MADAC
MCID: MCR364
MIFTS: 41

Macrodactyly (MADAC)

Categories: Fetal diseases, Genetic diseases, Rare diseases

Aliases & Classifications for Macrodactyly

MalaCards integrated aliases for Macrodactyly:

Name: Macrodactyly 57 72
Congenital Macrodactylia 72 29 6
Macrodactyly, Somatic 57 6
Megalodactyly 57 72
Type I Macrodactyly 72
Madac 72

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
somatic mutation


HPO:

31
macrodactyly:
Inheritance somatic mutation


Classifications:



External Ids:

OMIM® 57 155500
MeSH 44 D017880
MedGen 41 C0265552
SNOMED-CT via HPO 68 124975008 48449000

Summaries for Macrodactyly

OMIM® : 57 Macrodactyly is a congenital anomaly characterized by fibrofatty tissue enlargement and bony overgrowth in affected digits with resultant loss of function. Macrodactyly affects a 'nerve territory,' and the individual peripheral nerve is both enlarged and elongated (summary by Rios et al., 2013). (155500) (Updated 20-May-2021)

MalaCards based summary : Macrodactyly, also known as congenital macrodactylia, is related to congenital lipomatous overgrowth, vascular malformations, and epidermal nevi and proteus syndrome. An important gene associated with Macrodactyly is PIK3CA (Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha), and among its related pathways/superpathways are Nanog in Mammalian ESC Pluripotency and Prion disease. Affiliated tissues include breast, bone marrow and heart, and related phenotypes are macrodactyly and Decreased shRNA abundance (Z-score < -2)

UniProtKB/Swiss-Prot : 72 Macrodactyly: A congenital anomaly characterized by fibrofatty tissue enlargement and bony overgrowth affecting the digits or the entire hand or foot.

Wikipedia : 73 Local gigantism or localised gigantism is a condition in which a certain part of the body acquires... more...

Related Diseases for Macrodactyly

Diseases in the Macrodactyly family:

Macrodactyly of Toes

Diseases related to Macrodactyly via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 80)
# Related Disease Score Top Affiliating Genes
1 congenital lipomatous overgrowth, vascular malformations, and epidermal nevi 31.2 TSC1 PIK3CA
2 proteus syndrome 30.1 TSC1 PIK3CA
3 macrodactyly of fingers 11.6
4 epiphyseal chondrodysplasia, miura type 11.4
5 macrodactyly of toes 11.3
6 macrodactyly of fingers, bilateral 11.1
7 macrodactyly of fingers, unilateral 11.1
8 macrodactyly of toes, bilateral 11.1
9 macrodactyly of toes, unilateral 11.1
10 overgrowth syndrome 10.5
11 congenital heart defects, hamartomas of tongue, and polysyndactyly 10.5
12 neurofibromatosis 10.3
13 chromosome 2q35 duplication syndrome 10.3
14 carpal tunnel syndrome 10.3
15 gigantism 10.3
16 tuberous sclerosis 10.3
17 tuberous sclerosis 1 10.1
18 klippel-trenaunay-weber syndrome 10.1
19 hemihyperplasia, isolated 10.1
20 nevus, epidermal 10.0
21 polydactyly 10.0
22 lipomatosis 10.0
23 weber syndrome 10.0
24 angioosteohypertrophic syndrome 10.0
25 keloid formation 9.9
26 lipomatosis, multiple 9.9
27 pleomorphic lipoma 9.9
28 lymphangioma 9.9
29 hyperostosis 9.9
30 neurilemmoma 9.9
31 plexiform schwannoma 9.9
32 keloid disorder 9.9
33 congenital lymphedema 9.9
34 rare lymphatic malformation 9.9
35 breast cancer 9.8
36 colorectal cancer 9.8
37 hepatocellular carcinoma 9.8
38 lymphatic malformation 1 9.8
39 neurofibromatosis, type i 9.8
40 keratosis, seborrheic 9.8
41 renal hypodysplasia/aplasia 1 9.8
42 lung cancer 9.8
43 macrocephaly/megalencephaly syndrome, autosomal recessive 9.8
44 capillary malformation of the lower lip, lymphatic malformation of face and neck, asymmetry of face and limbs, and partial/generalized overgrowth 9.8
45 gastric cancer 9.8
46 multiple enchondromatosis, maffucci type 9.8
47 hereditary lymphedema 9.8
48 brachydactyly 9.8
49 scoliosis 9.8
50 hereditary lymphedema ia 9.8

Graphical network of the top 20 diseases related to Macrodactyly:



Diseases related to Macrodactyly

Symptoms & Phenotypes for Macrodactyly

Human phenotypes related to Macrodactyly:

31
# Description HPO Frequency HPO Source Accession
1 macrodactyly 31 HP:0004099

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Skeletal Hands:
one or 2 extraordinarily enlarged fingers

Clinical features from OMIM®:

155500 (Updated 20-May-2021)

GenomeRNAi Phenotypes related to Macrodactyly according to GeneCards Suite gene sharing:

26 (show all 36)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-104 10.09 E2F1
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-105 10.09 E2F1
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-107 10.09 E2F1
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-116 10.09 E2F1 PIK3CA
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-117 10.09 TSC1
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-122 10.09 E2F1
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-126 10.09 E2F1
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-130 10.09 E2F1
9 Decreased shRNA abundance (Z-score < -2) GR00366-A-139 10.09 E2F1
10 Decreased shRNA abundance (Z-score < -2) GR00366-A-149 10.09 MAPT
11 Decreased shRNA abundance (Z-score < -2) GR00366-A-157 10.09 PIK3CA
12 Decreased shRNA abundance (Z-score < -2) GR00366-A-16 10.09 PIK3CA
13 Decreased shRNA abundance (Z-score < -2) GR00366-A-166 10.09 PIK3CA
14 Decreased shRNA abundance (Z-score < -2) GR00366-A-177 10.09 PIK3CA
15 Decreased shRNA abundance (Z-score < -2) GR00366-A-190 10.09 PIK3CA
16 Decreased shRNA abundance (Z-score < -2) GR00366-A-195 10.09 E2F1
17 Decreased shRNA abundance (Z-score < -2) GR00366-A-203 10.09 TSC1
18 Decreased shRNA abundance (Z-score < -2) GR00366-A-206 10.09 TSC1
19 Decreased shRNA abundance (Z-score < -2) GR00366-A-207 10.09 E2F1
20 Decreased shRNA abundance (Z-score < -2) GR00366-A-216 10.09 PIK3CA
21 Decreased shRNA abundance (Z-score < -2) GR00366-A-33 10.09 TSC1
22 Decreased shRNA abundance (Z-score < -2) GR00366-A-42 10.09 PIK3CA
23 Decreased shRNA abundance (Z-score < -2) GR00366-A-49 10.09 PIK3CA
24 Decreased shRNA abundance (Z-score < -2) GR00366-A-53 10.09 PIK3CA
25 Decreased shRNA abundance (Z-score < -2) GR00366-A-82 10.09 TSC1
26 Decreased shRNA abundance (Z-score < -2) GR00366-A-87 10.09 MAPT
27 Decreased viability GR00055-A-1 9.36 PIK3CA
28 Decreased viability GR00055-A-2 9.36 PIK3CA
29 Decreased viability GR00221-A-1 9.36 E2F1 PIK3CA
30 Decreased viability GR00221-A-2 9.36 E2F1 PIK3CA TSC1
31 Decreased viability GR00221-A-3 9.36 TSC1
32 Decreased viability GR00221-A-4 9.36 PIK3CA
33 Decreased viability GR00301-A 9.36 TSC1
34 Decreased viability GR00402-S-2 9.36 PIK3CA
35 Decreased cell migration GR00055-A-1 9.33 NPR2 TSC1
36 Decreased cell migration GR00055-A-3 9.33 PIK3CA

MGI Mouse Phenotypes related to Macrodactyly:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.91 E2F1 GRIN3A MAPT NPR2 PIK3CA PTN
2 muscle MP:0005369 9.72 E2F1 MAPT NPR2 PIK3CA TSC1
3 nervous system MP:0003631 9.7 E2F1 GRIN3A MAPT NPR2 PIK3CA PTN
4 neoplasm MP:0002006 9.56 E2F1 MAPT PIK3CA TSC1
5 reproductive system MP:0005389 9.43 E2F1 GRIN3A NPR2 PIK3CA PTN TSC1
6 vision/eye MP:0005391 9.02 E2F1 GRIN3A MAPT PIK3CA TSC1

Drugs & Therapeutics for Macrodactyly

Search Clinical Trials , NIH Clinical Center for Macrodactyly

Genetic Tests for Macrodactyly

Genetic tests related to Macrodactyly:

# Genetic test Affiliating Genes
1 Congenital Macrodactylia 29 PIK3CA

Anatomical Context for Macrodactyly

MalaCards organs/tissues related to Macrodactyly:

40
Breast, Bone Marrow, Heart, Lung, Tongue, Bone, Skin

Publications for Macrodactyly

Articles related to Macrodactyly:

(show top 50) (show all 380)
# Title Authors PMID Year
1
Somatic gain-of-function mutations in PIK3CA in patients with macrodactyly. 6 57 61
23100325 2013
2
Isolated macrodactyly and Proteus syndrome. 61 57
8818455 1996
3
Macrodactyly. 57 61
4293291 1967
4
CLAPO syndrome: identification of somatic activating PIK3CA mutations and delineation of the natural history and phenotype. 6
29446767 2018
5
Reactivation of multipotency by oncogenic PIK3CA induces breast tumour heterogeneity. 6
26266985 2015
6
PIK3CA(H1047R) induces multipotency and multi-lineage mammary tumours. 6
26266975 2015
7
Mosaic overgrowth with fibroadipose hyperplasia is caused by somatic activating mutations in PIK3CA. 6
22729222 2012
8
Somatic mosaic activating mutations in PIK3CA cause CLOVES syndrome. 6
22658544 2012
9
Oncogenic PIK3CA mutations occur in epidermal nevi and seborrheic keratoses with a characteristic mutation pattern. 6
17673550 2007
10
PIK3CA gene is frequently mutated in breast carcinomas and hepatocellular carcinomas. 6
15608678 2005
11
Mutation of the PIK3CA gene in ovarian and breast cancer. 6
15520168 2004
12
High frequency of mutations of the PIK3CA gene in human cancers. 6
15016963 2004
13
Megalodactylism. Report of 7 cases. 57
6035453 1967
14
Phalangectomy combination double-pedicled digital artery flap for second-toe macrodactyly reconstruction: A case report. 61
33752034 2021
15
Clinical characteristics of 93 cases of isolated macrodactyly of the foot in children. 61
33557883 2021
16
Lipofibromatous hamartoma of the median nerve and its terminal branches: recurrent branch and ulnar proper palmar digital nerve of the thumb. A case report. 61
32889169 2021
17
Isolated Acquired Macrodactyly of the Left Fourth Toe. 61
33585134 2021
18
Macrodactyly in tuberous sclerosis complex. 61
33511660 2021
19
Surgical management for isolated macrodactyly in an adult PIK3CA mutant. 61
33251316 2020
20
Macrodactyly of the foot resulting from plantar nerve impairment. 61
33384233 2020
21
Superimposed mosaicism in tuberous sclerosis complex: a key to understanding all of the manifold manifestations? 61
32396651 2020
22
Shortening Scarf Osteotomy for Macrodactyly and Valgus of the Hallux in Acrodysostosis Lesser Toes Brachydactyly. 61
33215519 2020
23
Truncal Varicosities and Bilateral Port-wine Stain with Spinal Deformities Associated with Klippel-Trenaunay-Weber Syndrome. 61
33487708 2020
24
Lipofibromatous Hamartoma in a Hispanic Patient with macrodactyly: a rare peripheral nerve tumor causing recurrent carpal tunnel syndrome. 61
33154809 2020
25
Clinical Characteristics of 90 Macrodactyly Cases. 61
32299688 2020
26
Phenotypic and genetic spectrum of isolated macrodactyly: somatic mosaicism of PIK3CA and AKT1 oncogenic variants. 61
33054853 2020
27
A Child with Enlarged Extremities - A Case of Macrodystrophia Lipomatosa. 61
33165351 2020
28
Proteus syndrome of the foot: A case report and literature review. 61
32765766 2020
29
What's New in Congenital Hand Surgery. 61
32658157 2020
30
Ultrasonographic Diagnosis of Lipomatosis of Nerve: A Review of Ultrasonographic Finding for 8 Cases. 61
32344138 2020
31
Activating PIK3CA mutation promotes osteogenesis of bone marrow mesenchymal stem cells in macrodactyly. 61
32632138 2020
32
Activating PIK3CA mutation promotes adipogenesis of adipose-derived stem cells in macrodactyly via up-regulation of E2F1. 61
32732866 2020
33
An Activating Deletion Variant in the Submembrane Region of Natriuretic Peptide Receptor-B Causes Tall Stature. 61
32282051 2020
34
Rheumatoid Arthritis and CLOVES Syndrome: A Tricky Diagnosis. 61
32660056 2020
35
Ulnar Nerve Entrapment at Elbow in an Adult Patient with Macrodactyly. 61
32312213 2020
36
PIK3CA mutations in lipomatosis of nerve with or without nerve territory overgrowth. 61
31481664 2020
37
Clinical report: one year of treatment of Proteus syndrome with miransertib (ARQ 092). 61
32014856 2020
38
Forefoot malformations, deformities and other congenital defects in children. 61
31648997 2020
39
Precise Resection of Macrodactyly Under Assistance of Three-Dimensional Reconstruction Technology: A Case Report. 61
31882135 2020
40
Proteus Syndrome, a rare case with an unusual presentation: Case report. 61
32563816 2020
41
Macrodystrophia lipomatosa with fibrolipomatous hamartoma of medial plantar nerve and lipomatosis of thigh. 61
32528203 2020
42
Lipofibromatous hamartoma of the median nerve with macrodactyly of middle finger. 61
31708632 2019
43
A Novel Method of Treatment of Macrodactyly with Digital Nerve Resection and Nerve Allograft. 61
31772904 2019
44
[Macrodactyly of the thumb in connection to a lipofibromatous hamartoma of the median nerve in the carpal tunnel]. 61
31167283 2019
45
Recurrence of carpal tunnel syndrome in isolated non-syndromic macrodactyly: DTI examination of a giant median nerve. 61
30343441 2019
46
Parenting stress in mothers of children with congenital hand or foot differences and its effect on the surgical decision-making for their children. 61
30939996 2019
47
Hyperhidrotic Macrodactylism Caused by Osteoid Osteoma: A Case Report and Review of the Literature. 61
30745269 2019
48
Lipomatosis of the brachial plexus with associated overgrowth and macrodactyly. 61
30230612 2019
49
Keloid formation after syndactyly release in a patient with macrodactyly - methotrexate treatment. 61
29973103 2019
50
Insights into the pathogenesis of macrodactyly. 61
30086673 2019

