HRTFDS
MCID: HRT030
MIFTS: 45

Hartsfield Syndrome (HRTFDS)

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

Aliases & Classifications for Hartsfield Syndrome

MalaCards integrated aliases for Hartsfield Syndrome:

Name: Hartsfield Syndrome 57 24 25 59 74 37 29 6 40
Holoprosencephaly, Ectrodactyly, and Bilateral Cleft Lip/palate 57 25
Hrtfds 57 74
Holoprosencephaly, Ectrodactyly, and Bilateral Cleft Lip-Palate 72
Holoprosencephaly, Ectrodactyly and Bilateral Cleft Lip/palate 74
Holoprosencephaly, Hypertelorism, and Ectrodactyly Syndrome 25
Holoprosencephaly-Ectrodactyly-Cleft Lip/palate Syndrome 59
Holoprosencephaly and Split Hand/foot Syndrome 25
Hartsfield-Bixler-Demyer Syndrome 25
Hhes 25

Characteristics:

Orphanet epidemiological data:

59
hartsfield syndrome
Inheritance: Autosomal dominant,Autosomal recessive; Prevalence: <1/1000000 (Worldwide);

OMIM:

57
Inheritance:
autosomal dominant


HPO:

32
hartsfield syndrome:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

OMIM 57 615465
KEGG 37 H01850
ICD10 via Orphanet 34 Q87.8
UMLS via Orphanet 73 C1845146
Orphanet 59 ORPHA2117
MedGen 42 C1845146
UMLS 72 C1845146

Summaries for Hartsfield Syndrome

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. During early development before birth, the brain normally divides into two halves, the right and left hemispheres. Holoprosencephaly occurs when the brain fails to divide properly. In the most severe forms of holoprosencephaly, the brain does not divide at all. These affected individuals have one central eye (cyclopia) and a tubular nasal structure (proboscis) located above the eye. Most babies with severe holoprosencephaly die before birth or soon after. In less severe cases of holoprosencephaly, the brain is partially divided. The life expectancy of these affected individuals depends on the severity of signs and symptoms. People with Hartsfield syndrome often have other brain abnormalities associated with holoprosencephaly. Affected individuals may have a malfunctioning pituitary, which is a gland located at the base of the brain that produces several hormones. Because pituitary dysfunction leads to the partial or complete absence of these hormones, it can cause a variety of disorders. These include diabetes insipidus, which disrupts the balance between fluid intake and urine excretion; a shortage (deficiency) of growth hormone, leading to slow or delayed growth; and hypogonadotropic hypogonadism, which affects the production of hormones that direct sexual development. Dysfunction in other parts of the brain can cause seizures, feeding difficulties, and problems regulating body temperature and sleep patterns. People with Hartsfield syndrome have delayed development that ranges from mild to severe. The other hallmark feature of Hartsfield syndrome is ectrodactyly. Ectrodactyly is a deep split in the hands, feet, or both, with missing fingers or toes and partial fusion of the remaining digits. It can affect the hands and feet on one or both sides. Other features that have been described in people with Hartsfield syndrome include premature fusion of certain bones of the skull (craniosynostosis), heart defects, abnormalities of the bones of the spine (vertebrae), and abnormal genitalia. Some affected individuals have distinctive facial features, including eyes that are widely spaced (hypertelorism) or closely spaced (hypotelorism), ears that are abnormally small or unusually shaped, and a split in the lip (cleft lip) with or without an opening in the roof of the mouth (cleft palate).

MalaCards based summary : Hartsfield Syndrome, also known as holoprosencephaly, ectrodactyly, and bilateral cleft lip/palate, is related to holoprosencephaly and hypogonadotropic hypogonadism. An important gene associated with Hartsfield Syndrome is FGFR1 (Fibroblast Growth Factor Receptor 1), and among its related pathways/superpathways are Downstream signaling of activated FGFR2 and Pathways in cancer. Affiliated tissues include pituitary, bone and brain, and related phenotypes are hypertelorism and ptosis

OMIM : 57 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)

KEGG : 37
Harstfield syndrome is the rare and unique association of holoprosencephaly (HPE) and ectrodactyly, with or without cleft lip and palate, and variable additional features. HPE and ectrodactyly can occur, separately, as part of numerous syndromes, but the co-occurrence of these two malformations has only been reported only in a very limited number. Additional signs such as craniosynostosis, hypertelorism or hypotelorism, microphthalmia, abnormal ears, radial agenesis, genital anomalies, severe psychomotor retardation, and hypothalamic-pituitary dysfunction have been observed. Dominant or recessive FGFR1 mutations are responsible for Hartsfield syndrome.

