MCID: WLF002
MIFTS: 54

Wolf-Hirschhorn Syndrome

Categories: Rare diseases, Genetic diseases, Smell/Taste diseases, Ear diseases

Aliases & Classifications for Wolf-Hirschhorn Syndrome

MalaCards integrated aliases for Wolf-Hirschhorn Syndrome:

Name: Wolf-Hirschhorn Syndrome 53 12 72 23 49 24 13 41 14 69
Pitt-Rogers-Danks Syndrome 53 12 49 69
4p Deletion Syndrome 12 24 36
Wittwer Syndrome 53 49 69
4p- Syndrome 23 49 24
Whs 53 49 24
Chromosome 4p16.3 Deletion Syndrome 53 12
Pitt Syndrome 53 12
Monosomy 4p 23 24
Microcephaly, Iugr, Hypertelorism, Ptosis, Iris Coloboma, Hooked Nose, External Ear Dysplasia, Psychomotor Retardation 49
Pitt-Rogers-Danks Syndrome; Prds 53
Chromosome 4p Deletion Syndrome 24
Chromosome 4 Short Arm Deletion 69
Chromosome 4p Syndrome 49
Chromosome 4p Monosomy 24
Telomeric Deletion 4p 49
Partial Monosomy 4p 24
Distal Deletion 4p 49
Distal Monosomy 4p 49
Del Syndrome 24
Wolf Syndrome 49
4p Syndrome 49
Prds 53

Characteristics:

OMIM:

53
Inheritance:
isolated cases

Miscellaneous:
contiguous gene deletion syndrome
sex ratio 2 females to 1 male
de novo deletions in 87% of patients (preferentially paternally derived)
13% of cases secondary to familial translocation (often maternally derived)
size of deletion varies from cytogenetically visible deletions to undetectable cytogenetic deletions
fish can be used to detect deletions of 4p16.3, the critical region for the phenotype
approximately 35% of patients die during the first 2 years of life
the frequency is estimated at 1/20,000 to 1/50,000 births


HPO:

31
wolf-hirschhorn syndrome:
Inheritance autosomal dominant inheritance sporadic


Classifications:



Summaries for Wolf-Hirschhorn Syndrome

NIH Rare Diseases : 49 Wolf-Hirschhorn syndrome (WHS) is a genetic disorder that affects many parts of the body. The major features include a characteristic facial appearance, delayed growth and development, intellectual disability, low muscle tone (hypotonia), and seizures. Other features may include skeletal abnormalities, congenital heart defects, hearing loss, urinary tract malformations, and/or structural brain abnormalities. WHS is caused by a missing piece (deletion) of genetic material near the end of the short (p) arm of chromosome 4 (written as 4p-). The size of the deletion varies among people with WHS, and studies suggest larger deletions tend to result in more severe features. Most cases of WHS are not inherited, but some cases are inherited from a parent who does not have WHS. Treatment depends on the symptoms. Last updated: 4/28/2017

MalaCards based summary : Wolf-Hirschhorn Syndrome, also known as pitt-rogers-danks syndrome, is related to chromosome 4p deletion and chromosomal deletion syndrome, and has symptoms including ataxia, seizures and hypertelorism. An important gene associated with Wolf-Hirschhorn Syndrome is NSD2 (Nuclear Receptor Binding SET Domain Protein 2), and among its related pathways/superpathways are Lysine degradation and E-cadherin signaling in the nascent adherens junction. Affiliated tissues include heart, brain and eye, and related phenotypes are craniofacial and digestive/alimentary

OMIM : 53 Wolf-Hirschhorn syndrome is a congenital malformation syndrome characterized by pre- and postnatal growth deficiency, developmental disability of variable degree, characteristic craniofacial features ('Greek warrior helmet' appearance of the nose, high forehead, prominent glabella, hypertelorism, high-arched eyebrows, protruding eyes, epicanthal folds, short philtrum, distinct mouth with downturned corners, and micrognathia), and a seizure disorder (Battaglia et al., 2008). (194190)

Genetics Home Reference : 24 Wolf-Hirschhorn syndrome is a condition that affects many parts of the body. The major features of this disorder include a characteristic facial appearance, delayed growth and development, intellectual disability, and seizures.