Variations for Macrodactyly

ClinVar genetic disease variations for Macrodactyly:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 PIK3CA NM_006218.4(PIK3CA):c.3140A>G (p.His1047Arg) SNV Pathogenic 13652 rs121913279 GRCh37: 3:178952085-178952085
GRCh38: 3:179234297-179234297
2 PIK3CA NM_006218.4(PIK3CA):c.3139C>T (p.His1047Tyr) SNV Pathogenic 39705 rs121913281 GRCh37: 3:178952084-178952084
GRCh38: 3:179234296-179234296
3 PIK3CA PIK3CA, ARG115PRO SNV Pathogenic 585022 GRCh37:
GRCh38:
4 PIK3CA NM_006218.4(PIK3CA):c.436G>A (p.Val146Ile) SNV Uncertain significance 526641 rs755969956 GRCh37: 3:178917561-178917561
GRCh38: 3:179199773-179199773
5 PIK3CA NM_006218.4(PIK3CA):c.1130C>G (p.Pro377Arg) SNV Uncertain significance 403909 rs113613074 GRCh37: 3:178922361-178922361
GRCh38: 3:179204573-179204573

Expression for Macrodactyly

Search GEO for disease gene expression data for Macrodactyly.

Pathways for Macrodactyly

Pathways related to Macrodactyly according to GeneCards Suite gene sharing:

(show all 13)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.72 TSC1 PTN NPR2 MAPT
2
Show member pathways
12.42 PIK3CA MAPT GRIN3A
3
Show member pathways
12.18 TSC1 PIK3CA E2F1
4
Show member pathways
11.79 TSC1 PIK3CA MAPT
5
Show member pathways
11.62 TSC1 PIK3CA E2F1
6 11.47 PIK3CA E2F1
7 11.46 TSC1 PIK3CA
8 11.31 PIK3CA E2F1
9
Show member pathways
11.28 PIK3CA E2F1
10
Show member pathways
11.25 PIK3CA E2F1
11 11.05 PIK3CA MAPT
12 10.99 TSC1 PIK3CA E2F1
13 10.42 PIK3CA MAPT

GO Terms for Macrodactyly

Biological processes related to Macrodactyly according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 liver development GO:0001889 9.4 PTN PIK3CA
2 memory GO:0007613 9.37 PTN MAPT
3 synapse organization GO:0050808 9.32 TSC1 MAPT
4 regulation of synaptic plasticity GO:0048167 9.26 PTN MAPT
5 cellular response to nerve growth factor stimulus GO:1990090 9.16 MAPT E2F1
6 negative regulation of macroautophagy GO:0016242 8.96 TSC1 PIK3CA
7 anoikis GO:0043276 8.62 PIK3CA E2F1

Molecular functions related to Macrodactyly according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein kinase binding GO:0019901 9.33 PTN MAPT E2F1
2 Hsp90 protein binding GO:0051879 8.96 TSC1 MAPT
3 protein phosphatase 2A binding GO:0051721 8.62 MAPT GRIN3A

Sources for Macrodactyly

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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