MCID: HRT030
MIFTS: 43

Hartsfield Syndrome

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

Aliases & Classifications for Hartsfield Syndrome

MalaCards integrated aliases for Hartsfield Syndrome:

Name: Hartsfield Syndrome 54 23 24 25 56 71 29
Holoprosencephaly, Ectrodactyly and Bilateral Cleft Lip/palate 24 71
Hrtfds 24 71
Holoprosencephaly, Ectrodactyly, and Bilateral Cleft Lip/palate 25
Holoprosencephaly, Ectrodactyly, and Bilateral Cleft Lip-Palate 69
Holoprosencephaly, Hypertelorism, and Ectrodactyly Syndrome 25
Holoprosencephaly-Ectrodactyly-Cleft Lip/palate Syndrome 56
Holoprosencephaly and Split Hand/foot Syndrome 25
Hartsfield-Bixler-Demyer Syndrome 25
Hhes 25

Characteristics:

Orphanet epidemiological data:

56
hartsfield syndrome
Inheritance: Autosomal dominant,Autosomal recessive; Prevalence: <1/1000000 (Worldwide);

OMIM:

54
Inheritance:
autosomal dominant


HPO:

32
hartsfield syndrome:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Hartsfield Syndrome

OMIM : 54
Hartsfield syndrome classically refers to the triad of holoprosencephaly, ectrodactyly, and cleft/lip palate. Profound mental retardation is also present. Multiple other congenital anomalies usually occur (Vilain et al., 2009). The disorder involves midline and limb field defects (Zechi-Ceide et al., 2009). See also ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome (EEC; 129900), which shows phenotypic similarities. (615465)

MalaCards based summary : Hartsfield Syndrome, also known as holoprosencephaly, ectrodactyly and bilateral cleft lip/palate, is related to idiopathic hemiconvulsion-hemiplegia syndrome and holoprosencephaly, and has symptoms including ptosis, depressed nasal bridge and hypertelorism. An important gene associated with Hartsfield Syndrome is FGFR1 (Fibroblast Growth Factor Receptor 1), and among its related pathways/superpathways are Ras signaling pathway and Downstream signaling events of B Cell Receptor (BCR). Affiliated tissues include brain and bone.

Genetics Home Reference : 25 Hartsfield syndrome is a rare condition characterized by holoprosencephaly, which is an abnormality of brain development, and a malformation of the hands and feet called ectrodactyly.

UniProtKB/Swiss-Prot : 71 Hartsfield syndrome: A syndrome characterized by the triad of holoprosencephaly, ectrodactyly, and cleft/lip palate. Profound mental retardation is also present. Multiple other congenital anomalies usually occur.

GeneReviews: NBK349073

Related Diseases for Hartsfield Syndrome

Graphical network of the top 20 diseases related to Hartsfield Syndrome:



Diseases related to Hartsfield Syndrome

Symptoms & Phenotypes for Hartsfield Syndrome

Symptoms via clinical synopsis from OMIM:

54

Head And Neck- Nose:
broad nose

Head And Neck- Ears:
low-set ears
posteriorly rotated ears

Head And Neck- Mouth:
cleft palate
cleft lip

Genitourinary- Internal Genitalia Male:
cryptorchidism

Skeletal- Feet:
syndactyly
ectrodactyly

Endocrine Features:
diabetes insipidus
gonadotropin deficiency

Laboratory- Abnormalities:
hypernatremia

Head And Neck- Head:
microcephaly

Head And Neck- Eyes:
epicanthal folds
hypertelorism
hypotelorism

Genitourinary- External Genitalia Male:
hypospadias
small penis

Neurologic- Central Nervous System:
agenesis of the corpus callosum
hypotonia, neonatal
psychomotor retardation, severe
lobar holoprosencephaly
vermian hypoplasia

Skeletal- Hands:
syndactyly
ectrodactyly

Skeletal- Skull:
hypoplastic frontal bones
craniosynostosis (reported in 1 patient)


Clinical features from OMIM:

615465

Human phenotypes related to Hartsfield Syndrome:

56 32 (show all 36)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 ptosis 56 32 hallmark (90%) Very frequent (99-80%) HP:0000508
2 depressed nasal bridge 56 32 hallmark (90%) Very frequent (99-80%) HP:0005280
3 hypertelorism 56 32 hallmark (90%) Very frequent (99-80%) HP:0000316
4 intrauterine growth retardation 56 32 hallmark (90%) Very frequent (99-80%) HP:0001511
5 cleft palate 56 32 hallmark (90%) Very frequent (99-80%) HP:0000175
6 microphthalmia 56 32 hallmark (90%) Very frequent (99-80%) HP:0000568
7 telecanthus 56 32 hallmark (90%) Very frequent (99-80%) HP:0000506
8 respiratory insufficiency 56 32 hallmark (90%) Very frequent (99-80%) HP:0002093
9 downslanted palpebral fissures 56 32 hallmark (90%) Very frequent (99-80%) HP:0000494
10 low-set, posteriorly rotated ears 56 32 hallmark (90%) Very frequent (99-80%) HP:0000368
11 craniosynostosis 56 32 occasional (7.5%) Very frequent (99-80%) HP:0001363
12 encephalocele 56 32 hallmark (90%) Very frequent (99-80%) HP:0002084
13 split hand 56 32 frequent (33%) Frequent (79-30%) HP:0001171
14 lobar holoprosencephaly 56 32 hallmark (90%) Very frequent (99-80%) HP:0006870
15 non-midline cleft lip 56 32 hallmark (90%) Very frequent (99-80%) HP:0100335
16 aplasia/hypoplasia of the corpus callosum 56 32 hallmark (90%) Very frequent (99-80%) HP:0007370
17 aplasia/hypoplasia of the radius 56 32 frequent (33%) Frequent (79-30%) HP:0006501
18 microcephaly 32 HP:0000252
19 low-set ears 32 HP:0000369
20 micropenis 32 HP:0000054
21 hypospadias 32 HP:0000047
22 posteriorly rotated ears 32 HP:0000358
23 global developmental delay 32 HP:0001263
24 neonatal hypotonia 32 HP:0001319
25 cryptorchidism 32 HP:0000028
26 agenesis of corpus callosum 32 HP:0001274
27 syndactyly 32 HP:0001159
28 hypotelorism 32 HP:0000601
29 epicanthus 32 HP:0000286
30 diabetes insipidus 32 HP:0000873
31 ectrodactyly 32 HP:0100257
32 wide nose 32 HP:0000445
33 gonadotropin deficiency 32 HP:0008213
34 hypernatremia 32 HP:0003228
35 cleft upper lip 32 HP:0000204
36 hypoplasia of the frontal bone 32 HP:0005466

Drugs & Therapeutics for Hartsfield Syndrome

Search Clinical Trials , NIH Clinical Center for Hartsfield Syndrome

Genetic Tests for Hartsfield Syndrome

Genetic tests related to Hartsfield Syndrome:

id Genetic test Affiliating Genes
1 Hartsfield Syndrome 29 24 FGFR1

Anatomical Context for Hartsfield Syndrome

MalaCards organs/tissues related to Hartsfield Syndrome:

39
Brain, Bone

Publications for Hartsfield Syndrome

Articles related to Hartsfield Syndrome:

id Title Authors Year
1
Otorhinolaryngologic manifestations of Hartsfield syndrome: Case series and review of literature. ( 28583501 )
2017
2
Detection of gonadal mosaicism in Hartsfield syndrome by next generation sequencing. ( 27604603 )
2016
3
Dominant-negative kinase domain mutations in FGFR1 can explain the clinical severity of Hartsfield syndrome. ( 26931467 )
2016
4
Hartsfield syndrome associated with a novel heterozygous missense mutation in FGFR1 and incorporating tumoral calcinosis. ( 27170295 )
2016
5
Novel heterozygous mutation in the extracellular domain of FGFR1 associated with Hartsfield syndrome. ( 27790375 )
2016
6
Novel de novo heterozygous FGFR1 mutation in two siblings with Hartsfield syndrome: a case of gonadal mosaicism. ( 24888332 )
2014
7
FGFR1 mutations cause Hartsfield syndrome, the unique association of holoprosencephaly and ectrodactyly. ( 23812909 )
2013
8
Microduplication of Xq24 and Hartsfield syndrome with holoprosencephaly, ectrodactyly, and clefting. ( 22887648 )
2012
9
Hartsfield Syndrome ( 26937548 )
1993

Variations for Hartsfield Syndrome

UniProtKB/Swiss-Prot genetic disease variations for Hartsfield Syndrome:

71
id Symbol AA change Variation ID SNP ID
1 FGFR1 p.Leu165Ser VAR_070851 rs397515481
2 FGFR1 p.Leu191Ser VAR_070852 rs869025669
3 FGFR1 p.Gly490Arg VAR_070853 rs869025670
4 FGFR1 p.Asp623Tyr VAR_070854 rs398122946
5 FGFR1 p.Asn628Lys VAR_070855 rs869025672
6 FGFR1 p.Cys725Tyr VAR_070856 rs398122945
7 FGFR1 p.Arg627Thr VAR_071460 rs869025671