GeneReviews: NBK1183

Related Diseases for Wolf-Hirschhorn Syndrome

Diseases related to Wolf-Hirschhorn Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 81)
# Related Disease Score Top Affiliating Genes
1 chromosome 4p deletion 32.2 LETM1 NSD2 WFS1
2 chromosomal deletion syndrome 29.3 LETM1 NELFA NSD2
3 wieacker-wolff syndrome 11.5
4 retinal dysplasia, primary 11.4
5 aplasia cutis congenita, nonsyndromic 11.3
6 oligomeganephronic renal hypoplasia 11.3
7 woolly hair, autosomal dominant 11.2
8 hypotrichosis 8 11.1
9 hypotrichosis 7 11.1
10 chromosome 3p deletion 10.6
11 chromosome 3p- syndrome 10.6
12 distal chromosome 18q deletion syndrome 10.6
13 proximal chromosome 18q deletion syndrome 10.6
14 epilepsy 10.4
15 diaphragmatic hernia, congenital 10.3
16 malignant hyperthermia 10.2
17 chromosome 4p duplication 10.2
18 xp22.13p22.2 duplication syndrome 10.2
19 xq12-q13.3 duplication syndrome 10.2
20 aging 10.1
21 hemangioma 10.1
22 hepatitis 10.1
23 hypospadias 10.1
24 cleft lip 10.1
25 ring chromosome 4 10.1
26 splenomegaly 10.1
27 wandering spleen 10.1
28 split hand 10.1
29 coloboma of macula 10.0
30 polykaryocytosis inducer 10.0
31 vesicoureteral reflux 1 10.0
32 meier-gorlin syndrome 1 10.0
33 hypoplastic left heart syndrome 1 10.0
34 myeloma, multiple 10.0
35 neuroblastoma 10.0
36 body mass index quantitative trait locus 11 10.0
37 body mass index quantitative trait locus 9 10.0
38 branchiootic syndrome 1 10.0
39 body mass index quantitative trait locus 8 10.0
40 body mass index quantitative trait locus 4 10.0
41 body mass index quantitative trait locus 10 10.0
42 body mass index quantitative trait locus 7 10.0
43 cavitary optic disc anomalies 10.0
44 body mass index quantitative trait locus 12 10.0
45 body mass index quantitative trait locus 14 10.0
46 body mass index quantitative trait locus 18 10.0
47 diabetes mellitus 10.0
48 hypoplastic left heart syndrome 10.0
49 opitz-gbbb syndrome 10.0
50 lymphoma 10.0

Graphical network of the top 20 diseases related to Wolf-Hirschhorn Syndrome:



Diseases related to Wolf-Hirschhorn Syndrome

Symptoms & Phenotypes for Wolf-Hirschhorn Syndrome

Symptoms via clinical synopsis from OMIM:

53
Neurologic Central Nervous System:
seizures
hydrocephalus
absent septum pellucidum
hypotonia
enlarged ventricles
more
Endocrine Features:
precocious puberty

Skeletal Spine:
scoliosis
kyphosis
sacral dimple
fused vertebrae
sacral sinus
more
Head And Neck Head:
microcephaly
cranial asymmetry
posterior midline scalp defects

Head And Neck Mouth:
cleft palate
downturned corners of mouth
cleft lip
short upper lip

Genitourinary Internal Genitalia Male:
cryptorchidism

Head And Neck Neck:
webbed neck

Cardiovascular Heart:
atrial septal defect
ventricular septal defect

Skeletal Pelvis:
hip dislocation
absence of pubic rami

Head And Neck Teeth:
hypodontia

Skeletal Limbs:
radioulnar synostosis
thin limbs

Head And Neck Ears:
hearing loss
preauricular tags
preauricular pits
narrow external auditory canals

Chest RibsSternum Clavicles And Scapulae:
fused ribs
sternal ossification center abnormalities

Skeletal Hands:
transverse palmar creases
accessory proximal metacarpal ossification centers

Abdomen Biliary Tract:
absence of gallbladder

Laboratory Abnormalities:
hemizygous deletion at 4p16.3

Head And Neck Eyes:
hypertelorism
ptosis
nystagmus
strabismus
iris coloboma
more
Growth Other:
failure to thrive
marked intrauterine growth retardation

Head And Neck Nose:
wide nasal bridge
beaked nose

Abdomen Gastroin testinal:
gastroesophageal reflux
malrotation of small bowel

Head And Neck Face:
micrognathia
short philtrum
high forehead
prominent glabella

Skeletal Feet:
metatarsus adductus
talipes equinovarus
polydactyly

Skin Nails Hair Hair:
low posterior hairline
high-arched eyebrows
sparse medial eyebrows

Skin Nails Hair Nails:
hyperconvex fingernails

Genitourinary External Genitalia Male:
hypospadias

Skin Nails Hair Skin:
sacral dimple
transverse palmar creases
posterior midline scalp defects

