MCID: SPL024
MIFTS: 45

Split-Hand/foot Malformation 3

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

Aliases & Classifications for Split-Hand/foot Malformation 3

MalaCards integrated aliases for Split-Hand/foot Malformation 3:

Name: Split-Hand/foot Malformation 3 57 75 73
Shfm3 57 12 75 55
Chromosome 10q24 Duplication Syndrome 57 12 75
Split-Hand/foot Malformation 3, Gene Duplication Syndrome 57 13
Limb Deficiencies, Distal, with Micrognathia 57 75
Limb Deficiencies Distal with Micrognathia 53 29
Split Hand-Foot Malformation 3 12 15
Shsf3 57 75
Split-Hand/foot Malformation, Type 3, Gene Duplication Syndrome 40
Distal Limb Deficiencies-Micrognathia Syndrome 59
Distal Limb Deficiencies with Micrognathia 12
10q24 Microduplication Syndrome 59
Buttiens Fryns Syndrome 53
Buttiens-Fryns Syndrome 59

Characteristics:

Orphanet epidemiological data:

59
distal limb deficiencies-micrognathia syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Neonatal;

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
preaxial involvement in approximately 60% of patients
contiguous gene duplication syndrome
linked to 10q24 trisomy


HPO:

32
split-hand/foot malformation 3:
Inheritance autosomal recessive inheritance autosomal dominant inheritance


Classifications:



Summaries for Split-Hand/foot Malformation 3

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 1307Disease definitionThe distal limb deficiencies-micrognathiasyndrome is characterized by the combination of symmetric severe distal limb reduction deficiencies affecting all four limbs (oligodactyly), microretrognathia, and microstomia with or without cleft palate.EpidemiologyIt has been reported in four patients; two of them were siblings and had moderate intellectual deficiency.Clinical descriptionTwo non-related subjects also had severe myopia, bilateral conductive hearing loss and a renal change, referred to as oligomeganephronia, or renal hypoplasia.EtiologyUsing high resolution oligoarray-based comparative genomic hybridization (aCGH), a 10q24 duplication or triplication was recently detected in all these patients, similar to the duplication detected in an isolated form of split hand foot malformation (SHFM; see this term).Visit the Orphanet disease page for more resources.

MalaCards based summary : Split-Hand/foot Malformation 3, also known as shfm3, is related to split-hand/foot malformation 1 and split hand-foot malformation. An important gene associated with Split-Hand/foot Malformation 3 is SHFM3 (Split-Hand/Foot Malformation 3), and among its related pathways/superpathways are Signaling by Hedgehog and Hedgehog Pathway. Affiliated tissues include bone, and related phenotypes are macrocephaly and high palate

OMIM : 57 Split-hand/split-foot malformation is a limb malformation involving the central rays of the autopod and presenting with syndactyly, median clefts of the hands and feet, and aplasia and/or hypoplasia of the phalanges, metacarpals, and metatarsals. Some patients with SHFM3 have been found to have mental retardation, ectodermal and craniofacial findings, and orofacial clefting (Elliott and Evans, 2006). For additional phenotypic information and a discussion of genetic heterogeneity in this disorder, see SHFM1 (183600). (246560)

UniProtKB/Swiss-Prot : 75 Split-hand/foot malformation 3: A limb malformation involving the central rays of the autopod and presenting with syndactyly, median clefts of the hands and feet, and aplasia and/or hypoplasia of the phalanges, metacarpals, and metatarsals. Some patients have been found to have mental retardation, ectodermal and craniofacial findings, and orofacial clefting.

Disease Ontology : 12 A split-hand/foot malformation that has material basis in a contiguous gene duplication syndrome on chromosome 10q24

Related Diseases for Split-Hand/foot Malformation 3

Graphical network of the top 20 diseases related to Split-Hand/foot Malformation 3:



Diseases related to Split-Hand/foot Malformation 3

Symptoms & Phenotypes for Split-Hand/foot Malformation 3

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Mouth:
cleft palate
high-arched palate

Skeletal Hands:
split hand
ectrodactyly
camptodactyly

Head And Neck Ears:
dysplastic ears
hearing loss, conductive or mixed

Skin Nails Hair Nails:
dystrophic nails
ridged nails

Genitourinary Kidneys:
renal hypoplasia

Skeletal Feet:
ectrodactyly
split feet

Neurologic Central Nervous System:
mental retardation (in some patients)

Head And Neck Face:
micrognathia (in some patients)
maxillary hypoplasia (in some patients)


Clinical features from OMIM:

246560

Human phenotypes related to Split-Hand/foot Malformation 3:

59 32 (show all 36)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 macrocephaly 59 32 occasional (7.5%) Occasional (29-5%) HP:0000256
2 high palate 59 32 frequent (33%) Frequent (79-30%) HP:0000218
3 nystagmus 59 32 occasional (7.5%) Occasional (29-5%) HP:0000639
4 abnormality of the ulna 59 32 occasional (7.5%) Occasional (29-5%) HP:0002997
5 sensorineural hearing impairment 59 32 occasional (7.5%) Occasional (29-5%) HP:0000407
6 short stature 59 32 occasional (7.5%) Occasional (29-5%) HP:0004322
7 renal insufficiency 59 32 frequent (33%) Frequent (79-30%) HP:0000083
8 proteinuria 59 32 frequent (33%) Frequent (79-30%) HP:0000093
9 cleft palate 59 32 occasional (7.5%) Occasional (29-5%) HP:0000175
10 microdontia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000691
11 cryptorchidism 59 32 frequent (33%) Frequent (79-30%) HP:0000028
12 myopia 59 32 frequent (33%) Frequent (79-30%) HP:0000545
13 prominent nasal bridge 59 32 occasional (7.5%) Occasional (29-5%) HP:0000426
14 intellectual disability, moderate 59 32 frequent (33%) Frequent (79-30%) HP:0002342
15 abnormality of the metacarpal bones 59 32 hallmark (90%) Very frequent (99-80%) HP:0001163
16 hypoplasia of the maxilla 59 32 occasional (7.5%) Very frequent (99-80%) HP:0000327
17 low-set, posteriorly rotated ears 59 32 hallmark (90%) Very frequent (99-80%) HP:0000368
18 narrow mouth 59 32 frequent (33%) Frequent (79-30%) HP:0000160
19 conductive hearing impairment 59 32 frequent (33%) Frequent (79-30%) HP:0000405
20 renal hypoplasia 59 32 frequent (33%) Frequent (79-30%) HP:0000089
21 abnormality of the ankles 59 32 hallmark (90%) Very frequent (99-80%) HP:0003028
22 microretrognathia 59 32 hallmark (90%) Very frequent (99-80%) HP:0000308
23 tarsal synostosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0008368
24 aplasia/hypoplasia of the thumb 59 32 frequent (33%) Frequent (79-30%) HP:0009601
25 oligodactyly 59 32 hallmark (90%) Very frequent (99-80%) HP:0012165
26 aplasia/hypoplasia of the radius 59 32 frequent (33%) Frequent (79-30%) HP:0006501
27 abnormality of the wrist 59 32 frequent (33%) Frequent (79-30%) HP:0003019
28 abnormality of chromosome segregation 59 32 hallmark (90%) Very frequent (99-80%) HP:0002916
29 split foot 59 32 occasional (7.5%) Occasional (29-5%) HP:0001839
30 microglossia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000171
31 intellectual disability 32 HP:0001249
32 nail dystrophy 32 HP:0008404
33 abnormality of the pinna 32 HP:0000377
34 split hand 32 HP:0001171
35 ridged nail 32 HP:0001807
36 camptodactyly 32 HP:0012385

MGI Mouse Phenotypes related to Split-Hand/foot Malformation 3:

46 (show all 14)
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 10.26 BTRC DLX5 DPCD FGF8 GLI1 LBX1
2 cardiovascular system MP:0005385 10.24 SNCA SUFU TP63 BTRC DLX1 DLX2
3 growth/size/body region MP:0005378 10.2 DLX5 DPCD FGF8 GLI1 LBX1 SNCA
4 mortality/aging MP:0010768 10.18 TP63 BTRC DLX1 DLX2 DLX5 DPCD
5 digestive/alimentary MP:0005381 10.15 BTRC DLX1 DLX2 DLX5 FGF8 GLI1
6 embryo MP:0005380 10.13 DLX5 FBXW4 FGF8 GLI1 LBX1 PAX2
7 craniofacial MP:0005382 10.11 DLX2 DLX5 DPCD FGF8 GLI1 SUFU
8 nervous system MP:0003631 10.06 TLX1 DLX1 DLX2 DLX5 DPCD FGF8
9 limbs/digits/tail MP:0005371 9.95 DLX5 FBXW4 FGF8 GLI1 LBX1 SUFU
10 hearing/vestibular/ear MP:0005377 9.91 DLX1 DLX2 DLX5 DPCD FGF8 PAX2
11 no phenotypic analysis MP:0003012 9.8 DLX1 FBXW4 GLI1 SNCA SUFU TP63
12 reproductive system MP:0005389 9.76 BTRC DPCD FGF8 GLI1 PAX2 POLL
13 respiratory system MP:0005388 9.5 DLX2 DLX5 DPCD FGF8 GLI1 SUFU
14 skeleton MP:0005390 9.32 BTRC DLX1 DLX2 DLX5 DPCD FBXW4

Drugs & Therapeutics for Split-Hand/foot Malformation 3

Search Clinical Trials , NIH Clinical Center for Split-Hand/foot Malformation 3

Genetic Tests for Split-Hand/foot Malformation 3

Genetic tests related to Split-Hand/foot Malformation 3:

# Genetic test Affiliating Genes
1 Limb Deficiencies Distal with Micrognathia 29

Anatomical Context for Split-Hand/foot Malformation 3

MalaCards organs/tissues related to Split-Hand/foot Malformation 3:

41
Bone

Publications for Split-Hand/foot Malformation 3

Articles related to Split-Hand/foot Malformation 3:

# Title Authors Year
1
Distal limb deficiencies, micrognathia syndrome, and syndromic forms of split hand foot malformation (SHFM) are caused by chromosome 10q genomic rearrangements. ( 19584065 )
2010

Variations for Split-Hand/foot Malformation 3

Expression for Split-Hand/foot Malformation 3

Search GEO for disease gene expression data for Split-Hand/foot Malformation 3.

