FTHS
MCID: FRN039
MIFTS: 38

Frank-Ter Haar Syndrome (FTHS)

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

Aliases & Classifications for Frank-Ter Haar Syndrome

MalaCards integrated aliases for Frank-Ter Haar Syndrome:

Name: Frank-Ter Haar Syndrome 57 75 37 13 40
Ter Haar Syndrome 57 53 75 73
Frank Ter Haar Syndrome 53 29 6
Borrone Dermatocardioskeletal Syndrome 57 75
Fths 57 75
Megalocornea, Multiple Skeletal Anomalies, and Developmental Delay 53
Melnick-Needles Syndrome, Autosomal Recessive, Formerly 57
Autosomal Recessive Melnick-Needles Syndrome 75
Borrone Di Rocco Crovato Syndrome 73

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive


HPO:

32
frank-ter haar syndrome:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Frank-Ter Haar Syndrome

OMIM : 57 The primary characteristics of the Frank-ter Haar syndrome are brachycephaly, wide fontanels, prominent forehead, hypertelorism, prominent eyes, macrocornea with or without glaucoma, full cheeks, small chin, bowing of the long bones, and flexion deformity of the fingers. Protruding, simple ears and prominent coccyx are also regarded as important diagnostic signs (summary by Maas et al., 2004). Borrone syndrome was described as a severe progressive multisystem disorder with features overlapping those of FTHS, including thick skin, acne conglobata, osteolysis, gingival hypertrophy, brachydactyly, camptodactyly, and mitral valve prolapse. Although it was initially thought to be a distinct phenotype, mutations in the FTHS-associated gene SH3PXD2B have been identified in patients diagnosed with Borrone syndrome. The earlier differential description was attributed to phenotypic variability as well as to differences in the ages at which patients were examined (Wilson et al., 2014). (249420)

MalaCards based summary : Frank-Ter Haar Syndrome, also known as ter haar syndrome, is related to borrone di rocco crovato syndrome and glaucoma 3, primary congenital, a. An important gene associated with Frank-Ter Haar Syndrome is SH3PXD2B (SH3 And PX Domains 2B), and among its related pathways/superpathways are Regulation of lipid metabolism Insulin signaling-generic cascades and EGF/EGFR Signaling Pathway. Affiliated tissues include eye, bone and skin, and related phenotypes are hypertelorism and low-set ears

NIH Rare Diseases : 53 Frank-Ter Haar syndrome is a rare inherited condition characterized by multiple skeletal abnormalities, developmental delay, and characteristic facial features (unusually large cornea, flattened back of the head, wide fontanels, prominent forehead, widely spaced eyes, prominent eyes, full cheeks, and small chin). Less than 30 cases have been reported worldwide. Protruding ears, prominent coccyx bone (or tail bone), and congenital heart defects are also frequently present. This condition is caused by mutations in the SH3PXD2B gene and is thought to be inherited in an autosomal recessive fashion.

UniProtKB/Swiss-Prot : 75 Frank-Ter Haar syndrome: A syndrome characterized by brachycephaly, wide fontanels, prominent forehead, hypertelorism, prominent eyes, macrocornea with or without glaucoma, full cheeks, small chin, bowing of the long bones and flexion deformity of the fingers.

Related Diseases for Frank-Ter Haar Syndrome

Diseases related to Frank-Ter Haar Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 borrone di rocco crovato syndrome 11.4
2 glaucoma 3, primary congenital, a 10.5
3 craniosynostosis 10.5
4 melnick-needles syndrome 10.3
5 opsismodysplasia 9.6 INPPL1 SH3PXD2B

Graphical network of the top 20 diseases related to Frank-Ter Haar Syndrome:



Diseases related to Frank-Ter Haar Syndrome

Symptoms & Phenotypes for Frank-Ter Haar Syndrome

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
hypertelorism
glaucoma
buphthalmos
large eyes
downslanting palpebral fissures
more
Chest Ribs Sternum Clavicles And Scapulae:
pectus excavatum
broad clavicles

Skeletal Pelvis:
hip dysplasia
decreased acetabular angle

Head And Neck Face:
full cheeks
micrognathia
coarse face

Skeletal Feet:
metatarsus adductus
talipes equinovarus

Head And Neck Nose:
broad nasal tip
anteverted nostrils
wide and flat nasal bridge

Head And Neck Teeth:
malocclusion

Growth Other:
growth retardation

Skin Nails Hair Skin:
acne conglobata
thick skin on face

Skeletal Spine:
tall vertebrae
anteriorly concave vertebrae
abnormal sternum
prominent coccyx

