MAD
MCID: MND007
MIFTS: 61

Mandibuloacral Dysplasia (MAD) malady

Genetic diseases, Rare diseases, Bone diseases, Skin diseases, Endocrine diseases, Fetal diseases categories
Download this MalaCard

Summaries for Mandibuloacral Dysplasia

About this section


Fully expand this MalaCard
Genetics Home Reference:21 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).

MalaCards based summary: Mandibuloacral Dysplasia, also known as mandibuloacral dysplasia with type a lipodystrophy, is related to progeria and lipodystrophy, and has symptoms including large fontanelle/delayed fontanelle closure, wormian bones and abnormal dentition/dental position/implantation/unerupted/dental ankylosis. An important gene associated with Mandibuloacral Dysplasia is LMNA (lamin A/C), and among its related pathways are Nuclear Envelope Reassembly and Celecoxib Pathway, Pharmacodynamics. The compounds hydroxamate and 1,10-phenanthroline have been mentioned in the context of this disorder. Affiliated tissues include skin, bone and breast, and related mouse phenotypes are limbs/digits/tail and vision/eye.

Wikipedia:65 Mandibuloacral dysplasia is a rare autosomal recessive syndrome characterized by mandibular hypoplasia,... more...

Description from OMIM:46 248370

Aliases & Classifications for Mandibuloacral Dysplasia

About this section
Sources:
42NIH Rare Diseases, 20GeneTests, 22GTR, 21Genetics Home Reference, 46OMIM, 44Novoseek, 48Orphanet, 62UMLS, 35MESH via Orphanet, 26ICD10 via Orphanet
See all sources

Mandibuloacral Dysplasia, Aliases & Descriptions:

Name: Mandibuloacral Dysplasia 42 20 22 21 46 44
Mandibuloacral Dysplasia with Type a Lipodystrophy 48 62
 
Mandibuloacral Dysostosis 21 62
Mad 42


Classifications:



Characteristics (Orphanet epidemiological data):

48
mandibuloacral dysplasia with type a lipodystrophy:
Inheritance: Autosomal recessive


External Ids:

OMIM46 248370
MESH via Orphanet35 C535705
ICD10 via Orphanet26 Q87.5

Related Diseases for Mandibuloacral Dysplasia

About this section

Diseases related to Mandibuloacral Dysplasia via text searches within MalaCards or GeneCards/GeneDecks gene sharing:

(show all 38)
idRelated DiseaseScoreTop Affiliating Genes
1progeria30.9BANF1, RCE1, LMNA, ZMPSTE24
2lipodystrophy29.9AGPAT2, ZMPSTE24, LMNA, INS, BSCL2, PPARG
3familial partial lipodystrophy29.8BSCL2, PPARG, INS, LMNA, AGPAT2
4insulin resistance29.8BSCL2, INS, LMNA, AGPAT2, PPARG
5diabetes mellitus29.6PPARG, BSCL2, INS, LMNA, MMP9
6mandibuloacral dysplasia with type b lipodystrophy10.6
7mandibuloacral dysplasia with type a lipodystrophy10.5
8distal hereditary motor neuropathy10.4AGPAT2
9tight skin contracture syndrome, lethal10.4ZMPSTE24, LMNA
10morbid obesity10.3INS
11emery-dreifuss muscular dystrophy10.3LMNA, BANF1
12berardinelli-seip congenital lipodystrophy10.3BSCL2, AGPAT2
13focal segmental glomerulosclerosis10.2
14cleidocranial dysplasia10.2
15glomerulosclerosis10.2
16muscular dystrophy10.2
17myopathy10.2
18scleroderma10.2
19prediabetes syndrome10.0PPARG, INS
20idiopathic edema10.0PPARG, INS
21hyperinsulinism9.9PPARG, INS
22fatty liver disease9.9INS, PPARG
23hyperandrogenism9.9PPARG, INS, LMNA
24acanthosis nigricans9.9BSCL2, INS, LMNA, AGPAT2
25polycystic ovary syndrome9.9LMNA, INS, PPARG
26glucose intolerance9.9PPARG, INS
27stroke, ischemic9.8INS, MMP9
28metabolic syndrome x9.8LMNA, INS, PPARG
29hypertriglyceridemia9.8BSCL2, INS, PPARG
30type 2 diabetes mellitus9.8INS, PPARG, LMNA
31congenital heart disease9.7MMP9, PPARG, INS
32hypertension9.7PPARG, INS, MMP9
33obesity9.7LMNA, PPARG, INS
34vascular disease9.7MMP9, INS, PPARG
35coronary artery anomaly9.6MMP9, LMNA, PPARG, INS
36pancreatic cancer9.6INS, PPARG, MMP9
37atherosclerosis9.6PPARG, MMP9, LMNA, INS
38congenital generalized lipodystrophy type 29.4AGPAT2, PPARG, BSCL2, INS, LMNA, ZMPSTE24