Pathways for Split-Hand/foot Malformation 3

Pathways related to Split-Hand/foot Malformation 3 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.8 BTRC GLI1 SEM1 SUFU
2
Show member pathways
11.44 BTRC GLI1 SUFU
3
Show member pathways
11.1 BTRC GLI1 SUFU WNT10B

GO Terms for Split-Hand/foot Malformation 3

Cellular components related to Split-Hand/foot Malformation 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nucleus GO:0005634 9.44 BTRC DLX1 DLX2 DLX5 DPCD GLI1

Biological processes related to Split-Hand/foot Malformation 3 according to GeneCards Suite gene sharing:

(show all 33)
# Name GO ID Score Top Affiliating Genes
1 positive regulation of transcription by RNA polymerase II GO:0045944 9.86 DLX1 DLX2 DLX5 GLI1 PAX2 TLX1
2 skeletal system development GO:0001501 9.83 DLX5 SUFU TP63
3 positive regulation of canonical Wnt signaling pathway GO:0090263 9.82 DLX5 SEM1 WNT10B
4 negative regulation of neuron apoptotic process GO:0043524 9.81 DLX1 FGF8 SNCA
5 canonical Wnt signaling pathway GO:0060070 9.78 FGF8 GLI1 WNT10B
6 determination of left/right symmetry GO:0007368 9.76 DPCD FGF8 SUFU
7 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process GO:0031146 9.75 BTRC FBXW4 SEM1
8 inner ear morphogenesis GO:0042472 9.74 DLX5 FGF8 PAX2
9 heart looping GO:0001947 9.71 FGF8 LBX1 SUFU
10 odontogenesis of dentin-containing tooth GO:0042475 9.7 DLX1 DLX2 TP63
11 embryonic limb morphogenesis GO:0030326 9.69 DLX5 FBXW4 TP63
12 positive regulation of mesenchymal cell proliferation GO:0002053 9.66 FBXW4 TP63
13 negative regulation of smoothened signaling pathway GO:0045879 9.65 BTRC SUFU
14 positive regulation of cell differentiation GO:0045597 9.65 DLX1 DLX2 FGF8
15 anatomical structure formation involved in morphogenesis GO:0048646 9.64 DLX5 TP63
16 prostate gland development GO:0030850 9.63 GLI1 TP63
17 mesonephros development GO:0001823 9.62 FGF8 PAX2
18 negative regulation of oligodendrocyte differentiation GO:0048715 9.61 DLX1 DLX2
19 forebrain neuron differentiation GO:0021879 9.59 DLX1 DLX2
20 epidermal cell differentiation GO:0009913 9.55 GLI1 TP63
21 negative regulation of photoreceptor cell differentiation GO:0046533 9.49 DLX1 DLX2
22 cerebral cortex GABAergic interneuron differentiation GO:0021892 9.43 DLX1 DLX2
23 regulation of transcription from RNA polymerase II promoter involved in forebrain neuron fate commitment GO:0021882 9.4 DLX1 DLX2
24 multicellular organism development GO:0007275 9.4 DLX1 DLX2 DLX5 FBXW4 FGF8 GLI1
25 positive regulation of amacrine cell differentiation GO:1902871 9.37 DLX1 DLX2
26 subpallium development GO:0021544 9.33 DLX1 DLX2 FGF8
27 cerebral cortex GABAergic interneuron fate commitment GO:0021893 9.32 DLX1 DLX2
28 proximal/distal pattern formation GO:0009954 9.26 DLX1 DLX2 GLI1 TP63
29 regulation of transcription, DNA-templated GO:0006355 10.25 DLX1 DLX2 DLX5 GLI1 LBX1 PAX2
30 transcription by RNA polymerase II GO:0006366 10.03 DLX2 DLX5 PAX2 TLX1 TP63
31 negative regulation of transcription by RNA polymerase II GO:0000122 10.03 DLX1 DLX2 SNCA SUFU TP63 WNT10B
32 positive regulation of transcription, DNA-templated GO:0045893 10.02 BTRC DLX5 GLI1 PAX2 TP63
33 cell differentiation GO:0030154 10 DLX1 DLX2 FGF8 GLI1 LBX1 PAX2

Molecular functions related to Split-Hand/foot Malformation 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 DNA binding GO:0003677 9.91 DLX1 DLX2 DLX5 GLI1 LBX1 PAX2
2 sequence-specific DNA binding GO:0043565 9.63 DLX1 DLX2 DLX5 LBX1 TLX1 TP63
3 RNA polymerase II transcription factor activity, sequence-specific DNA binding GO:0000981 9.56 DLX1 DLX2 DLX5 GLI1 LBX1 PAX2
4 transcription regulatory region DNA binding GO:0044212 9.02 DLX5 GLI1 PAX2 SNCA TP63

Sources for Split-Hand/foot Malformation 3

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
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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