MCID: LNG040
MIFTS: 34

Langer Mesomelic Dysplasia

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

Aliases & Classifications for Langer Mesomelic Dysplasia

MalaCards integrated aliases for Langer Mesomelic Dysplasia:

Name: Langer Mesomelic Dysplasia 53 49 24 55 71 13 51
Lmd 53 24 71
Mesomelic Dwarfism of the Hypoplastic Ulna, Fibula, and Mandible Type 53 24
Dyschondrosteosis, Homozygous 53 49
Mesomelic Dwarfism of the Hypoplastic Ulna, Fibula and Mandible Type 49
Langer Mesomelic Dysplasia Syndrome 28
Mesomelic Dwarfism, Langer Type 55
Dyschondrosteosis Homozygous 24
Langer Mesomelic Dwarfism 24

Characteristics:

Orphanet epidemiological data:

55
langer mesomelic dysplasia
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: normal life expectancy;

OMIM:

53
Inheritance:
autosomal recessive

Miscellaneous:
lmd is the homozygous form of the less severe leri-weill dyschondrosteosis


HPO:

31
langer mesomelic dysplasia:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 53 249700
Orphanet 55 ORPHA2632
MESH via Orphanet 42 C537267
UMLS via Orphanet 70 C0432230
ICD10 via Orphanet 33 Q87.1
MedGen 39 C0432230

Summaries for Langer Mesomelic Dysplasia

NIH Rare Diseases : 49 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 2632Disease definitionLanger mesomelic dysplasia (LMD) is characterized by severe disproportionate short stature with mesomelic and rhizomelic shortening of the upper and lower limbs.EpidemiologyPrevalence is unknown but less than 70 cases have been reported in the literature so far.Clinical descriptionLMD represents a more severe form of Léri-Weill dyschondrosteosis (LWD; see this term) with severely shortened long bones of the limbs (involving both the middle and proximal segments), deformity of the humeral head, angulation of the radial shaft, carpal distortion, a short femoral neck, and absence or hypoplasia of the proximal half of the fibula. Mild hypoplasia of the mandible has been reported in some cases. In contrast to LWD, Madelung deformity (see this term) is not typically present in LMD. Associated malformations are rare and intellect is normal in almost all reported LMD cases.EtiologyLMD is inherited in a pseudoautosomal recessive manner and is associated with homozygous or compound heterozygousmutations and deletions of the Short stature HomeobOX (SHOX) gene (which maps to the pseudoautosomal region 1 (PAR1) of the sex chromosomes; Xp22.33 and Yp11.32) or of the downstream PAR1 (where SHOX enhancer elements are located). LMD is part of a spectrum of disorders (ranging from the most severe, LMD, to LWD, isolated Madelung deformity and so-called idiopathic short stature; see these terms), all associated with SHOX/PAR1 anomalies. The prevalence of SHOX/PAR1 mutations is estimated at 1/1000.Diagnostic methodsDiagnosis of LMD may be suspected on the basis of the clinical and radiologic findings and can be confirmed by molecular analysis (microsatellite analysis, FISH or, preferably, MLPA for PAR1 deletions, high resolution melting (HRM), dHPLC and/or DNA sequencing for point mutations, small deletions and insertions of SHOX).Differential diagnosisLMD may also be suspected by ultrasound at 20 weeks of gestation and at this stage should be differentiated from femur-fibula-ulna (FFU) complex and the Reinhardt-Pfeiffer form of mesomelic dysplasia (see these terms).Antenatal diagnosisPrenatal genetic testing is available; however, requests for testing for these disorders are uncommon but are more frequent for LMD.Genetic counselingGenetic counseling should be proposed and families should be informed that SHOX/PAR1 anomalies are inherited in a pseudoautosomal dominant manner. Each child of an individual with LWD has a 50% chance of inheriting the mutation. If both parents have LWD, the offspring have a 50% chance of having LWD, a 25% chance of having LMD, and a 25% chance of having neither condition. All children of an individual with LMD and an unaffected parent will present with LWD.Management and treatmentThere is no effective treatment for LMD. The symptomatic medical management of children with LMD begins at birth and continues into adulthood. Careful monitoring of height, weight, and head circumference is essential.PrognosisThe short stature and limb deformities are severe but life expectancy is normal.Visit the Orphanet disease page for more resources. Last updated: 5/15/2009

MalaCards based summary : Langer Mesomelic Dysplasia, also known as lmd, is related to leri-weill dyschondrosteosis and ulna and fibula, hypoplasia of, and has symptoms including abnormality of epiphysis morphology, high palate and bowing of the long bones. An important gene associated with Langer Mesomelic Dysplasia is SHOX (Short Stature Homeobox). Affiliated tissues include bone and testes.