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



Diseases related to mandibuloacral dysplasia

Symptoms for Mandibuloacral Dysplasia

About this section

Symptoms by clinical synopsis from OMIM:

248370

Clinical features from OMIM:

248370

Symptoms:

48 (show all 28)
  • large fontanelle/delayed fontanelle closure
  • wormian bones
  • abnormal dentition/dental position/implantation/unerupted/dental ankylosis
  • clavicle absent/abnormal
  • terminal/third phalangeal bone of fingers hypoplasia
  • skin hypoplasia/aplasia/atrophy
  • alopecia
  • osteolysis/osteoclasia/bone destruction/erosions
  • restricted joint mobility/joint stiffness/ankylosis
  • short stature/dwarfism/nanism
  • premature ageing
  • proptosis/exophthalmos
  • eyebrows anomalies
  • insulin resistance
  • hyperlipidemia/hypercholesterolemia/hypertriglyceridemia
  • cataract/lens opacification
  • anomalies of eyelids, eyelashes and lacrimal system
  • high vaulted/narrow palate
  • anomalies of teeth and dentition
  • hearing loss/hypoacusia/deafness
  • breast tissue/mammary gland absence/aplasia
  • tight skin/lack of elasticity
  • abnormal pigmentary skin changes/skin pigmentation anomalies
  • hypotonia
  • muscle anomalies
  • anomalies of cartilages, joints and periarticular tissue
  • articular/joint pain/arthralgia
  • autosomal recessive inheritance

HPO human phenotypes related to Mandibuloacral Dysplasia:

(show all 59)
id Description Frequency HPO Source Accession
1 abnormality of the teeth hallmark (90%) HP:0000164
2 abnormality of the clavicles hallmark (90%) HP:0000889
3 limitation of joint mobility hallmark (90%) HP:0001376
4 alopecia hallmark (90%) HP:0001596
5 wormian bones hallmark (90%) HP:0002645
6 osteolysis hallmark (90%) HP:0002797
7 short stature hallmark (90%) HP:0004322
8 prematurely aged appearance hallmark (90%) HP:0007495
9 aplasia/hypoplasia of the skin hallmark (90%) HP:0008065
10 short distal phalanx of finger hallmark (90%) HP:0009882
11 proptosis typical (50%) HP:0000520
12 abnormality of the eyebrow typical (50%) HP:0000534
13 insulin resistance typical (50%) HP:0000855
14 abnormality of lipid metabolism typical (50%) HP:0003119
15 abnormality of the teeth occasional (7.5%) HP:0000164
16 abnormality of the palate occasional (7.5%) HP:0000174
17 hearing impairment occasional (7.5%) HP:0000365
18 cataract occasional (7.5%) HP:0000518
19 abnormality of skin pigmentation occasional (7.5%) HP:0001000
20 muscular hypotonia occasional (7.5%) HP:0001252
21 arthralgia occasional (7.5%) HP:0002829
22 lack of skin elasticity occasional (7.5%) HP:0100679
23 breast aplasia occasional (7.5%) HP:0100783
24 autosomal recessive inheritance HP:0000007
25 high palate HP:0000218
26 delayed cranial suture closure HP:0000270
27 increased facial adipose tissue HP:0000287
28 full cheeks HP:0000293
29 bird-like facies HP:0000320
30 micrognathia HP:0000347
31 narrow nasal ridge HP:0000418
32 increased adipose tissue around the neck HP:0000468
33 proptosis HP:0000520
34 dental crowding HP:0000678
35 hypoplasia of teeth HP:0000685
36 insulin-resistant diabetes mellitus HP:0000831
37 glucose intolerance HP:0000833
38 hyperinsulinemia HP:0000842
39 short clavicles HP:0000894
40 progressive clavicular acroosteolysis HP:0000905
41 decreased subcutaneous fat HP:0001002
42 mottled pigmentation HP:0001070
43 flexion contracture HP:0001371
44 joint stiffness HP:0001387
45 heterogeneous HP:0001425
46 alopecia HP:0001596
47 acroosteolysis of distal phalanges (feet) HP:0001870
48 sparse scalp hair HP:0002209
49 wormian bones HP:0002645
50 hyperglycemia HP:0003074
51 hyperlipidemia HP:0003077
52 juvenile onset HP:0003621
53 loss of subcutaneous adipose tissue in limbs HP:0003635
54 calcinosis HP:0003761
55 dermal atrophy HP:0004334
56 premature loss of teeth HP:0006480
57 postnatal growth retardation HP:0008897
58 lipodystrophy HP:0009125
59 osteolytic defects of the distal phalanges of the hand HP:0009839

