MCID: MND007
MIFTS: 51

Mandibuloacral Dysplasia

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

Aliases & Classifications for Mandibuloacral Dysplasia

MalaCards integrated aliases for Mandibuloacral Dysplasia:

Name: Mandibuloacral Dysplasia 54 50 24 25 56 29 13 52
Mandibuloacral Dysplasia with Type a Lipodystrophy 50 56 71
Mandibuloacral Dysostosis 25 29 69
Craniomandibular Dermatodysostosis 24 71
Mada 50 71
Mad 50 56
Lipodystrophy, Type a, Associated with Mandibuloacral Dysplasia 50
Lipodystrophy Type a Associated with Mandibuloacral Dysplasia 71
Mandibuloacral Dysplasia with Type a Lipodystrophy Atypical 71
Tendinous Calcinosis Arthropathy and Progeroid Features 71

Characteristics:

Orphanet epidemiological data:

56
mandibuloacral dysplasia
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: normal life expectancy;
mandibuloacral dysplasia with type a lipodystrophy
Inheritance: Autosomal recessive;

OMIM:

54
Inheritance:
autosomal recessive

Miscellaneous:
onset in childhood
genetic heterogeneity (see madb, )
allelic disorder to dunnigan-type familial partial lipodystrophy


HPO:

32
mandibuloacral dysplasia:
Inheritance heterogeneous autosomal recessive inheritance
Onset and clinical course juvenile onset


Classifications:



Summaries for Mandibuloacral Dysplasia

OMIM : 54
Mandibuloacral dysplasia with type A lipodystrophy (MADA) is an autosomal recessive disorder characterized by growth retardation, craniofacial anomalies with mandibular hypoplasia, skeletal abnormalities with progressive osteolysis of the distal phalanges and clavicles, and pigmentary skin changes. The lipodystrophy is characterized by a marked acral loss of fatty tissue with normal or increased fatty tissue in the neck and trunk. Some patients may show progeroid features. Metabolic complications can arise due to insulin resistance and diabetes (Young et al., 1971; Simha and Garg, 2002; summary by Garavelli et al., 2009). See also MAD type B (MADB; 608612), which is caused by mutation in the ZMPSTE24 gene (606480). (248370)

MalaCards based summary : Mandibuloacral Dysplasia, also known as mandibuloacral dysplasia with type a lipodystrophy, is related to hutchinson-gilford progeria and mandibuloacral dysplasia with type b lipodystrophy, and has symptoms including short stature, proptosis and wormian bones. An important gene associated with Mandibuloacral Dysplasia is LMNA (Lamin A/C), and among its related pathways/superpathways are Adipogenesis and Nuclear Envelope Reassembly. Affiliated tissues include skin, bone and tongue, and related phenotypes are behavior/neurological and integument

NIH Rare Diseases : 50 the following summary is from orphanet, a european reference portal for information on rare diseases and orphan drugs.orpha number: 2457disease definitionmandibuloacral dysplasia (mad) is a rare genetic bone disorder characterized by growth delay, postnatal development of craniofacial anomalies including mandibular hypoplasia, progressive acral osteolysis, mottled or patchy pigmentation, skin atrophy, and partial or generalized lipodystrophy.visit the orphanet disease page for more resources. last updated: 10/27/2015

UniProtKB/Swiss-Prot : 71 Mandibuloacral dysplasia with type A lipodystrophy: A disorder characterized by mandibular and clavicular hypoplasia, acroosteolysis, delayed closure of the cranial suture, progeroid appearance, partial alopecia, soft tissue calcinosis, joint contractures, and partial lipodystrophy with loss of subcutaneous fat from the extremities. Adipose tissue in the face, neck and trunk is normal or increased.

Genetics Home Reference : 25 Mandibuloacral dysplasia is a condition that causes a variety of abnormalities involving bone development, skin coloring (pigmentation), and fat distribution. People with this condition may grow slowly after birth. Most affected individuals are born with an underdeveloped lower jaw bone (mandible) and small collar bones (clavicles), leading to the characteristic features of a small chin and sloped shoulders. Other bone problems include loss of bone from the tips of the fingers (acroosteolysis), which causes bulbous finger tips; delayed closure of certain skull bones; and joint deformities (contractures).

