MCID: LNG040
MIFTS: 33

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 57 53 25 59 75 13 55
Lmd 57 25 75
Mesomelic Dwarfism of the Hypoplastic Ulna, Fibula, and Mandible Type 57 25
Langer Mesomelic Dysplasia Syndrome 29 6
Dyschondrosteosis, Homozygous 57 53
Mesomelic Dwarfism of the Hypoplastic Ulna, Fibula and Mandible Type 53
Mesomelic Dwarfism, Langer Type 59
Dyschondrosteosis Homozygous 25
Dysplasia, Mesomelic, Langer 40
Langer Mesomelic Dwarfism 25

Characteristics:

Orphanet epidemiological data:

59
langer mesomelic dysplasia
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: normal life expectancy;

OMIM:

57
Inheritance:
autosomal recessive

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


HPO:

32
langer mesomelic dysplasia:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 57 249700
Orphanet 59 ORPHA2632
ICD10 via Orphanet 34 Q87.1
MESH via Orphanet 45 C537267
UMLS via Orphanet 74 C0432230
MedGen 42 C0432230

Summaries for Langer Mesomelic Dysplasia

NIH Rare Diseases : 53 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.

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

Genetics Home Reference : 25 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 : 57 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 : 75 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 : 76 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 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 autism 5.6 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:

57
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:

59 32 (show all 23)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 high palate 59 32 hallmark (90%) Very frequent (99-80%) HP:0000218
2 abnormality of the carpal bones 59 32 hallmark (90%) Very frequent (99-80%) HP:0001191
3 micromelia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002983
4 abnormality of the ulna 59 32 hallmark (90%) Very frequent (99-80%) HP:0002997
5 madelung deformity 59 32 hallmark (90%) Very frequent (99-80%) HP:0003067
6 severe short stature 59 32 hallmark (90%) Very frequent (99-80%) HP:0003510
7 mesomelic/rhizomelic limb shortening 59 32 hallmark (90%) Very frequent (99-80%) HP:0005026
8 abnormality of epiphysis morphology 59 32 hallmark (90%) Very frequent (99-80%) HP:0005930
9 bowing of the long bones 59 32 hallmark (90%) Very frequent (99-80%) HP:0006487
10 aplasia/hypoplasia of the fibula 59 32 hallmark (90%) Very frequent (99-80%) HP:0006492
11 ulnar deviation of finger 59 32 hallmark (90%) Very frequent (99-80%) HP:0009465
12 short femoral neck 59 32 hallmark (90%) Very frequent (99-80%) HP:0100864
13 disproportionate short-limb short stature 59 Very frequent (99-80%)
14 micrognathia 32 HP:0000347
15 lumbar hyperlordosis 32 HP:0002938
16 hypoplasia of the radius 32 HP:0002984
17 radial bowing 32 HP:0002986
18 hypoplasia of the ulna 32 HP:0003022
19 mesomelia 32 HP:0003027
20 broad ulna 32 HP:0003993
21 rudimentary fibula 32 HP:0006381
22 shortening of the tibia 32 HP:0006436
23 mesomelic short stature 32 HP:0008845

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 29 SHOX

Anatomical Context for Langer Mesomelic Dysplasia

MalaCards organs/tissues related to Langer Mesomelic Dysplasia:

41
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
Identification of a Gypsy SHOX mutation (p.A170P) in LAcri-Weill dyschondrosteosis and Langer mesomelic dysplasia. ( 21712857 )
2011
5
First-trimester ultrasonographic diagnosis of Langer mesomelic dysplasia in a previously affected family. ( 21692083 )
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
Complete SHOX deficiency causes Langer mesomelic dysplasia. ( 12116254 )
2002
11
Pseudodominant inheritance of Langer mesomelic dysplasia caused by a SHOX homeobox missense mutation. ( 12116253 )
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:

75
# Symbol AA change Variation ID SNP ID
1 SHOX p.Arg168Trp VAR_019416 rs137852557

ClinVar genetic disease variations for Langer Mesomelic Dysplasia:

6
(show all 16)
# 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 GRCh37 Chromosome X, 601586: 601586
3 SHOX NM_000451.3(SHOX): c.517C> T (p.Arg173Cys) single nucleotide variant Pathogenic rs137852556 GRCh38 Chromosome X, 640851: 640851
4 SHOX NM_000451.3(SHOX): c.517C> T (p.Arg173Cys) single nucleotide variant Pathogenic rs137852556 GRCh38 Chromosome Y, 640851: 640851
5 SHOX NM_000451.3(SHOX): c.517C> T (p.Arg173Cys) single nucleotide variant Pathogenic rs137852556 GRCh37 Chromosome Y, 551586: 551586
6 SHOX NM_000451.3(SHOX): c.502C> T (p.Arg168Trp) single nucleotide variant Pathogenic rs137852557 GRCh38 Chromosome X, 640836: 640836
7 SHOX NM_000451.3(SHOX): c.502C> T (p.Arg168Trp) single nucleotide variant Pathogenic rs137852557 GRCh37 Chromosome X, 601571: 601571
8 SHOX NM_000451.3(SHOX): c.502C> T (p.Arg168Trp) single nucleotide variant Pathogenic rs137852557 GRCh37 Chromosome Y, 551571: 551571
9 SHOX NM_000451.3(SHOX): c.502C> T (p.Arg168Trp) single nucleotide variant Pathogenic rs137852557 GRCh38 Chromosome Y, 640836: 640836
10 SHOX SHOX, 1-BP INS, 723C insertion Pathogenic
11 SHOX SHOX, 2-BP INS, 350AG insertion Pathogenic
12 SHOX SHOX, 1.1-MB DEL deletion Pathogenic
13 SHOX NM_000451.3(SHOX): c.508G> C (p.Ala170Pro) single nucleotide variant Pathogenic rs397514461 GRCh37 Chromosome X, 601577: 601577
14 SHOX NM_000451.3(SHOX): c.508G> C (p.Ala170Pro) single nucleotide variant Pathogenic rs397514461 GRCh38 Chromosome X, 640842: 640842
15 SHOX NM_000451.3(SHOX): c.508G> C (p.Ala170Pro) single nucleotide variant Pathogenic rs397514461 GRCh38 Chromosome Y, 640842: 640842
16 SHOX NM_000451.3(SHOX): c.508G> C (p.Ala170Pro) single nucleotide variant Pathogenic rs397514461 GRCh37 Chromosome Y, 551577: 551577

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
17 ExPASy
19 FMA
28 GO
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30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
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44 MeSH
45 MESH via Orphanet
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49 NCI
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54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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