Drugs & Therapeutics for Mandibuloacral Dysplasia

About this section

Drug clinical trials:

Search ClinicalTrials for Mandibuloacral Dysplasia

Search NIH Clinical Center for Mandibuloacral Dysplasia

Genetic Tests for Mandibuloacral Dysplasia

About this section

Genetic tests related to Mandibuloacral Dysplasia:

id Genetic test Affiliating Genes
1 Mandibuloacral Dysplasia20 22 ZMPSTE24

Anatomical Context for Mandibuloacral Dysplasia

About this section

MalaCards organs/tissues related to Mandibuloacral Dysplasia:

32
Skin, Bone, Breast

Animal Models for Mandibuloacral Dysplasia or affiliated genes

About this section

Publications for Mandibuloacral Dysplasia

About this section

Articles related to Mandibuloacral Dysplasia:

(show all 47)
idTitleAuthorsYear
1
Mandibuloacral Dysplasia Caused by LMNA Mutations and Uniparental Disomy. (24639906)
2014
2
Hutchinson-gilford progeria versus mandibuloacral dysplasia. (24700965)
2014
3
Mandibuloacral dysplasia type A-associated progeria caused by homozygous LMNA mutation in a family from Southern China. (25286833)
2014
4
Mandibuloacral dysplasia. (24793088)
2014
5
Rapamycin treatment of Mandibuloacral Dysplasia cells rescues localization of chromatin-associated proteins and cell cycle dynamics. (25324471)
2014
6
Precautions in using a perforator free flap to treat mandibuloacral dysplasia-a case report. (24123119)
2013
7
Ultrastructural skin changes in Egyptian mandibuloacral dysplasia patients with p.Arg527Leu LMNA mutation and in their asymptomatic heterozygotic mothers. (23775434)
2013
8
A novel homozygous p.Arg527Leu LMNA mutation in two unrelated Egyptian families causes overlapping mandibuloacral dysplasia and progeria syndrome. (22549407)
2012
9
Altered chromatin organization and SUN2 localization in mandibuloacral dysplasia are rescued by drug treatment. (22706480)
2012
10
Familial partial lipodystrophy, mandibuloacral dysplasia and restrictive dermopathy feature barrier-to-autointegration factor (BAF) nuclear redistribution. (22935701)
2012
11
Osteoblasts from a mandibuloacral dysplasia patient induce human blood precursors to differentiate into active osteoclasts. (21419220)
2011
12
Type B mandibuloacral dysplasia with congenital myopathy due to homozygous ZMPSTE24 missense mutation. (21267004)
2011
13
Early onset mandibuloacral dysplasia due to compound heterozygous mutations in ZMPSTE24. (20814950)
2010
14
Elbow deformities in a patient with mandibuloacral dysplasia type A. (20949529)
2010
15
Skeletal phenotype of mandibuloacral dysplasia associated with mutations in ZMPSTE24. (20550970)
2010
16
Mandibuloacral dysplasia type A in childhood. (19764019)
2009
17
Severe mandibuloacral dysplasia-associated lipodystrophy and progeria in a young girl with a novel homozygous Arg527Cys LMNA mutation. (18796515)
2008
18
Severe mandibuloacral dysplasia caused by novel compound heterozygous ZMPSTE24 mutations in two Japanese siblings. (18435794)
2008
19
Association of homozygous LMNA mutation R471C with new phenotype: mandibuloacral dysplasia, progeria, and rigid spine muscular dystrophy. (18348272)
2008
20
Increased release and activity of matrix metalloproteinase-9 in patients with mandibuloacral dysplasia type A, a rare premature ageing syndrome. (18554282)
2008
21
Mandibuloacral dysplasia and a novel LMNA mutation in a woman with severe progressive skeletal changes. (17935239)
2007
22
Compound heterozygosity for mutations in LMNA in a patient with a myopathic and lipodystrophic mandibuloacral dysplasia type A phenotype. (17848409)
2007
23
Focal segmental glomerulosclerosis in patients with mandibuloacral dysplasia owing to ZMPSTE24 deficiency. (17152860)
2006
24
A novel homozygous Ala529Val LMNA mutation in Turkish patients with mandibuloacral dysplasia. (15998779)
2005
25
Alterations of nuclear envelope and chromatin organization in mandibuloacral dysplasia, a rare form of laminopathy. (16046620)
2005
26
Mandibuloacral dysplasia: a report of two Egyptian cases. (16440877)
2005
27
A case of mandibuloacral dysplasia presenting with features of scleroderma. (15311567)
2004
28
Gene expression profiling of fibroblasts from a human progeroid disease (mandibuloacral dysplasia, MAD #248370) through cDNA microarrays. (15473259)
2004
29
Zinc metalloproteinase, ZMPSTE24, is mutated in mandibuloacral dysplasia. (12913070)
2003
30
Mandibuloacral dysplasia with absent breast development. (12784312)
2003
31
Genetic and phenotypic heterogeneity in patients with mandibuloacral dysplasia-associated lipodystrophy. (12788894)
2003
32
Mandibuloacral dysplasia caused by homozygosity for the R527H mutation in lamin A/C. (14627682)
2003
33
Body fat distribution and metabolic derangements in patients with familial partial lipodystrophy associated with mandibuloacral dysplasia. (11836320)
2002
34
Mandibuloacral dysplasia is caused by a mutation in LMNA-encoding lamin A/C. (12075506)
2002
35
Premature adrenal cortical dysfunction in mandibuloacral dysplasia: a progeroid-like syndrome. (11102943)
2000
36
Familial mandibuloacral dysplasia: report of an additional Italian patient. (10995511)
2000
37
Familial mandibuloacral dysplasia--a report of four cases. (9732012)
1998
38
Lethal neonatal mandibuloacral dysplasia. (8957511)
1996
39
Long-term follow-up of cutaneous changes in siblings with mandibuloacral dysplasia who were originally considered to have hereditary sclerosing poikiloderma. (7593806)
1995
40
Severe insulin resistance and diabetes mellitus in mandibuloacral dysplasia. (1736653)
1992
41
A severe case of mandibuloacral dysplasia in a girl. (1642279)
1992
42
Insulin-resistant diabetes mellitus and hypermetabolism in mandibuloacral dysplasia: a newly recognized form of partial lipodystrophy. (1939519)
1991
43
Mandibuloacral dysplasia as a form of idiopathic osteolysis. (1815190)
1991
44
Another Italian family with mandibuloacral dysplasia: why does it seem more frequent in Italy? (3717214)
1986
45
Mandibuloacral dysplasia: a rare progeroid syndrome. Two brothers confirm autosomal recessive inheritance. (6467666)
1984
46
Familial mandibuloacral dysplasia. (7317281)
1981
47
New syndrome manifested by mandibular hypoplasia, acroosteolysis, stiff joints and cutaneous atrophy (mandibuloacral dysplasia) in two unrelated boys. (5173234)
1971