Genetics Home Reference : 24 Langer mesomelic dysplasia is a disorder of bone growth. Affected individuals typically have extreme shortening of the long bones in the arms and legs (mesomelia). As a result of the shortened leg bones, people with Langer mesomelic dysplasia have very short stature. A bone in the forearm called the ulna and a bone in the lower leg called the fibula are often underdeveloped or absent, while other bones in the forearm (the radius) and lower leg (the tibia) are unusually short, thick, and curved. Some people with Langer mesomelic dysplasia also have an abnormality of the wrist and forearm bones called Madelung deformity, which may cause pain and limit wrist movement. Additionally, some affected individuals have mild underdevelopment of the lower jaw bone (mandible).

OMIM : 53 Langer mesomelic dysplasia (LMD) is characterized by severe limb aplasia or severe hypoplasia of the ulna and fibula, and a thickened and curved radius and tibia. These changes can result in displacement deformities of the hands and feet. Hypoplasia of the mandible is also observed (Langer, 1967). See also Leri-Weill dyschondrosteosis (127300), a less severe phenotype that results from heterozygous defect in the SHOX or SHOXY genes. (249700)

UniProtKB/Swiss-Prot : 71 Langer mesomelic dysplasia: Autosomal recessive rare skeletal dysplasia characterized by severe short stature owing to shortening and maldevelopment of the mesomelic and rhizomelic segments of the limbs. Associated malformations are rarely reported and intellect is normal in all affected subjects reported to date.

Wikipedia : 72 Langer mesomelic dysplasia (LMD) is a rare congenital disorder characterized by an altered bone... more...

Related Diseases for Langer Mesomelic Dysplasia

Diseases related to Langer Mesomelic Dysplasia via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 leri-weill dyschondrosteosis 31.4 CNE5 CNE7 CNE8 SHOX
2 ulna and fibula, hypoplasia of 11.2
3 mesomelia-synostoses syndrome 11.2
4 dwarfism 10.4
5 turner syndrome 10.1
6 ring chromosome y syndrome 10.1
7 autism 7.2 CNE-2 CNE-3 CNE-5 CNE4 CNE5 CNE6

Graphical network of the top 20 diseases related to Langer Mesomelic Dysplasia:



Diseases related to Langer Mesomelic Dysplasia

Symptoms & Phenotypes for Langer Mesomelic Dysplasia

Symptoms via clinical synopsis from OMIM:

53
Head And Neck Face:
micrognathia

Skeletal Limbs:
mesomelia
rudimentary fibula
short femoral neck
short, broad ulna
dorsolateral bowed, short radii
more
Skeletal Spine:
increased lumbar lordosis

Skeletal Hands:
madelung deformity

Neurologic Central Nervous System:
normal intelligence

Growth Height:
short stature, disproportionate mesomelic


Clinical features from OMIM:

249700

Human phenotypes related to Langer Mesomelic Dysplasia:

55 31 (show all 23)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 abnormality of epiphysis morphology 55 31 hallmark (90%) Very frequent (99-80%) HP:0005930
2 high palate 55 31 hallmark (90%) Very frequent (99-80%) HP:0000218
3 bowing of the long bones 55 31 hallmark (90%) Very frequent (99-80%) HP:0006487
4 abnormality of the ulna 55 31 hallmark (90%) Very frequent (99-80%) HP:0002997
5 micromelia 55 31 hallmark (90%) Very frequent (99-80%) HP:0002983
6 madelung deformity 55 31 hallmark (90%) Very frequent (99-80%) HP:0003067
7 severe short stature 55 31 hallmark (90%) Very frequent (99-80%) HP:0003510
8 ulnar deviation of finger 55 31 hallmark (90%) Very frequent (99-80%) HP:0009465
9 abnormality of the carpal bones 55 31 hallmark (90%) Very frequent (99-80%) HP:0001191
10 mesomelic/rhizomelic limb shortening 55 31 hallmark (90%) Very frequent (99-80%) HP:0005026
11 aplasia/hypoplasia of the fibula 55 31 hallmark (90%) Very frequent (99-80%) HP:0006492
12 short femoral neck 55 31 hallmark (90%) Very frequent (99-80%) HP:0100864
13 micrognathia 31 HP:0000347
14 disproportionate short-limb short stature 55 Very frequent (99-80%)
15 hypoplasia of the ulna 31 HP:0003022
16 hypoplasia of the radius 31 HP:0002984
17 lumbar hyperlordosis 31 HP:0002938
18 mesomelia 31 HP:0003027
19 radial bowing 31 HP:0002986
20 rudimentary fibula 31 HP:0006381
21 mesomelic short stature 31 HP:0008845
22 shortening of the tibia 31 HP:0006436
23 broad ulna 31 HP:0003993