Wikipedia : 72 Mandibuloacral dysplasia is a rare autosomal recessive syndrome characterized by mandibular hypoplasia,... more...

Related Diseases for Mandibuloacral Dysplasia

Graphical network of the top 20 diseases related to Mandibuloacral Dysplasia:



Diseases related to Mandibuloacral Dysplasia

Symptoms & Phenotypes for Mandibuloacral Dysplasia

Symptoms via clinical synopsis from OMIM:

54

Head And Neck- Mouth:
high-arched palate
absence of tongue papillae

Skeletal- Skull:
wormian bones
delayed closure of cranial sutures

Head And Neck- Eyes:
prominent eyes

Head And Neck- Teeth:
dental overcrowding
loss of teeth
hypoplastic teeth

Skeletal- Feet:
acroosteolysis of distal phalanges

Skin Nails & Hair- Skin:
mottled pigmentation
skin atrophy (especially over hands and feet)
soft tissue calcinosis

Muscle Soft Tissue:
loss of subcutaneous adipose tissue from extremities
normal or increased facial adipose tissue
normal or increased adipose tissue around the neck
partial lipodystrophy (abnormal distribution of adipose tissue)
normal or increased truncal adipose tissue
more
Laboratory- Abnormalities:
hyperglycemia
hyperlipidemia
hyperinsulinemia

Growth- Other:
growth retardation, postnatal

Skeletal:
joint contractures
joint stiffness

Head And Neck- Face:
mandibular hypoplasia
bird-like facies
full cheeks
normal or increased facial adipose tissue

Head And Neck- Nose:
pinched nose
pointed nose
beak nose

Chest- Ribs Sternum Clavicles And Scapulae:
clavicular hypoplasia
progressive acroosteolysis of the clavicle

Skeletal- Hands:
acroosteolysis of distal phalanges
fingertip rounding

Skin Nails & Hair- Hair:
alopecia, partial
sparse, lusterless scalp hair

Endocrine Features:
insulin-resistant diabetes mellitus
impaired glucose tolerance

Head And Neck- Neck:
normal or increased adipose tissue around the neck


Clinical features from OMIM:

248370

Human phenotypes related to Mandibuloacral Dysplasia:

56 32 (show top 50) (show all 71)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 short stature 56 32 hallmark (90%) Very frequent (99-80%) HP:0004322
2 proptosis 56 32 frequent (33%) Frequent (79-30%) HP:0000520
3 wormian bones 56 32 hallmark (90%) Very frequent (99-80%) HP:0002645
4 alopecia 56 32 frequent (33%) Very frequent (99-80%) HP:0001596
5 hyperlipidemia 56 32 frequent (33%) Frequent (79-30%) HP:0003077
6 large fontanelles 56 32 hallmark (90%) Very frequent (99-80%) HP:0000239
7 thin skin 56 32 hallmark (90%) Very frequent (99-80%) HP:0000963
8 cataract 56 32 occasional (7.5%) Occasional (29-5%) HP:0000518
9 absent eyelashes 56 32 occasional (7.5%) Occasional (29-5%) HP:0000561
10 high palate 56 32 hallmark (90%) Occasional (29-5%) HP:0000218
11 muscular hypotonia 56 32 occasional (7.5%) Occasional (29-5%) HP:0001252
12 insulin resistance 56 32 frequent (33%) Frequent (79-30%) HP:0000855
13 arthralgia 56 32 occasional (7.5%) Occasional (29-5%) HP:0002829
14 hearing impairment 56 32 occasional (7.5%) Occasional (29-5%) HP:0000365
15 breast aplasia 56 32 occasional (7.5%) Occasional (29-5%) HP:0100783
16 flexion contracture 56 32 occasional (7.5%) Occasional (29-5%) HP:0001371
17 lack of skin elasticity 56 32 occasional (7.5%) Occasional (29-5%) HP:0100679
18 limitation of joint mobility 56 32 hallmark (90%) Very frequent (99-80%) HP:0001376
19 abnormality of the eyebrow 56 32 frequent (33%) Frequent (79-30%) HP:0000534
20 short distal phalanx of finger 56 32 hallmark (90%) Very frequent (99-80%) HP:0009882
21 hyperpigmentation of the skin 56 32 occasional (7.5%) Occasional (29-5%) HP:0000953
22 aplasia/hypoplasia of the clavicles 56 32 hallmark (90%) Very frequent (99-80%) HP:0006710
23 progeroid facial appearance 56 32 hallmark (90%) Very frequent (99-80%) HP:0005328
24 dermal atrophy 56 32 hallmark (90%) Very frequent (99-80%) HP:0004334
25 osteolytic defects of the distal phalanges of the hand 56 32 frequent (33%) Very frequent (99-80%) HP:0009839
26 acroosteolysis of distal phalanges (feet) 56 32 frequent (33%) Very frequent (99-80%) HP:0001870
27 sparse scalp hair 32 HP:0002209
28 hypertriglyceridemia 32 frequent (33%) HP:0002155
29 hypercholesterolemia 32 frequent (33%) HP:0003124
30 micrognathia 32 hallmark (90%) HP:0000347
31 bird-like facies 32 HP:0000320
32 mottled pigmentation 32 HP:0001070
33 sparse hair 32 frequent (33%) HP:0008070
34 insulin-resistant diabetes mellitus 32 frequent (33%) HP:0000831
35 glucose intolerance 32 frequent (33%) HP:0000833
36 hyperglycemia 32 HP:0003074
37 hyperinsulinemia 32 hallmark (90%) HP:0000842
38 full cheeks 32 hallmark (90%) HP:0000293
39 narrow nasal ridge 32 HP:0000418
40 loss of subcutaneous adipose tissue in limbs 32 hallmark (90%) HP:0003635
41 increased intraabdominal fat 32 frequent (33%) HP:0008993
42 joint stiffness 32 HP:0001387
43 postnatal growth retardation 32 frequent (33%) HP:0008897
44 lipodystrophy 32 HP:0009125
45 acanthosis nigricans 32 frequent (33%) HP:0000956
46 narrow nose 32 hallmark (90%) HP:0000460
47 dental crowding 32 frequent (33%) HP:0000678
48 osteolysis 56 Very frequent (99-80%)
49 short clavicles 32 frequent (33%) HP:0000894
50 lipoatrophy 32 hallmark (90%) HP:0100578

UMLS symptoms related to Mandibuloacral Dysplasia:


joint stiffness

MGI Mouse Phenotypes related to Mandibuloacral Dysplasia:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.88 AGPAT2 BSCL2 LMNA MMP9 RCE1 ZMPSTE24
2 integument MP:0010771 9.8 AGPAT2 BSCL2 LMNA MMP9 RCE1 ZMPSTE24
3 digestive/alimentary MP:0005381 9.77 AGPAT2 BSCL2 LMNA MMP9 ZMPSTE24
4 adipose tissue MP:0005375 9.73 AGPAT2 BSCL2 LMNA ZMPSTE24
5 limbs/digits/tail MP:0005371 9.56 AGPAT2 LMNA MMP9 ZMPSTE24
6 liver/biliary system MP:0005370 9.55 AGPAT2 BSCL2 LMNA RCE1 ZMPSTE24
7 mortality/aging MP:0010768 9.5 AGPAT2 BSCL2 CBX1 LMNA MMP9 RCE1
8 renal/urinary system MP:0005367 9.02 AGPAT2 BSCL2 LMNA MMP9 ZMPSTE24