UniProtKB/Swiss-Prot : 74 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

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

(show all 49)
# Related Disease Score Top Affiliating Genes
1 holoprosencephaly 30.3 FGFR1 FGF8
2 hypogonadotropic hypogonadism 30.1 FGFR1 FGF8
3 hypogonadism 30.0 FGFR1 FGF8
4 lobar holoprosencephaly 29.7 FGFR1 FGF8
5 kallmann syndrome 29.0 FGFR1 FGF8
6 idiopathic hemiconvulsion-hemiplegia syndrome 12.2
7 holoprosencephaly ectrodactyly cleft lip palate 11.6
8 hemiplegia 10.5
9 epilepsy 10.5
10 split-hand/foot malformation 1 10.5
11 isolated split hand-split foot malformation 10.5
12 cleft lip 10.4
13 cleft lip/palate 10.4
14 hypogonadotropism 10.3
15 pertussis 10.2
16 tetanus 10.2
17 diphtheria 10.2
18 triiodothyronine receptor auxiliary protein 10.1
19 cystic fibrosis 10.1
20 cyanosis, transient neonatal 10.1
21 hydrops, lactic acidosis, and sideroblastic anemia 10.1
22 visual epilepsy 10.1
23 urticaria 10.1
24 status epilepticus 10.1
25 hypotonia 10.1
26 seizure disorder 10.1
27 gastroesophageal reflux 10.0
28 hypogonadotropic hypogonadism 7 with or without anosmia 10.0
29 chromosome 2q35 duplication syndrome 10.0
30 corpus callosum, agenesis of 10.0
31 polydactyly 10.0
32 split hand-foot malformation 10.0
33 calcinosis 10.0
34 diabetes insipidus 10.0
35 microcephaly 10.0
36 isolated gonadotropin-releasing hormone deficiency 10.0
37 absence of septum pellucidum 10.0
38 nonsyndromic holoprosencephaly 10.0
39 spasticity 10.0
40 microform holoprosencephaly 9.7 FGFR1 FGF8
41 normosmic congenital hypogonadotropic hypogonadism 9.7 FGFR1 FGF8
42 semilobar holoprosencephaly 9.7 FGFR1 FGF8
43 thanatophoric dysplasia, type i 9.7 FGFR1 FGF8
44 thrombocytopenia-absent radius syndrome 9.6 FGFR1 FGF8
45 muenke syndrome 9.6 FGFR1 FGF8
46 charge syndrome 9.6 FGFR1 FGF8
47 lacrimoauriculodentodigital syndrome 9.5 FGFR1 FGF8
48 pfeiffer syndrome 9.5 FGFR1 FGF8
49 craniosynostosis 9.4 FGFR1 FGF8

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



Diseases related to Hartsfield Syndrome

Symptoms & Phenotypes for Hartsfield Syndrome

Human phenotypes related to Hartsfield Syndrome:

59 32 (show all 37)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hypertelorism 59 32 hallmark (90%) Very frequent (99-80%) HP:0000316
2 ptosis 59 32 hallmark (90%) Very frequent (99-80%) HP:0000508
3 respiratory insufficiency 59 32 hallmark (90%) Very frequent (99-80%) HP:0002093
4 depressed nasal bridge 59 32 hallmark (90%) Very frequent (99-80%) HP:0005280
5 cleft palate 59 32 hallmark (90%) Very frequent (99-80%) HP:0000175
6 intrauterine growth retardation 59 32 hallmark (90%) Very frequent (99-80%) HP:0001511
7 telecanthus 59 32 hallmark (90%) Very frequent (99-80%) HP:0000506
8 non-midline cleft lip 59 32 hallmark (90%) Very frequent (99-80%) HP:0100335
9 microphthalmia 59 32 hallmark (90%) Very frequent (99-80%) HP:0000568
10 low-set, posteriorly rotated ears 59 32 hallmark (90%) Very frequent (99-80%) HP:0000368
11 downslanted palpebral fissures 59 32 hallmark (90%) Very frequent (99-80%) HP:0000494
12 craniosynostosis 59 32 occasional (7.5%) Very frequent (99-80%) HP:0001363
13 aplasia/hypoplasia of the corpus callosum 59 32 hallmark (90%) Very frequent (99-80%) HP:0007370
14 encephalocele 59 32 hallmark (90%) Very frequent (99-80%) HP:0002084
15 lobar holoprosencephaly 59 32 hallmark (90%) Very frequent (99-80%) HP:0006870
16 split hand 59 32 frequent (33%) Frequent (79-30%) HP:0001171
17 aplasia/hypoplasia of the radius 59 32 frequent (33%) Frequent (79-30%) HP:0006501
18 low-set ears 32 HP:0000369
19 agenesis of corpus callosum 32 HP:0001274
20 global developmental delay 32 HP:0001263
21 microcephaly 32 HP:0000252
22 neonatal hypotonia 32 HP:0001319
23 epicanthus 32 HP:0000286
24 cryptorchidism 32 HP:0000028
25 hypospadias 32 HP:0000047
26 diabetes insipidus 32 HP:0000873
27 micropenis 32 HP:0000054
28 cleft upper lip 32 HP:0000204
29 hypotelorism 32 HP:0000601
30 wide nose 32 HP:0000445
31 ectrodactyly 32 HP:0100257
32 posteriorly rotated ears 32 HP:0000358
33 syndactyly 32 HP:0001159
34 gonadotropin deficiency 32 HP:0008213
35 hypernatremia 32 HP:0003228
36 hypoplasia of the frontal bone 32 HP:0005466
37 psychomotor retardation 32 HP:0025356

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
hypertelorism
hypotelorism
epicanthal folds

Head And Neck Head:
microcephaly

Genitourinary Internal Genitalia Male:
cryptorchidism

Endocrine Features:
diabetes insipidus
gonadotropin deficiency

Skeletal Hands:
ectrodactyly
syndactyly

Laboratory Abnormalities:
hypernatremia

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

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

Head And Neck Mouth:
cleft palate
cleft lip

Genitourinary External Genitalia Male:
hypospadias
small penis

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

Skeletal Feet:
ectrodactyly
syndactyly

Head And Neck Nose:
broad nose

Clinical features from OMIM:

615465

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:

# Genetic test Affiliating Genes
1 Hartsfield Syndrome 29 FGFR1

Anatomical Context for Hartsfield Syndrome

MalaCards organs/tissues related to Hartsfield Syndrome:

41
Pituitary, Bone, Brain, Heart, Eye

Publications for Hartsfield Syndrome

Articles related to Hartsfield Syndrome:

(show all 30)
# Title Authors PMID Year
1
FGFR1 mutations cause Hartsfield syndrome, the unique association of holoprosencephaly and ectrodactyly. 38 4 8 71
23812909 2013
2
Hartsfield holoprosencephaly-ectrodactyly syndrome in five male patients: further delineation and review. 38 8 71
19504604 2009
3
Hartsfield Syndrome 38 71
26937548 2016
4
Detection of gonadal mosaicism in Hartsfield syndrome by next generation sequencing. 38 4
27604603 2016
5
Hyperosmia, ectrodactyly, mild intellectual disability, and other defects in a male patient with an X-linked partial microduplication and overexpression of the KAL1 gene. 38 4
25339597 2015
6
Novel de novo heterozygous FGFR1 mutation in two siblings with Hartsfield syndrome: a case of gonadal mosaicism. 38 4
24888332 2014
7
Microduplication of Xq24 and Hartsfield syndrome with holoprosencephaly, ectrodactyly, and clefting. 38 4
22887648 2012
8
Holoprosencephaly, ectrodactyly, and bilateral cleft of lip and palate: exclusion of SHH, TGIF, SIX3, GLI2, TP73L, and DHCR7 as candidate genes. 8
19449411 2009
9
Holoprosencephaly, bilateral cleft lip and palate and ectrodactyly: another case and follow up. 8
14564207 2003
10
Holoprosencephaly Overview 71
20301702 2000
11
Holoprosencephaly, telecanthus and ectrodactyly: a second case. 8
1342859 1992
12
Congenital hypogonadotropic hypogonadism with split hand/foot malformation: a clinical entity with a high frequency of FGFR1 mutations. 4
25394172 2015
13
Kallmann syndrome with FGFR1 and KAL1 mutations detected during fetal life. 4
26051373 2015
14
Congenital hypogonadotropic hypogonadism during childhood: presentation and genetic analyses in 46 boys. 4
24204987 2013
15
Mechanisms of FGFR-mediated carcinogenesis. 4
22273505 2012
16
Evidence that FGFR1 loss-of-function mutations may cause variable skeletal malformations in patients with Kallmann syndrome. 4
23154428 2012
17
Holoprosencephaly and ectrodactyly: Report of three new patients and review of the literature. 4
20104609 2010
18
FGFR1 mutations in Kallmann syndrome. 4
20389085 2010
19
Extended mutational analyses of FGFR1 in osteoglophonic dysplasia. 4
16470795 2006
20
Development of midline cell types and commissural axon tracts requires Fgfr1 in the cerebrum. 4
16309667 2006
21
The structure and function of vertebrate fibroblast growth factor receptor 1. 4
12141425 2002
22
Holoprosencephaly and split hand/foot: an additional case with this rare association. 4
11666003 2001
23
Association of holoprosencephaly, ectrodactyly, cleft lip/cleft palate and hypertelorism: a possible third case. 4
9689997 1998
24
Mutations in FGFR1 and FGFR2 cause familial and sporadic Pfeiffer syndrome. 4
7795583 1995
25
A novel dominant-negative FGFR1 variant causes Hartsfield syndrome by deregulating RAS/ERK1/2 pathway. 38
30787447 2019
26
The Use of Variant Maps to Explore Domain-Specific Mutations of FGFR1. 38
28825856 2017
27
Otorhinolaryngologic manifestations of Hartsfield syndrome: Case series and review of literature. 38
28583501 2017
28
Hartsfield syndrome associated with a novel heterozygous missense mutation in FGFR1 and incorporating tumoral calcinosis. 38
27170295 2016
29
Dominant-negative kinase domain mutations in FGFR1 can explain the clinical severity of Hartsfield syndrome. 38
26931467 2016
30
Novel heterozygous mutation in the extracellular domain of FGFR1 associated with Hartsfield syndrome. 38
27790375 2016

Variations for Hartsfield Syndrome

ClinVar genetic disease variations for Hartsfield Syndrome:

6 (show all 19)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 FGFR1 NM_023110.2(FGFR1): c.1604T> A (p.Met535Lys) single nucleotide variant Pathogenic rs1554551667 8:38274883-38274883 8:38417365-38417365
2 FGFR1 NM_023110.2(FGFR1): c.1921G> A (p.Asp641Asn) single nucleotide variant Pathogenic rs1554548253 8:38272353-38272353 8:38414835-38414835
3 FGFR1 NM_023110.2(FGFR1): c.1869C> G (p.Asp623Glu) single nucleotide variant Pathogenic rs780009859 8:38272405-38272405 8:38414887-38414887
4 FGFR1 NM_023110.2(FGFR1): c.2174G> A (p.Cys725Tyr) single nucleotide variant Pathogenic rs398122945 8:38271682-38271682 8:38414164-38414164
5 FGFR1 NM_023110.2(FGFR1): c.494T> C (p.Leu165Ser) single nucleotide variant Pathogenic rs397515481 8:38285566-38285566 8:38428048-38428048
6 FGFR1 NM_023110.2(FGFR1): c.1867G> T (p.Asp623Tyr) single nucleotide variant Pathogenic rs398122946 8:38272407-38272407 8:38414889-38414889
7 FGFR1 NM_023110.2(FGFR1): c.1460G> A (p.Gly487Asp) single nucleotide variant Pathogenic rs515726224 8:38275480-38275480 8:38417962-38417962
8 FGFR1 NM_023110.2(FGFR1): c.1884T> G (p.Asn628Lys) single nucleotide variant Pathogenic rs869025672 8:38272390-38272390 8:38414872-38414872
9 FGFR1 NM_023110.2(FGFR1): c.572T> C (p.Leu191Ser) single nucleotide variant Pathogenic rs869025669 8:38285488-38285488 8:38427970-38427970
10 FGFR1 NM_023110.2(FGFR1): c.1996T> C (p.Trp666Arg) single nucleotide variant Pathogenic 8:38272129-38272129 8:38414611-38414611
11 FGFR1 NM_023110.2(FGFR1): c.1881G> C (p.Arg627Ser) single nucleotide variant Pathogenic 8:38272393-38272393 8:38414875-38414875
12 FGFR1 NM_023110.2(FGFR1): c.1601_1603TGA[1] (p.Met535del) short repeat Pathogenic/Likely pathogenic rs1554551657 8:38274881-38274883 8:38417363-38417365
13 FGFR1 NM_023110.2(FGFR1): c.1468G> C (p.Gly490Arg) single nucleotide variant Pathogenic/Likely pathogenic rs869025670 8:38275472-38275472 8:38417954-38417954
14 FGFR1 NM_023110.2(FGFR1): c.1097C> T (p.Pro366Leu) single nucleotide variant Likely pathogenic rs121909641 8:38277238-38277238 8:38419720-38419720
15 FGFR1 NM_023110.2(FGFR1): c.1454G> T (p.Gly485Val) single nucleotide variant Likely pathogenic rs876661332 8:38275486-38275486 8:38417968-38417968
16 FGFR1 NM_023110.2(FGFR1): c.1880G> C (p.Arg627Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs869025671 8:38272394-38272394 8:38414876-38414876
17 FGFR1 NM_023110.2(FGFR1): c.899T> C (p.Ile300Thr) single nucleotide variant Uncertain significance rs121909633 8:38282064-38282064 8:38424546-38424546
18 FGFR1 NM_023110.2(FGFR1): c.454G> A (p.Ala152Thr) single nucleotide variant Benign rs1033377277 8:38285606-38285606 8:38428088-38428088
19 FGFR1 NM_023110.2(FGFR1): c.304G> A (p.Val102Ile) single nucleotide variant Benign rs55642501 8:38287254-38287254 8:38429736-38429736