Drugs & Therapeutics for Langer Mesomelic Dysplasia

Search Clinical Trials , NIH Clinical Center for Langer Mesomelic Dysplasia

Genetic Tests for Langer Mesomelic Dysplasia

Genetic tests related to Langer Mesomelic Dysplasia:

# Genetic test Affiliating Genes
1 Langer Mesomelic Dysplasia Syndrome 28

Anatomical Context for Langer Mesomelic Dysplasia

MalaCards organs/tissues related to Langer Mesomelic Dysplasia:

38
Bone, Testes

Publications for Langer Mesomelic Dysplasia

Articles related to Langer Mesomelic Dysplasia:

(show all 14)
# Title Authors Year
1
Compound heterozygous deletions in pseudoautosomal region 1 in an infant with mild manifestations of langer mesomelic dysplasia. ( 24311385 )
2014
2
Langer Mesomelic Dysplasia in Early Fetuses: Two Cases and a Literature Review. ( 23883335 )
2013
3
Clinical utility gene card for: Leri-Weill dyschondrosteosis (LWD) and Langer mesomelic dysplasia (LMD). ( 22510850 )
2012
4
First-trimester ultrasonographic diagnosis of Langer mesomelic dysplasia in a previously affected family. ( 21692083 )
2011
5
Identification of a Gypsy SHOX mutation (p.A170P) in LAcri-Weill dyschondrosteosis and Langer mesomelic dysplasia. ( 21712857 )
2011
6
Effect of growth hormone therapy on severe short stature and skeletal deformities in a patient with combined Turner syndrome and Langer mesomelic dysplasia. ( 19850687 )
2009
7
Compound heterozygosity of SHOX-encompassing and downstream PAR1 deletions results in Langer mesomelic dysplasia (LMD). ( 17394206 )
2007
8
The homozygous deletion of the 3' enhancer of the SHOX gene causes Langer mesomelic dysplasia. ( 17935511 )
2007
9
Microdeletion in the SHOX 3' region associated with skeletal phenotypes of Langer mesomelic dysplasia in a 45,X/46,X,r(X) infant and Leri-Weill dyschondrosteosis in her 46,XX mother: implication for the SHOX enhancer. ( 16007631 )
2005
10
Pseudodominant inheritance of Langer mesomelic dysplasia caused by a SHOX homeobox missense mutation. ( 12116253 )
2002
11
Complete SHOX deficiency causes Langer mesomelic dysplasia. ( 12116254 )
2002
12
Homozygous deletion of SHOX in a mentally retarded male with Langer mesomelic dysplasia. ( 11186941 )
2000
13
Two female siblings from Turkey with Langer mesomelic dysplasia (homozygous Leri-Weill dyschondrosteosis syndrome). ( 10770125 )
1999
14
Heterozygous manifestations of Langer mesomelic dysplasia. ( 3568430 )
1987

Variations for Langer Mesomelic Dysplasia

UniProtKB/Swiss-Prot genetic disease variations for Langer Mesomelic Dysplasia:

71
# Symbol AA change Variation ID SNP ID
1 SHOX p.Arg168Trp VAR_019416 rs137852557

ClinVar genetic disease variations for Langer Mesomelic Dysplasia:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 SHOX SHOX, DEL deletion Pathogenic
2 SHOX NM_000451.3(SHOX): c.517C> T (p.Arg173Cys) single nucleotide variant Pathogenic rs137852556 GRCh38 Chromosome X, 640851: 640851
3 SHOX NM_000451.3(SHOX): c.502C> T (p.Arg168Trp) single nucleotide variant Pathogenic rs137852557 GRCh38 Chromosome X, 640836: 640836
4 SHOX SHOX, 1-BP INS, 723C insertion Pathogenic
5 SHOX SHOX, 2-BP INS, 350AG insertion Pathogenic
6 SHOX SHOX, 1.1-MB DEL deletion Pathogenic
7 SHOX NM_000451.3(SHOX): c.508G> C (p.Ala170Pro) single nucleotide variant Pathogenic rs397514461 GRCh37 Chromosome X, 601577: 601577

Expression for Langer Mesomelic Dysplasia

Search GEO for disease gene expression data for Langer Mesomelic Dysplasia.

Pathways for Langer Mesomelic Dysplasia

GO Terms for Langer Mesomelic Dysplasia

Sources for Langer Mesomelic Dysplasia

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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