Drugs & Therapeutics for Mandibuloacral Dysplasia

Search Clinical Trials , NIH Clinical Center for Mandibuloacral Dysplasia

Genetic Tests for Mandibuloacral Dysplasia

Genetic tests related to Mandibuloacral Dysplasia:

id Genetic test Affiliating Genes
1 Mandibuloacral Dysplasia 29 24 ZMPSTE24 LMNA
2 Mandibuloacral Dysostosis 29

Anatomical Context for Mandibuloacral Dysplasia

MalaCards organs/tissues related to Mandibuloacral Dysplasia:

39
Skin, Bone, Tongue, Eye, Breast

Publications for Mandibuloacral Dysplasia

Articles related to Mandibuloacral Dysplasia:

(show top 50) (show all 51)
id Title Authors Year
1
Mandibuloacral dysplasia and LMNA A529V mutation in Turkish patients with severe skeletal changes and absent breast development. ( 27100822 )
2016
2
Failure of ossification of the occipital bone in mandibuloacral dysplasia type B. ( 27410998 )
2016
3
A novel homozygous LMNA mutation (p.Met540Ile) causes mandibuloacral dysplasia type A. ( 26602028 )
2016
4
Mandibuloacral Dysplasia Type B in an Infant: A Rare Progeroid Genodermatosis. ( 25629449 )
2015
5
Hutchinson-gilford progeria versus mandibuloacral dysplasia. ( 24700965 )
2014
6
Mandibuloacral Dysplasia Caused by LMNA Mutations and Uniparental Disomy. ( 24639906 )
2014
7
Mandibuloacral dysplasia. ( 24793088 )
2014
8
Rapamycin treatment of Mandibuloacral Dysplasia cells rescues localization of chromatin-associated proteins and cell cycle dynamics. ( 25324471 )
2014
9
Mandibuloacral dysplasia type A-associated progeria caused by homozygous LMNA mutation in a family from Southern China. ( 25286833 )
2014
10
Ultrastructural skin changes in Egyptian mandibuloacral dysplasia patients with p.Arg527Leu LMNA mutation and in their asymptomatic heterozygotic mothers. ( 23775434 )
2013
11
Precautions in using a perforator free flap to treat mandibuloacral dysplasia-a case report. ( 24123119 )
2013
12
A novel homozygous p.Arg527Leu LMNA mutation in two unrelated Egyptian families causes overlapping mandibuloacral dysplasia and progeria syndrome. ( 22549407 )
2012
13
Altered chromatin organization and SUN2 localization in mandibuloacral dysplasia are rescued by drug treatment. ( 22706480 )
2012
14
Familial partial lipodystrophy, mandibuloacral dysplasia and restrictive dermopathy feature barrier-to-autointegration factor (BAF) nuclear redistribution. ( 22935701 )
2012
15
Type B mandibuloacral dysplasia with congenital myopathy due to homozygous ZMPSTE24 missense mutation. ( 21267004 )
2011
16
Osteoblasts from a mandibuloacral dysplasia patient induce human blood precursors to differentiate into active osteoclasts. ( 21419220 )
2011
17
Elbow deformities in a patient with mandibuloacral dysplasia type A. ( 20949529 )
2010
18
Skeletal phenotype of mandibuloacral dysplasia associated with mutations in ZMPSTE24. ( 20550970 )
2010
19
Early onset mandibuloacral dysplasia due to compound heterozygous mutations in ZMPSTE24. ( 20814950 )
2010
20
Mandibuloacral dysplasia type A in childhood. ( 19764019 )
2009
21
Increased release and activity of matrix metalloproteinase-9 in patients with mandibuloacral dysplasia type A, a rare premature ageing syndrome. ( 18554282 )
2008
22
Association of homozygous LMNA mutation R471C with new phenotype: mandibuloacral dysplasia, progeria, and rigid spine muscular dystrophy. ( 18348272 )
2008
23
Severe mandibuloacral dysplasia caused by novel compound heterozygous ZMPSTE24 mutations in two Japanese siblings. ( 18435794 )