ClinVar genetic disease variations for Hartsfield Syndrome:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 FGFR1 NM_023110.2(FGFR1): c.2174G> A (p.Cys725Tyr) single nucleotide variant Pathogenic rs398122945 GRCh37 Chromosome 8, 38271682: 38271682
2 FGFR1 NM_023110.2(FGFR1): c.494T> C (p.Leu165Ser) single nucleotide variant Pathogenic rs397515481 GRCh37 Chromosome 8, 38285566: 38285566
3 FGFR1 NM_023110.2(FGFR1): c.1867G> T (p.Asp623Tyr) single nucleotide variant Pathogenic rs398122946 GRCh37 Chromosome 8, 38272407: 38272407
4 FGFR1 NM_023110.2(FGFR1): c.1884T> G (p.Asn628Lys) single nucleotide variant Pathogenic rs869025672 GRCh37 Chromosome 8, 38272390: 38272390
5 FGFR1 NM_023110.2(FGFR1): c.1880G> C (p.Arg627Thr) single nucleotide variant Pathogenic rs869025671 GRCh37 Chromosome 8, 38272394: 38272394
6 FGFR1 NM_023110.2(FGFR1): c.1468G> C (p.Gly490Arg) single nucleotide variant Pathogenic/Likely pathogenic rs869025670 GRCh37 Chromosome 8, 38275472: 38275472
7 FGFR1 NM_023110.2(FGFR1): c.572T> C (p.Leu191Ser) single nucleotide variant Pathogenic rs869025669 GRCh37 Chromosome 8, 38285488: 38285488
8 FGFR1 NM_023110.2(FGFR1): c.1454G> T (p.Gly485Val) single nucleotide variant Likely pathogenic rs876661332 GRCh38 Chromosome 8, 38417968: 38417968

Expression for Hartsfield Syndrome

Search GEO for disease gene expression data for Hartsfield Syndrome.

Pathways for Hartsfield Syndrome

Pathways related to Hartsfield Syndrome according to GeneCards Suite gene sharing:

(show all 17)
id Super pathways Score Top Affiliating Genes
1
Show member pathways
12.21 FGF8 FGFR1
2
Show member pathways
12.2 FGF8 FGFR1
3 12.18 FGF8 FGFR1
4
Show member pathways
12.15 FGF8 FGFR1
5 12.12 FGF8 FGFR1
6 12.07 FGF8 FGFR1
7
Show member pathways
12.02 FGF8 FGFR1
8
Show member pathways
11.94 FGF8 FGFR1
9
Show member pathways
11.84 FGF8 FGFR1
10
Show member pathways
11.78 FGF8 FGFR1
11
Show member pathways
11.77 FGF8 FGFR1
12
Show member pathways
11.61 FGF8 FGFR1
13
Show member pathways
11.46 FGF8 FGFR1
14 11.17 FGF8 FGFR1
15 11.16 FGF8 FGFR1
16
Show member pathways
10.91 FGF8 FGFR1
17 10.53 FGF8 FGFR1

GO Terms for Hartsfield Syndrome

Biological processes related to Hartsfield Syndrome according to GeneCards Suite gene sharing:

(show all 13)
id Name GO ID Score Top Affiliating Genes
1 positive regulation of cell proliferation GO:0008284 9.52 FGF8 FGFR1
2 MAPK cascade GO:0000165 9.51 FGF8 FGFR1
3 peptidyl-tyrosine phosphorylation GO:0018108 9.49 FGF8 FGFR1
4 phosphatidylinositol-mediated signaling GO:0048015 9.48 FGF8 FGFR1
5 phosphatidylinositol phosphorylation GO:0046854 9.46 FGF8 FGFR1
6 lung development GO:0030324 9.43 FGF8 FGFR1
7 fibroblast growth factor receptor signaling pathway GO:0008543 9.4 FGF8 FGFR1
8 regulation of phosphatidylinositol 3-kinase signaling GO:0014066 9.37 FGF8 FGFR1
9 inner ear morphogenesis GO:0042472 9.32 FGF8 FGFR1
10 phosphatidylinositol-3-phosphate biosynthetic process GO:0036092 9.26 FGF8 FGFR1
11 generation of neurons GO:0048699 9.16 FGF8 FGFR1
12 branching involved in salivary gland morphogenesis GO:0060445 8.96 FGF8 FGFR1
13 organ induction GO:0001759 8.62 FGF8 FGFR1

Molecular functions related to Hartsfield Syndrome according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 protein tyrosine kinase activity GO:0004713 9.26 FGF8 FGFR1
2 Ras guanyl-nucleotide exchange factor activity GO:0005088 9.16 FGF8 FGFR1
3 phosphatidylinositol-4,5-bisphosphate 3-kinase activity GO:0046934 8.96 FGF8 FGFR1
4 1-phosphatidylinositol-3-kinase activity GO:0016303 8.62 FGF8 FGFR1

Sources for Hartsfield Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 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 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
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
Content
Loading form....