Head And Neck Ears:
low-set ears
simple ears
protruding ears
acne conglobata

Skeletal:
osteopenia
osteoporosis

Head And Neck Head:
prominent forehead
flat occiput
large anterior fontanel

Skeletal Skull:
wormian bones
delayed fontanel closure

Head And Neck Mouth:
wide mouth
high-arched palate
gingival hypertrophy

Skeletal Limbs:
cortical irregularity
metaphyseal flaring
shortened bowed long bones

Skeletal Hands:
short phalanges
flexion deformities of fingers

Growth Height:
short to normal stature

Cardiovascular Heart:
congenital heart defect (in some patients)
mitral valve anomaly

Neurologic Central Nervous System:
motor delay (in some patients)


Clinical features from OMIM:

249420

Human phenotypes related to Frank-Ter Haar Syndrome:

32 (show top 50) (show all 66)
# Description HPO Frequency HPO Source Accession
1 hypertelorism 32 hallmark (90%) HP:0000316
2 low-set ears 32 HP:0000369
3 pectus excavatum 32 HP:0000767
4 high palate 32 HP:0000218
5 osteopenia 32 HP:0000938
6 scoliosis 32 frequent (33%) HP:0002650
7 kyphosis 32 frequent (33%) HP:0002808
8 inguinal hernia 32 occasional (7.5%) HP:0000023
9 gingival overgrowth 32 frequent (33%) HP:0000212
10 coarse facial features 32 hallmark (90%) HP:0000280
11 mandibular prognathia 32 frequent (33%) HP:0000303
12 dental malocclusion 32 HP:0000689
13 hip dysplasia 32 HP:0001385
14 depressed nasal bridge 32 hallmark (90%) HP:0005280
15 bowing of the long bones 32 HP:0006487
16 aseptic necrosis 32 hallmark (90%) HP:0010885
17 wide nasal bridge 32 hallmark (90%) HP:0000431
18 joint stiffness 32 frequent (33%) HP:0001387
19 umbilical hernia 32 occasional (7.5%) HP:0001537
20 beaking of vertebral bodies 32 frequent (33%) HP:0004568
21 thick vermilion border 32 hallmark (90%) HP:0012471
22 osteoporosis 32 HP:0000939
23 prominent forehead 32 HP:0011220
24 full cheeks 32 HP:0000293
25 micrognathia 32 HP:0000347
26 delayed eruption of teeth 32 frequent (33%) HP:0000684
27 short long bone 32 HP:0003026
28 wormian bones 32 HP:0002645
29 genu recurvatum 32 frequent (33%) HP:0002816
30 acne 32 hallmark (90%) HP:0001061
31 metatarsus adductus 32 HP:0001840
32 growth delay 32 HP:0001510
33 protruding ear 32 frequent (33%) HP:0000411
34 motor delay 32 occasional (7.5%) HP:0001270
35 talipes equinovarus 32 HP:0001762
36 broad forehead 32 frequent (33%) HP:0000337
37 wide mouth 32 hallmark (90%) HP:0000154
38 short philtrum 32 hallmark (90%) HP:0000322
39 deeply set eye 32 hallmark (90%) HP:0000490
40 clinodactyly of the 5th finger 32 frequent (33%) HP:0004209
41 abnormality of the metacarpal bones 32 frequent (33%) HP:0001163
42 glaucoma 32 HP:0000501
43 mitral valve prolapse 32 hallmark (90%) HP:0001634
44 downslanted palpebral fissures 32 frequent (33%) HP:0000494
45 brachydactyly 32 hallmark (90%) HP:0001156
46 broad nasal tip 32 HP:0000455
47 buphthalmos 32 HP:0000557
48 flat occiput 32 HP:0005469
49 thickened skin 32 hallmark (90%) HP:0001072
50 high forehead 32 frequent (33%) HP:0000348

Drugs & Therapeutics for Frank-Ter Haar Syndrome

Search Clinical Trials , NIH Clinical Center for Frank-Ter Haar Syndrome

Genetic Tests for Frank-Ter Haar Syndrome

Genetic tests related to Frank-Ter Haar Syndrome:

# Genetic test Affiliating Genes
1 Frank Ter Haar Syndrome 29 SH3PXD2B

Anatomical Context for Frank-Ter Haar Syndrome

MalaCards organs/tissues related to Frank-Ter Haar Syndrome:

41
Eye, Bone, Skin, Heart

Publications for Frank-Ter Haar Syndrome

Articles related to Frank-Ter Haar Syndrome:

(show all 16)
# Title Authors Year
1
Anaesthesia and orphan diseases: difficult tracheal intubation in a child with Frank-ter Haar syndrome. ( 29870476 )
2018
2
Ophthalmic findings in Frank-ter Haar syndrome: report of a sibling pair. ( 29100834 )
2017
3
Identification of two novel SH3PXD2B gene mutations in Frank-Ter Haar syndrome by exome sequencing: Case report and review of the literature. ( 28694206 )
2017
4
Frank-ter Haar syndrome--additional findings? ( 26582053 )
2016
5
Accumulation of the PX domain mutant Frank-ter Haar syndrome protein Tks4 in aggresomes. ( 26183326 )
2015
6
Common dental features and craniofacial development of three siblings with Ter Haar syndrome. ( 24085649 )
2014
7
Congenital glaucoma as an ophthalmic manifestation of Frank-Ter Haar syndrome. ( 23709337 )
2013
8
Frank-Ter Haar syndrome in a newborn. ( 22037860 )
2012
9
Frank-ter Haar syndrome associated with sagittal craniosynostosis and raised intracranial pressure. ( 23140272 )
2012
10
Frank-ter Haar syndrome protein Tks4 regulates epidermal growth factor-dependent cell migration. ( 22829589 )
2012
11
Frank-Ter Haar Syndrome. ( 21453629 )
2011
12
Disruption of the podosome adaptor protein TKS4 (SH3PXD2B) causes the skeletal dysplasia, eye, and cardiac abnormalities of Frank-Ter Haar Syndrome. ( 20137777 )
2010
13
Frank-ter Haar syndrome with unusual clinical features. ( 19303467 )
2009
14
Mitral valve repair in a patient with Ter Haar Syndrome. ( 16948766 )
2006
15
Further delineation of Frank-ter Haar syndrome. ( 15523657 )
2004
16
Extended survival in a new case of ter Haar syndrome: further delineation of the syndrome. ( 9188664 )
1997

Variations for Frank-Ter Haar Syndrome

UniProtKB/Swiss-Prot genetic disease variations for Frank-Ter Haar Syndrome:

75
# Symbol AA change Variation ID SNP ID
1 SH3PXD2B p.Arg43Trp VAR_063764 rs267607046

ClinVar genetic disease variations for Frank-Ter Haar Syndrome:

6 (show top 50) (show all 246)
# Gene Variation Type Significance SNP ID Assembly Location
1 SH3PXD2B NM_001017995.2(SH3PXD2B): c.147dupT (p.Asp50Terfs) duplication Pathogenic rs794728005 GRCh38 Chromosome 5, 172422425: 172422425
2 SH3PXD2B NM_001017995.2(SH3PXD2B): c.147dupT (p.Asp50Terfs) duplication Pathogenic rs794728005 GRCh37 Chromosome 5, 171849429: 171849429
3 SH3PXD2B NM_001017995.2(SH3PXD2B): c.969delG (p.Arg324Glyfs) deletion Pathogenic/Likely pathogenic rs794728006 GRCh38 Chromosome 5, 172350406: 172350406
4 SH3PXD2B NM_001017995.2(SH3PXD2B): c.969delG (p.Arg324Glyfs) deletion Pathogenic/Likely pathogenic rs794728006 GRCh37 Chromosome 5, 171777410: 171777410
5 SH3PXD2B NM_001017995.2(SH3PXD2B): c.127C> T (p.Arg43Trp) single nucleotide variant Pathogenic rs267607046 GRCh37 Chromosome 5, 171849449: 171849449
6 SH3PXD2B NM_001017995.2(SH3PXD2B): c.127C> T (p.Arg43Trp) single nucleotide variant Pathogenic rs267607046 GRCh38 Chromosome 5, 172422445: 172422445
7 SH3PXD2B NM_001017995.2(SH3PXD2B): c.76-2A> C single nucleotide variant Pathogenic rs775217258 GRCh38 Chromosome 5, 172422498: 172422498
8 SH3PXD2B NM_001017995.2(SH3PXD2B): c.76-2A> C single nucleotide variant Pathogenic rs775217258 GRCh37 Chromosome 5, 171849502: 171849502
9 SH3PXD2B NM_001017995.2(SH3PXD2B): c.401+1G> A single nucleotide variant Pathogenic rs367543284 GRCh37 Chromosome 5, 171809039: 171809039
10 SH3PXD2B NM_001017995.2(SH3PXD2B): c.401+1G> A single nucleotide variant Pathogenic rs367543284 GRCh38 Chromosome 5, 172382035: 172382035
11 SH3PXD2B NM_001017995.2(SH3PXD2B): c.1063-8C> T single nucleotide variant Benign/Likely benign rs76931006 GRCh37 Chromosome 5, 171773273: 171773273
12 SH3PXD2B NM_001017995.2(SH3PXD2B): c.1063-8C> T single nucleotide variant Benign/Likely benign rs76931006 GRCh38 Chromosome 5, 172346269: 172346269
13 SH3PXD2B NM_001017995.2(SH3PXD2B): c.1063-9T> C single nucleotide variant Benign/Likely benign rs189684298 GRCh37 Chromosome 5, 171773274: 171773274
14 SH3PXD2B NM_001017995.2(SH3PXD2B): c.1063-9T> C single nucleotide variant Benign/Likely benign rs189684298 GRCh38 Chromosome 5, 172346270: 172346270
15 SH3PXD2B NM_001017995.2(SH3PXD2B): c.1188+1773_2733+6592del deletion Pathogenic GRCh37 Chromosome 5, 171758785: 171771367
16 SH3PXD2B NM_001017995.2(SH3PXD2B): c.1188+1773_2733+6592del deletion Pathogenic GRCh38 Chromosome 5, 172331781: 172344363
17 SH3PXD2B NM_001017995.2(SH3PXD2B): c.1062+15G> A single nucleotide variant Benign/Likely benign rs111572530 GRCh37 Chromosome 5, 171774272: 171774272
18 SH3PXD2B NM_001017995.2(SH3PXD2B): c.1062+15G> A single nucleotide variant Benign/Likely benign rs111572530 GRCh38 Chromosome 5, 172347268: 172347268
19 SH3PXD2B NM_001017995.2(SH3PXD2B): c.563-11T> C single nucleotide variant Benign rs2569232 GRCh38 Chromosome 5, 172358888: 172358888
20 SH3PXD2B NM_001017995.2(SH3PXD2B): c.563-11T> C single nucleotide variant Benign rs2569232 GRCh37 Chromosome 5, 171785892: 171785892
21 SH3PXD2B NM_001017995.2(SH3PXD2B): c.105C> T (p.Ser35=) single nucleotide variant Benign rs17074773 GRCh37 Chromosome 5, 171849471: 171849471
22 SH3PXD2B NM_001017995.2(SH3PXD2B): c.105C> T (p.Ser35=) single nucleotide variant Benign rs17074773 GRCh38 Chromosome 5, 172422467: 172422467
23 SH3PXD2B NM_001017995.2(SH3PXD2B): c.2456G> A (p.Arg819Gln) single nucleotide variant Uncertain significance rs200899339 GRCh37 Chromosome 5, 171765653: 171765653
24 SH3PXD2B NM_001017995.2(SH3PXD2B): c.2456G> A (p.Arg819Gln) single nucleotide variant Uncertain significance rs200899339 GRCh38 Chromosome 5, 172338649: 172338649
25 SH3PXD2B NM_001017995.2(SH3PXD2B): c.*4827T> A single nucleotide variant Benign rs3204110 GRCh37 Chromosome 5, 171760546: 171760546
26 SH3PXD2B NM_001017995.2(SH3PXD2B): c.*4827T> A single nucleotide variant Benign rs3204110 GRCh38 Chromosome 5, 172333542: 172333542
27 SH3PXD2B NM_001017995.2(SH3PXD2B): c.*3936G> A single nucleotide variant Likely benign rs74364058 GRCh37 Chromosome 5, 171761437: 171761437
28 SH3PXD2B NM_001017995.2(SH3PXD2B): c.*3936G> A single nucleotide variant Likely benign rs74364058 GRCh38 Chromosome 5, 172334433: 172334433