2008
24
Severe mandibuloacral dysplasia-associated lipodystrophy and progeria in a young girl with a novel homozygous Arg527Cys LMNA mutation. ( 18796515 )
2008
25
Compound heterozygosity for mutations in LMNA in a patient with a myopathic and lipodystrophic mandibuloacral dysplasia type A phenotype. ( 17848409 )
2007
26
Mandibuloacral dysplasia and a novel LMNA mutation in a woman with severe progressive skeletal changes. ( 17935239 )
2007
27
Focal segmental glomerulosclerosis in patients with mandibuloacral dysplasia owing to ZMPSTE24 deficiency. ( 17152860 )
2006
28
A novel homozygous Ala529Val LMNA mutation in Turkish patients with mandibuloacral dysplasia. ( 15998779 )
2005
29
Mandibuloacral dysplasia: a report of two Egyptian cases. ( 16440877 )
2005
30
Alterations of nuclear envelope and chromatin organization in mandibuloacral dysplasia, a rare form of laminopathy. ( 16046620 )
2005
31
Gene expression profiling of fibroblasts from a human progeroid disease (mandibuloacral dysplasia, MAD #248370) through cDNA microarrays. ( 15473259 )
2004
32
A case of mandibuloacral dysplasia presenting with features of scleroderma. ( 15311567 )
2004
33
Mandibuloacral dysplasia caused by homozygosity for the R527H mutation in lamin A/C. ( 14627682 )
2003
34
Genetic and phenotypic heterogeneity in patients with mandibuloacral dysplasia-associated lipodystrophy. ( 12788894 )
2003
35
Zinc metalloproteinase, ZMPSTE24, is mutated in mandibuloacral dysplasia. ( 12913070 )
2003
36
Mandibuloacral dysplasia with absent breast development. ( 12784312 )
2003
37
Body fat distribution and metabolic derangements in patients with familial partial lipodystrophy associated with mandibuloacral dysplasia. ( 11836320 )
2002
38
Mandibuloacral dysplasia is caused by a mutation in LMNA-encoding lamin A/C. ( 12075506 )
2002
39
Familial mandibuloacral dysplasia: report of an additional Italian patient. ( 10995511 )
2000
40
Premature adrenal cortical dysfunction in mandibuloacral dysplasia: a progeroid-like syndrome. ( 11102943 )
2000
41
Familial mandibuloacral dysplasia--a report of four cases. ( 9732012 )
1998
42
Lethal neonatal mandibuloacral dysplasia. ( 8957511 )
1996
43
Long-term follow-up of cutaneous changes in siblings with mandibuloacral dysplasia who were originally considered to have hereditary sclerosing poikiloderma. ( 7593806 )
1995
44
Severe insulin resistance and diabetes mellitus in mandibuloacral dysplasia. ( 1736653 )
1992
45
A severe case of mandibuloacral dysplasia in a girl. ( 1642279 )
1992
46
Mandibuloacral dysplasia as a form of idiopathic osteolysis. ( 1815190 )
1991
47
Insulin-resistant diabetes mellitus and hypermetabolism in mandibuloacral dysplasia: a newly recognized form of partial lipodystrophy. ( 1939519 )
1991
48
Another Italian family with mandibuloacral dysplasia: why does it seem more frequent in Italy? ( 3717214 )
1986
49
Mandibuloacral dysplasia: a rare progeroid syndrome. Two brothers confirm autosomal recessive inheritance. ( 6467666 )
1984
50
Familial mandibuloacral dysplasia. ( 7317281 )
1981

Variations for Mandibuloacral Dysplasia

UniProtKB/Swiss-Prot genetic disease variations for Mandibuloacral Dysplasia:

71
id Symbol AA change Variation ID SNP ID
1 LMNA p.Arg527His VAR_018727 rs57520892
2 LMNA p.Ala529Val VAR_034709 rs60580541
3 LMNA p.Ser573Leu VAR_039789 rs60890628

ClinVar genetic disease variations for Mandibuloacral Dysplasia:

6 (show all 11)
id Gene Variation Type Significance SNP ID Assembly Location
1 LMNA NM_170707.3(LMNA): c.1579C> T (p.Arg527Cys) single nucleotide variant Pathogenic rs57318642 GRCh37 Chromosome 1, 156106994: 156106994
2 LMNA NM_170707.3(LMNA): c.1824C> T (p.Gly608=) single nucleotide variant Pathogenic rs58596362 GRCh37 Chromosome 1, 156108404: 156108404
3 LMNA NM_170707.3(LMNA): c.1411C> T (p.Arg471Cys) single nucleotide variant Pathogenic rs28928902 GRCh37 Chromosome 1, 156106742: 156106742
4 LMNA NM_170707.3(LMNA): c.1626G> C (p.Lys542Asn) single nucleotide variant Pathogenic rs56673169 GRCh37 Chromosome 1, 156107462: 156107462
5 LMNA NM_170707.3(LMNA): c.1586C> T (p.Ala529Val) single nucleotide variant Pathogenic rs60580541 GRCh37 Chromosome 1, 156107001: 156107001
6 LMNA NM_170707.3(LMNA): c.1318G> A (p.Val440Met) single nucleotide variant Pathogenic rs121912493 GRCh37 Chromosome 1, 156106165: 156106165
7 LMNA NM_170707.3(LMNA): c.1585G> A (p.Ala529Thr) single nucleotide variant Pathogenic rs121912494 GRCh37 Chromosome 1, 156107000: 156107000
8 LMNA NM_170707.3(LMNA): c.1072G> A (p.Glu358Lys) single nucleotide variant Pathogenic rs60458016 GRCh37 Chromosome 1, 156105827: 156105827
9 LMNA NM_170707.3(LMNA): c.1488+1G> A single nucleotide variant Pathogenic rs267607640 GRCh37 Chromosome 1, 156106820: 156106820
10 LMNA NM_170707.3(LMNA): c.1583C> A (p.Thr528Lys) single nucleotide variant Pathogenic/Likely pathogenic rs57629361 GRCh37 Chromosome 1, 156106998: 156106998
11 LMNA NM_170707.3(LMNA): c.1620G> A (p.Met540Ile) single nucleotide variant Pathogenic rs483352811 GRCh37 Chromosome 1, 156107456: 156107456

Expression for Mandibuloacral Dysplasia

Search GEO for disease gene expression data for Mandibuloacral Dysplasia.

Pathways for Mandibuloacral Dysplasia

Pathways related to Mandibuloacral Dysplasia according to GeneCards Suite gene sharing:

id Super pathways Score Top Affiliating Genes
1 11.04 AGPAT2 BSCL2 LMNA ZMPSTE24
2
Show member pathways
10.47 BANF1 LMNA

GO Terms for Mandibuloacral Dysplasia

Cellular components related to Mandibuloacral Dysplasia according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 endoplasmic reticulum membrane GO:0005789 9.26 AGPAT2 BSCL2 RCE1 ZMPSTE24
2 integral component of endoplasmic reticulum membrane GO:0030176 8.8 BSCL2 RCE1 ZMPSTE24

Biological processes related to Mandibuloacral Dysplasia according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 mitotic nuclear envelope disassembly GO:0007077 9.26 BANF1 LMNA
2 nuclear envelope organization GO:0006998 9.16 LMNA ZMPSTE24
3 mitotic nuclear envelope reassembly GO:0007084 8.96 BANF1 LMNA
4 CAAX-box protein processing GO:0071586 8.62 RCE1 ZMPSTE24

Molecular functions related to Mandibuloacral Dysplasia according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 endopeptidase activity GO:0004175 8.96 MMP9 RCE1
2 metalloendopeptidase activity GO:0004222 8.8 MMP9 RCE1 ZMPSTE24

Sources for Mandibuloacral Dysplasia

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7 CNVD
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10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
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30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
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42 MeSH
43 MESH via Orphanet
44 MGI
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55 OMIM via Orphanet
59 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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