Variations for Mandibuloacral Dysplasia

About this section

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

64
id Symbol AA change Variation ID SNP ID
1LMNAp.Arg527HisVAR_018727
2LMNAp.Ala529ValVAR_034709
3LMNAp.Ser573LeuVAR_039789

Clinvar genetic disease variations for Mandibuloacral Dysplasia:

6
id Gene Name Type Significance SNP ID Assembly Location
1LMNANM_005572.3(LMNA): c.1620G> A (p.Met540Ile)single nucleotide variantLikely pathogenicrs483352811GRCh37Chr 1, 156107456: 156107456
2LMNANM_005572.3(LMNA): c.1579C> T (p.Arg527Cys)single nucleotide variantPathogenicrs57318642GRCh37Chr 1, 156106994: 156106994
3LMNANM_005572.3(LMNA): c.1580G> A (p.Arg527His)single nucleotide variantPathogenicrs57520892GRCh37Chr 1, 156106995: 156106995
4LMNANM_005572.3(LMNA): c.1626G> C (p.Lys542Asn)single nucleotide variantPathogenicrs56673169GRCh37Chr 1, 156107462: 156107462
5LMNANM_005572.3(LMNA): c.1586C> T (p.Ala529Val)single nucleotide variantPathogenicrs60580541GRCh37Chr 1, 156107001: 156107001
6LMNANM_005572.3(LMNA): c.1585G> A (p.Ala529Thr)single nucleotide variantPathogenicrs121912494GRCh37Chr 1, 156107000: 156107000

Expression for genes affiliated with Mandibuloacral Dysplasia

About this section
Expression patterns in normal tissues for genes affiliated with Mandibuloacral Dysplasia

Search GEO for disease gene expression data for Mandibuloacral Dysplasia.