29 SH3PXD2B NM_001017995.2(SH3PXD2B): c.*3935C> T single nucleotide variant Uncertain significance rs886060409 GRCh37 Chromosome 5, 171761438: 171761438
30 SH3PXD2B NM_001017995.2(SH3PXD2B): c.*3935C> T single nucleotide variant Uncertain significance rs886060409 GRCh38 Chromosome 5, 172334434: 172334434
31 SH3PXD2B NM_001017995.2(SH3PXD2B): c.*3363T> C single nucleotide variant Uncertain significance rs530641139 GRCh38 Chromosome 5, 172335006: 172335006
32 SH3PXD2B NM_001017995.2(SH3PXD2B): c.*3363T> C single nucleotide variant Uncertain significance rs530641139 GRCh37 Chromosome 5, 171762010: 171762010
33 SH3PXD2B NM_001017995.2(SH3PXD2B): c.*3359C> T single nucleotide variant Uncertain significance rs886060411 GRCh38 Chromosome 5, 172335010: 172335010
34 SH3PXD2B NM_001017995.2(SH3PXD2B): c.*3359C> T single nucleotide variant Uncertain significance rs886060411 GRCh37 Chromosome 5, 171762014: 171762014
35 SH3PXD2B NM_001017995.2(SH3PXD2B): c.*3202C> T single nucleotide variant Uncertain significance rs180938966 GRCh38 Chromosome 5, 172335167: 172335167
36 SH3PXD2B NM_001017995.2(SH3PXD2B): c.*3202C> T single nucleotide variant Uncertain significance rs180938966 GRCh37 Chromosome 5, 171762171: 171762171
37 SH3PXD2B NM_001017995.2(SH3PXD2B): c.*2930dupG duplication Benign rs386405693 GRCh37 Chromosome 5, 171762443: 171762443
38 SH3PXD2B NM_001017995.2(SH3PXD2B): c.*2930dupG duplication Benign rs386405693 GRCh38 Chromosome 5, 172335439: 172335439
39 SH3PXD2B NM_001017995.2(SH3PXD2B): c.*2676G> A single nucleotide variant Uncertain significance rs553703806 GRCh37 Chromosome 5, 171762697: 171762697
40 SH3PXD2B NM_001017995.2(SH3PXD2B): c.*2676G> A single nucleotide variant Uncertain significance rs553703806 GRCh38 Chromosome 5, 172335693: 172335693
41 SH3PXD2B NM_001017995.2(SH3PXD2B): c.*2596A> G single nucleotide variant Benign rs889024 GRCh37 Chromosome 5, 171762777: 171762777
42 SH3PXD2B NM_001017995.2(SH3PXD2B): c.*2596A> G single nucleotide variant Benign rs889024 GRCh38 Chromosome 5, 172335773: 172335773
43 SH3PXD2B NM_001017995.2(SH3PXD2B): c.*1750T> C single nucleotide variant Likely benign rs3812019 GRCh37 Chromosome 5, 171763623: 171763623
44 SH3PXD2B NM_001017995.2(SH3PXD2B): c.*1750T> C single nucleotide variant Likely benign rs3812019 GRCh38 Chromosome 5, 172336619: 172336619
45 SH3PXD2B NM_001017995.2(SH3PXD2B): c.*1607A> G single nucleotide variant Uncertain significance rs537907753 GRCh37 Chromosome 5, 171763766: 171763766
46 SH3PXD2B NM_001017995.2(SH3PXD2B): c.*1607A> G single nucleotide variant Uncertain significance rs537907753 GRCh38 Chromosome 5, 172336762: 172336762
47 SH3PXD2B NM_001017995.2(SH3PXD2B): c.*1271_*1272insG insertion Benign rs5873310 GRCh37 Chromosome 5, 171764101: 171764102
48 SH3PXD2B NM_001017995.2(SH3PXD2B): c.*1271_*1272insG insertion Benign rs5873310 GRCh38 Chromosome 5, 172337097: 172337098
49 SH3PXD2B NM_001017995.2(SH3PXD2B): c.*1253A> G single nucleotide variant Benign rs869367 GRCh37 Chromosome 5, 171764120: 171764120
50 SH3PXD2B NM_001017995.2(SH3PXD2B): c.*1253A> G single nucleotide variant Benign rs869367 GRCh38 Chromosome 5, 172337116: 172337116

Expression for Frank-Ter Haar Syndrome

Search GEO for disease gene expression data for Frank-Ter Haar Syndrome.

Pathways for Frank-Ter Haar Syndrome

GO Terms for Frank-Ter Haar Syndrome

Biological processes related to Frank-Ter Haar Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 positive regulation of gene expression GO:0010628 8.62 EGF SH3PXD2B

Molecular functions related to Frank-Ter Haar Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 SH2 domain binding GO:0042169 8.62 INPPL1 SH3PXD2B

Sources for Frank-Ter Haar Syndrome

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11 DGIdb
17 ExPASy
19 FMA
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32 HPO
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45 MESH via Orphanet
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57 OMIM
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62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
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71 TGDB
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74 UMLS via Orphanet
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