.2
28 pulmonary emphysema 10.2
29 ichthyosis 10.2
30 cerulean cataract 10.2
31 pfeiffer syndrome 10.0
32 spondylocostal dysostosis 5 10.0
33 mccune-albright syndrome 10.0
34 osteogenic sarcoma 10.0
35 ichthyosis, x-linked 10.0
36 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.0
37 bone disease 10.0
38 blount's disease 10.0
39 ankylosis 10.0
40 precocious puberty 10.0
41 skeletal dysplasias 10.0
42 acromesomelic dysplasia, maroteaux type 10.0 SHOX FGFR3
43 acromesomelic dysplasia 10.0 SHOX FGFR3
44 autism 8.8 CNE9 CNE8 CNE7 CNE6 CNE5 CNE4

Graphical network of the top 20 diseases related to Leri-Weill Dyschondrosteosis:



Diseases related to Leri-Weill Dyschondrosteosis

Symptoms & Phenotypes for Leri-Weill Dyschondrosteosis

Human phenotypes related to Leri-Weill Dyschondrosteosis:

58 31 (show all 48)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 depressed nasal bridge 58 31 hallmark (90%) Very frequent (99-80%) HP:0005280
2 wide nasal bridge 58 31 hallmark (90%) Very frequent (99-80%) HP:0000431
3 joint stiffness 58 31 hallmark (90%) Very frequent (99-80%) HP:0001387
4 abnormality of the metaphysis 58 31 hallmark (90%) Very frequent (99-80%) HP:0000944
5 abnormality of the hip bone 58 31 hallmark (90%) Very frequent (99-80%) HP:0003272
6 diaphyseal thickening 58 31 hallmark (90%) Very frequent (99-80%) HP:0005019
7 madelung deformity 58 31 hallmark (90%) Very frequent (99-80%) HP:0003067
8 abnormality of femur morphology 58 31 hallmark (90%) Very frequent (99-80%) HP:0002823
9 brachydactyly 58 31 hallmark (90%) Very frequent (99-80%) HP:0001156
10 clinodactyly of the 5th finger 58 31 hallmark (90%) Very frequent (99-80%) HP:0004209
11 exostoses 58 31 hallmark (90%) Very frequent (99-80%) HP:0100777
12 genu varum 58 31 hallmark (90%) Very frequent (99-80%) HP:0002970
13 micromelia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002983
14 hypoplastic fingernail 58 31 hallmark (90%) Very frequent (99-80%) HP:0001804
15 hypoplasia of the ulna 58 31 hallmark (90%) Very frequent (99-80%) HP:0003022
16 cone-shaped epiphysis 58 31 hallmark (90%) Very frequent (99-80%) HP:0010579
17 disproportionate short-limb short stature 58 31 hallmark (90%) Very frequent (99-80%) HP:0008873
18 hypoplasia of the radius 58 31 hallmark (90%) Very frequent (99-80%) HP:0002984
19 aplastic/hypoplastic toenail 58 31 hallmark (90%) Very frequent (99-80%) HP:0010624
20 abnormality of the humerus 58 31 hallmark (90%) Very frequent (99-80%) HP:0003063
21 patellar aplasia 58 31 hallmark (90%) Very frequent (99-80%) HP:0006443
22 tibial bowing 58 31 hallmark (90%) Very frequent (99-80%) HP:0002982
23 abnormality of the carpal bones 58 31 hallmark (90%) Very frequent (99-80%) HP:0001191
24 radial bowing 58 31 hallmark (90%) Very frequent (99-80%) HP:0002986
25 mesomelia 58 31 hallmark (90%) Very frequent (99-80%) HP:0003027
26 ulnar bowing 58 31 hallmark (90%) Very frequent (99-80%) HP:0003031
27 short tibia 58 31 hallmark (90%) Very frequent (99-80%) HP:0005736
28 limited wrist movement 58 31 hallmark (90%) Very frequent (99-80%) HP:0006248
29 dorsal subluxation of ulna 58 31 hallmark (90%) Very frequent (99-80%) HP:0006459
30 genu valgum 58 31 frequent (33%) Frequent (79-30%) HP:0002857
31 elbow dislocation 58 31 frequent (33%) Frequent (79-30%) HP:0003042
32 abnormality of calvarial morphology 58 31 frequent (33%) Frequent (79-30%) HP:0002648
33 scoliosis 31 HP:0002650
34 abnormality of the ulna 58 Very frequent (99-80%)
35 high palate 31 HP:0000218
36 short 4th metacarpal 31 HP:0010044
37 short toe 31 HP:0001831
38 limited elbow movement 31 HP:0002996
39 abnormality of tibia morphology 58 Very frequent (99-80%)
40 abnormality of epiphysis morphology 58 Very frequent (99-80%)
41 abnormality of pelvic girdle bone morphology 58 Very frequent (99-80%)
42 skeletal muscle hypertrophy 31 HP:0003712
43 coxa valga 31 HP:0002673
44 fibular hypoplasia 31 HP:0003038
45 abnormality of the radius 58 Very frequent (99-80%)
46 multiple exostoses 31 HP:0002762
47 abnormal metatarsal morphology 31 HP:0001832
48 increased carrying angle 31 HP:0003102