Pathways for genes affiliated with Mandibuloacral Dysplasia

About this section

Pathways related to Mandibuloacral Dysplasia according to GeneCards/GeneDecks:

idSuper pathways (with members indented)ScoreTop Affiliating Genes
1
Show member pathways
9.8LMNA, BANF1
29.5MMP9, PPARG
39.4MMP9, INS
4
Show member pathways
Cholesterol biosynthesis37
lanosterol biosynthesis37
zymosterol biosynthesis37
mevalonate pathway I37
epoxysqualene biosynthesis37
cholesterol biosynthesis II (via 24,25-dihydrolanosterol)37
superpathway of geranylgeranyldiphosphate biosynthesis I (via mevalonate)37
trans, trans-farnesyl diphosphate biosynthesis37
cholesterol biosynthesis I37
cholesterol biosynthesis III (via desmosterol)37
geranylgeranyldiphosphate biosynthesis37
9.3RCE1, ZMPSTE24
57.9AGPAT2, ZMPSTE24, LMNA, INS, BSCL2, PPARG

Compounds for genes affiliated with Mandibuloacral Dysplasia

About this section

Compounds related to Mandibuloacral Dysplasia according to GeneCards/GeneDecks:

(show all 38)
idCompoundScoreTop Affiliating Genes
1hydroxamate4410.0MMP9, ZMPSTE24
21,10-phenanthroline44 211.0ZMPSTE24, MMP9
3indinavir44 50 1112.0LMNA, PPARG
4gw966244 2810.9MMP9, PPARG
5batimastat44 61 1111.9MMP9, ZMPSTE24
6irbesartan44 28 50 1112.9MMP9, PPARG
7ciglitazone44 2810.8PPARG, MMP9
8actos449.8INS, PPARG
9hbig449.7INS, PPARG
10mitiglinide44 1110.7PPARG, INS
11glipizide44 50 1111.7INS, PPARG
12acarbose44 1110.7INS, PPARG
13repaglinide50 44 1111.7PPARG, INS
14nateglinide44 50 1111.7INS, PPARG
15glimepiride44 50 1111.7INS, PPARG
16telmisartan44 28 1111.7PPARG, INS
17orlistat44 61 1111.7INS, PPARG
188-isoprostane449.7MMP9, INS
19thiazolidinedione449.7PPARG, INS
20gemfibrozil28 44 1111.6PPARG, INS
21niacin44 1110.6PPARG, INS
22aicar44 24 1111.6PPARG, INS
23l-nmma449.6PPARG, MMP9
24bezafibrate44 28 1111.6PPARG, INS
25alpha lipoic acid449.5MMP9, INS
26ritonavir44 50 1111.4INS, PPARG
27tripeptide449.3RCE1, ZMPSTE24
28fenofibrate44 50 1111.3PPARG, INS, MMP9
29pioglitazone28 44 50 1112.3MMP9, INS, PPARG
30troglitazone44 28 61 1112.3PPARG, INS, MMP9
312-deoxyglucose44 1110.2INS, PPARG
32zinc44 2410.2LMNA, MMP9, CBX1, ZMPSTE24
33cholesterol44 28 24 1112.1PPARG, INS, LMNA, ZMPSTE24
34ly294002449.1MMP9, INS, PPARG
35metformin44 50 1111.0PPARG, INS
36rosiglitazone28 44 50 24 1113.0MMP9, LMNA, INS, PPARG
37alanine448.9MMP9, LMNA, INS, PPARG
38lipid448.7AGPAT2, LMNA, INS, PPARG

GO Terms for genes affiliated with Mandibuloacral Dysplasia

About this section

Cellular components related to Mandibuloacral Dysplasia according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1nucleoplasmGO:0056548.8BANF1, CBX1, LMNA, PPARG

Biological processes related to Mandibuloacral Dysplasia according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1mitotic nuclear envelope reassemblyGO:0070849.8BANF1, LMNA
2mitotic nuclear envelope disassemblyGO:0070779.8BANF1, LMNA
3negative regulation of acute inflammatory responseGO:0026749.4INS, PPARG
4negative regulation of lipid catabolic processGO:0509959.3BSCL2, INS
5proteolysisGO:0065088.6RCE1, ZMPSTE24, MMP9

Molecular functions related to Mandibuloacral Dysplasia according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1metalloendopeptidase activityGO:0042228.9RCE1, ZMPSTE24, MMP9

Products for genes affiliated with Mandibuloacral Dysplasia

About this section
  • Antibodies
  • Proteins
  • Lysates

Sources for Mandibuloacral Dysplasia

About this section
3CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
28IUPHAR
29KEGG
34MeSH
35MESH via Orphanet
36MGI
39NCIt
40NDF-RT
43NINDS
44Novoseek
46OMIM
47OMIM via Orphanet
51PubMed
52QIAGEN
58SNOMED-CT via Orphanet
62UMLS
63UMLS via Orphanet