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

74
# 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

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 25)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.35 FGFR1 FGF8
2 12.33 FGFR1 FGF8
3 12.26 FGFR1 FGF8
4
Show member pathways
12.25 FGFR1 FGF8
5
Show member pathways
12.22 FGFR1 FGF8
6
Show member pathways
12.21 FGFR1 FGF8
7
Show member pathways
12.19 FGFR1 FGF8
8
Show member pathways
12.18 FGFR1 FGF8
9 12.1 FGFR1 FGF8
10
Show member pathways
12.04 FGFR1 FGF8
11
Show member pathways
11.96 FGFR1 FGF8
12
Show member pathways
11.9 FGFR1 FGF8
13
Show member pathways
11.87 FGFR1 FGF8
14
Show member pathways
11.81 FGFR1 FGF8
15
Show member pathways
11.8 FGFR1 FGF8
16
Show member pathways
11.73 FGFR1 FGF8
17
Show member pathways
11.66 FGFR1 FGF8
18
Show member pathways
11.56 FGFR1 FGF8
19
Show member pathways
11.52 FGFR1 FGF8
20 11.18 FGFR1 FGF8
21 11.16 FGFR1 FGF8
22
Show member pathways
10.91 FGFR1 FGF8
23 10.53 FGFR1 FGF8
24 10.52 FGFR1 FGF8
25 10.4 FGFR1 FGF8

GO Terms for Hartsfield Syndrome

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

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 positive regulation of cell proliferation GO:0008284 9.49 FGFR1 FGF8
2 MAPK cascade GO:0000165 9.46 FGFR1 FGF8
3 positive regulation of protein kinase B signaling GO:0051897 9.4 FGFR1 FGF8
4 lung development GO:0030324 9.37 FGFR1 FGF8
5 fibroblast growth factor receptor signaling pathway GO:0008543 9.32 FGFR1 FGF8
6 inner ear morphogenesis GO:0042472 9.26 FGFR1 FGF8
7 positive regulation of ERK1 and ERK2 cascade GO:0070374 9.18 FGF8
8 generation of neurons GO:0048699 9.16 FGFR1 FGF8
9 peptidyl-tyrosine phosphorylation GO:0018108 9.13 FGFR1
10 branching involved in salivary gland morphogenesis GO:0060445 8.96 FGFR1 FGF8
11 organ induction GO:0001759 8.62 FGFR1 FGF8

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

# Name GO ID Score Top Affiliating Genes
1 protein tyrosine kinase activity GO:0004713 8.32 FGFR1

Sources for Hartsfield Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 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 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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