Symptoms via clinical synopsis from OMIM:

56
Skeletal Spine:
scoliosis

Head And Neck Mouth:
high-arched palate

Skeletal Hands:
madelung wrist deformity (74% of lwd patients)
limited wrist mobility

Skeletal Limbs:
mesomelia
dorsal subluxation of ulna
increased carrying angle
limited elbow mobility
bowing of the radius
more
Growth Height:
short stature, disproportionate
adult height 135cm to normal

Clinical features from OMIM:

127300

Drugs & Therapeutics for Leri-Weill Dyschondrosteosis

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 X-chromosome Inactivation, Epigenetics and the Transcriptome Completed NCT01678261

Search NIH Clinical Center for Leri-Weill Dyschondrosteosis

Cochrane evidence based reviews: leri-weil syndrome

Genetic Tests for Leri-Weill Dyschondrosteosis

Genetic tests related to Leri-Weill Dyschondrosteosis:

# Genetic test Affiliating Genes
1 Leri-Weill Dyschondrosteosis 29 SHOX

Anatomical Context for Leri-Weill Dyschondrosteosis

MalaCards organs/tissues related to Leri-Weill Dyschondrosteosis:

40
Bone, Skeletal Muscle, Eye

Publications for Leri-Weill Dyschondrosteosis

Articles related to Leri-Weill Dyschondrosteosis:

(show top 50) (show all 186)
# Title Authors PMID Year
1
Identification of the first recurrent PAR1 deletion in Léri-Weill dyschondrosteosis and idiopathic short stature reveals the presence of a novel SHOX enhancer. 6 56 61
22791839 2012
2
Identification of a Gypsy SHOX mutation (p.A170P) in Léri-Weill dyschondrosteosis and Langer mesomelic dysplasia. 61 56 6
21712857 2011
3
SHOX point mutations in dyschondrosteosis. 54 56 6
11403039 2001
4
Mutations in short stature homeobox containing gene (SHOX) in dyschondrosteosis but not in hypochondroplasia. 56 6 54
11030412 2000
5
SHOX mutations in dyschondrosteosis (Leri-Weill syndrome). 54 6 56
9590292 1998
6
Mutation and deletion of the pseudoautosomal gene SHOX cause Leri-Weill dyschondrosteosis. 61 56 6
9590293 1998
7
Long-range conserved non-coding SHOX sequences regulate expression in developing chicken limb and are associated with short stature phenotypes in human patients. 56 61 54
17200153 2007
8
A novel class of Pseudoautosomal region 1 deletions downstream of SHOX is associated with Leri-Weill dyschondrosteosis. 54 61 56
16175500 2005
9
The phenotype of short stature homeobox gene (SHOX) deficiency in childhood: contrasting children with Leri-Weill dyschondrosteosis and Turner syndrome. 56 54 61
16227037 2005
10
SHOX haploinsufficiency and Leri-Weill dyschondrosteosis: prevalence and growth failure in relation to mutation, sex, and degree of wrist deformity. 6 54 61
15356038 2004
11
A novel point mutation A170P in the SHOX gene defines impaired nuclear translocation as a molecular cause for Léri-Weill dyschondrosteosis and Langer dysplasia. 54 56 61
15173249 2004
12
Impairment of SHOX nuclear localization as a cause for Léri-Weill syndrome. 56 61 54
15173321 2004
13
Loss of the SHOX gene associated with Leri-Weill dyschondrosteosis in a 45,X male. 61 54 56
10507731 1999
14
SHOX triggers the lysosomal pathway of apoptosis via oxidative stress. 61 6
24186869 2014
15
SHOX Deficiency Disorders 61 6
20301394 2005
16
Auxology is a valuable instrument for the clinical diagnosis of SHOX haploinsufficiency in school-age children with unexplained short stature. 61 56
14557470 2003
17
Mesomelic and rhizomelic short stature: The phenotype of combined Leri-Weill dyschondrosteosis and achondroplasia or hypochondroplasia. 61 56
12476453 2003
18
Pseudodominant inheritance of Langer mesomelic dysplasia caused by a SHOX homeobox missense mutation. 61 6
12116253 2002
19
Complete SHOX deficiency causes Langer mesomelic dysplasia. 61 6
12116254 2002
20
SHOX nullizygosity and haploinsufficiency in a Japanese family: implication for the development of Turner skeletal features. 6 61
11889214 2002
21
Phenotypes Associated with SHOX Deficiency. 56 61
11739418 2001
22
X/Y translocation in a family with Leri-Weill dyschondrosteosis. 56 61
10543407 1999
23
Molecular genetic analysis of a family with a history of Hodgkin's disease and dyschondrosteosis. 56 61
7769845 1995
24
Enhancer deletions of the SHOX gene as a frequent cause of short stature: the essential role of a 250 kb downstream regulatory domain. 56
19578035 2009
25
The homozygous deletion of the 3' enhancer of the SHOX gene causes Langer mesomelic dysplasia. 6
17935511 2007
26
Identification and characterization of different SHOX gene deletions in patients with Leri-Weill dyschondrosteosys by MLPA assay. 56
17091221 2007
27
SHOX deficiency phenotypes. 56
12915706 2003
28
A t(2;8) balanced translocation with breakpoints near the human HOXD complex causes mesomelic dysplasia and vertebral defects. 56
11944980 2002
29
SHOX haploinsufficiency and overdosage: impact of gonadal function status. 56
11134233 2001
30
Phenotypic variation and genetic heterogeneity in Léri-Weill syndrome. 56
10713888 2000
31
The gene for mesomelic dysplasia Kantaputra type is mapped to chromosome 2q24-q32. 56
9609995 1998
32
Linkage of skeletal dysplasia gene to t(2;8)(q32;p13) chromosome translocation breakpoint. 56
6486174 1984
33
Multiple skeletal familial abnormalities associated with balanced reciprocal translocation 2;8(q32;p13). 56
6660251 1983
34
A possibly new form of familial bone dysplasia resembling dyschondrosteosis. 56
6844051 1983
35
Clinical variation in dyschondrosteosis. A report on 13 individuals in 8 families. 56
7096409 1982
36
Mesomelic dysplasia, type Langer--a homozygous state for dyschondrosteosis. 56
7428776 1980
37
Sex-influenced expression of Madelung's deformity in a family of dyschondrosteosis. 56
7365762 1980
38
Langer type of mesomelic dwarfism as the possible homozygous expression of dyschondrosteosis. 56
429003 1979
39
Mesomelic dwarfism as the homozygous expression of dyschondrosteosis. 56
1121969 1975
40
Dyschondrosteosis (mesomelic dwarfism)--a family study. 56
4433973 1974
41
Dyschondrosteosis. A Mexican family with two affected males. 56
5054807 1972
42
Dyschondrosteose. Mesomelic dwarfism of Lwei and Weill. 56
5493830 1970
43
Madelung's deformity with conductive hearing loss. 56
5410085 1970
44
Madelung's deformity: observations in 17 patients. 56
5350668 1969
45
[Familial dyschondrosteosis. Study of 3 cases (mother and her 2 sons)]. 56
4301239 1968
46
Dyschondrosteosis. The most common cause of Madelung's deformity. 56
5903314 1966
47
DYSCHONDROSTEOSIS, A HEREDITABLE BONE DYSPLASIA WITH CHARACTERISTIC ROENTGENOGRAPHIC FEATURES. 56
14344358 1965
48
MADELUNG'S DEFORMITY. 56
17857243 1938
49
Imaging of SHOX-associated anomalies. 61 54
19724992 2009
50
Cryptic intragenic deletion of the SHOX gene in a family with Léri-Weill dyschondrosteosis detected by Multiplex Ligation-Dependent Probe Amplification (MLPA). 54 61
19169498 2008

Variations for Leri-Weill Dyschondrosteosis

ClinVar genetic disease variations for Leri-Weill Dyschondrosteosis:

6 (show all 14) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 SHOX NM_000451.3(SHOX):c.508G>C (p.Ala170Pro)SNV Pathogenic 29994 rs397514461 X:601577-601577 X:640842-640842
2 SHOX NM_000451.3(SHOX):c.509C>A (p.Ala170Asp)SNV Pathogenic 29995 rs397514462 X:601578-601578 X:640843-640843
3 SHOX SHOX, 47.5-KB DEL, DOWNSTREAM ENHANCERdeletion Pathogenic 66087
4 SHOX SHOX, 1.1-MB DELdeletion Pathogenic 9884
5 SHOX NM_000451.3(SHOX):c.877T>C (p.Ter293Arg)SNV Pathogenic 9883 rs137852559 X:605369-605369 X:644634-644634
6 SHOX NM_000451.3(SHOX):c.304G>T (p.Glu102Ter)SNV Pathogenic 9882 rs137852558 X:595379-595379 X:634644-634644
7 SHOX NM_000451.3(SHOX):c.502C>T (p.Arg168Trp)SNV Pathogenic 9879 rs137852557 X:601571-601571 X:640836-640836
8 SHOX NM_000451.3(SHOX):c.517C>T (p.Arg173Cys)SNV Pathogenic 9878 rs137852556 X:601586-601586 X:640851-640851
9 SHOX SHOX, 1-BP DEL, 1272Gdeletion Pathogenic 9877
10 SHOX NM_000451.3(SHOX):c.458G>T (p.Arg153Leu)SNV Pathogenic 9876 rs137852555 X:595533-595533 X:634798-634798
11 SHOX NM_000451.3(SHOX):c.394C>G (p.Leu132Val)SNV Pathogenic 9875 rs137852554 X:595469-595469 X:634734-634734
12 SHOX SHOX, DELdeletion Pathogenic 9874
13 SHOX NM_000451.3(SHOX):c.597C>G (p.Tyr199Ter)SNV Pathogenic 9873 rs137852553 X:601786-601786 X:641051-641051
14 CNE7 , LOC108251802 deletion Uncertain significance 560137 X:781071-819225 X:820337-843143

UniProtKB/Swiss-Prot genetic disease variations for Leri-Weill Dyschondrosteosis:

73
# Symbol AA change Variation ID SNP ID
1 SHOX p.Arg173Cys VAR_012346 rs137852556
2 SHOX p.Leu132Val VAR_019414 rs137852554
3 SHOX p.Arg153Leu VAR_019415 rs137852555

Expression for Leri-Weill Dyschondrosteosis

Search GEO for disease gene expression data for Leri-Weill Dyschondrosteosis.

Pathways for Leri-Weill Dyschondrosteosis

GO Terms for Leri-Weill Dyschondrosteosis

Biological processes related to Leri-Weill Dyschondrosteosis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 chondrocyte differentiation GO:0002062 8.96 SHOX2 FGFR3
2 skeletal system development GO:0001501 8.8 SHOX2 SHOX FGFR3

Sources for Leri-Weill Dyschondrosteosis

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72 UMLS via Orphanet
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