Abdomen Spleen:
accessory spleen

Skeletal:
delayed bone age

Growth Weight:
low birth weight

Prenatal Manifestations Movement:
decreased fetal activity

Genitourinary Internal Genitalia Female:
absent uterus


Clinical features from OMIM:

194190

Human phenotypes related to Wolf-Hirschhorn Syndrome:

31 (show top 50) (show all 116)
# Description HPO Frequency HPO Source Accession
1 ataxia 31 hallmark (90%) HP:0001251
2 seizures 31 frequent (33%) HP:0001250
3 hypertelorism 31 frequent (33%) HP:0000316
4 agenesis of corpus callosum 31 occasional (7.5%) HP:0001274
5 frontal bossing 31 hallmark (90%) HP:0002007
6 hydrocephalus 31 occasional (7.5%) HP:0000238
7 ptosis 31 frequent (33%) HP:0000508
8 nystagmus 31 frequent (33%) HP:0000639
9 precocious puberty 31 HP:0000826
10 intellectual disability 31 HP:0001249
11 muscular hypotonia 31 hallmark (90%) HP:0001252
12 failure to thrive 31 frequent (33%) HP:0001508
13 eeg abnormality 31 very rare (1%) HP:0002353
14 scoliosis 31 frequent (33%) HP:0002650
15 kyphosis 31 frequent (33%) HP:0002808
16 hearing impairment 31 frequent (33%) HP:0000365
17 chronic otitis media 31 occasional (7.5%) HP:0000389
18 global developmental delay 31 hallmark (90%) HP:0001263
19 hip dysplasia 31 occasional (7.5%) HP:0001385
20 recurrent respiratory infections 31 occasional (7.5%) HP:0002205
21 delayed skeletal maturation 31 frequent (33%) HP:0002750
22 wide nasal bridge 31 frequent (33%) HP:0000431
23 microtia 31 hallmark (90%) HP:0008551
24 microcephaly 31 frequent (33%) HP:0000252
25 sensorineural hearing impairment 31 very rare (1%) HP:0000407
26 optic atrophy 31 frequent (33%) HP:0000648
27 short stature 31 frequent (33%) HP:0004322
28 gastroesophageal reflux 31 HP:0002020
29 retinopathy 31 occasional (7.5%) HP:0000488
30 stereotypy 31 frequent (33%) HP:0000733
31 osteoporosis 31 occasional (7.5%) HP:0000939
32 decreased muscle mass 31 hallmark (90%) HP:0003199
33 abnormality of the gallbladder 31 occasional (7.5%) HP:0005264
34 intellectual disability, severe 31 hallmark (90%) HP:0010864
35 immunodeficiency 31 very rare (1%) HP:0002721
36 abnormality of movement 31 occasional (7.5%) HP:0100022
37 cleft palate 31 occasional (7.5%) HP:0000175
38 micrognathia 31 frequent (33%) HP:0000347
39 strabismus 31 frequent (33%) HP:0000486
40 epicanthus 31 frequent (33%) HP:0000286
41 megalocornea 31 occasional (7.5%) HP:0000485
42 dolichocephaly 31 hallmark (90%) HP:0000268
43 abnormal form of the vertebral bodies 31 frequent (33%) HP:0003312
44 cryptorchidism 31 very rare (1%) HP:0000028
45 metatarsus adductus 31 HP:0001840
46 intrauterine growth retardation 31 hallmark (90%) HP:0001511
47 aplasia/hypoplasia of the nipples 31 occasional (7.5%) HP:0006709
48 webbed neck 31 occasional (7.5%) HP:0000465
49 low posterior hairline 31 hallmark (90%) HP:0002162
50 atrial septal defect 31 very rare (1%) HP:0001631

UMLS symptoms related to Wolf-Hirschhorn Syndrome:


seizures

MGI Mouse Phenotypes related to Wolf-Hirschhorn Syndrome:

43
# Description MGI Source Accession Score Top Affiliating Genes
1 craniofacial MP:0005382 9.35 FGFR3 LETM1 MSX1 NSD2 SALL4
2 digestive/alimentary MP:0005381 9.1 FGFR3 IQGAP1 MSX1 NSD2 SALL4 WFS1

Drugs & Therapeutics for Wolf-Hirschhorn Syndrome

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford Recruiting NCT01793168

Search NIH Clinical Center for Wolf-Hirschhorn Syndrome

Cochrane evidence based reviews: wolf-hirschhorn syndrome

Genetic Tests for Wolf-Hirschhorn Syndrome

Anatomical Context for Wolf-Hirschhorn Syndrome

MalaCards organs/tissues related to Wolf-Hirschhorn Syndrome:

38
Heart, Brain, Eye, Uterus, Bone, Spleen, Lung

Publications for Wolf-Hirschhorn Syndrome

Articles related to Wolf-Hirschhorn Syndrome:

(show top 50) (show all 247)
# Title Authors Year
1
Congenital cavitary optic disc anomaly and Axenfeld's anomaly in Wolf-Hirschhorn syndrome: A case report and review of the literature. ( 29199884 )
2018
2
Oligonephronia and Wolf-Hirschhorn syndrome: A further observation. ( 29193639 )
2018
3
Diabetes Mellitus Secondary to Acute Pancreatitis in a Child with Wolf-Hirschhorn Syndrome. ( 29204299 )
2017
4
A case for cannabidiol in Wolf-Hirschhorn syndrome seizure management. ( 28102593 )
2017
5
Wolf-Hirschhorn syndrome candidate 1-like 1 epigenetically regulates nephrin gene expression. ( 28228401 )
2017
6
Wolf-Hirschhorn Syndrome Candidate 1 Is Necessary for Correct Hematopoietic and B Cell Development. ( 28538178 )
2017
7
Wolf-Hirschhorn Syndrome Candidate 1 (whsc1) Functions as a Tumor Suppressor by Governing Cell Differentiation. ( 28654864 )
2017
8
Prenatal diagnosis of a 1.6-Mb 4p16.3 interstitial microdeletion encompassing FGFRL1 and TACC3 associated with bilateral cleft lip and palate of Wolf-Hirschhorn syndrome facial dysmorphism and short long bones. ( 29241927 )
2017
9
Neuroblastoma in a Child With Wolf-Hirschhorn Syndrome. ( 28085742 )
2017
10
Single port laparoscopic splenectomy for wandering spleen with splenomegaly in a patient with Wolf-Hirschhorn syndrome. ( 28281478 )
2017
11
Hepatoblastoma and Wolf-Hirschhorn syndrome: Coincidence or a new feature of a rare disease? ( 28786167 )
2017
12
Anesthetic considerations for a pediatric patient with Wolf-Hirschhorn syndrome: a case report. ( 29090255 )
2017
13
A structured assessment of motor function, behavior, and communication in patients with Wolf-Hirschhorn syndrome. ( 28818479 )
2017
14
Hepatic Malignancy in an Infant with Wolf-Hirschhorn Syndrome. ( 28266898 )
2017
15
Wolf-Hirschhorn Syndrome: Clinical and Genetic Data from a First Case Diagnosed in Central Africa. ( 28794913 )
2017
16
Treatment of intractable seizure in Wolf-Hirschhorn syndrome with bromide. ( 28377151 )
2017
17
Detection of recurrent 4p16.3 microdeletion with 2p25.3 microduplication by multiplex ligation-dependent probe amplification and array comparative genomic hybridization in a fetus from a family with Wolf-Hirschhorn syndrome. ( 26927259 )
2016
18
Early Postnatal Seizures in a Neonate with Wolf-Hirschhorn Syndrome. ( 27994945 )
2016
19
EP10.23: Application of 3D ultrasonography in analysis of fetal anomalies in Wolf-Hirschhorn syndrome. ( 27645370 )
2016
20
Successful treatment of migrating partial seizures in Wolf-Hirschhorn syndrome with bromide. ( 26797656 )
2016
21
Analyses of Genotypes and Phenotypes of Ten Chinese Patients with Wolf-Hirschhorn Syndrome by Multiplex Ligation-dependent Probe Amplification and Array Comparative Genomic Hybridization. ( 26960370 )
2016
22
Chromosomal microarray testing identifies a 4p terminal region associated with seizures in Wolf-Hirschhorn syndrome. ( 26747863 )
2016
23
Wolf-Hirschhorn Syndrome with Epibulbar Dermoid: An Unusual Association in a Patient with 4p Deletion and Functional Xp Disomy. ( 27842301 )
2016
24
Single port laparoscopic splenectomy for wandering spleen with splenomegaly in a patient with Wolf-Hirschhorn syndrome. ( 28000649 )
2016
25
Excellent response to levetiracetam in epilepsy with Wolf-Hirschhorn syndrome. ( 26590026 )
2016
26
Exploring the developmental mechanisms underlying Wolf-Hirschhorn Syndrome: Evidence for defects in neural crest cell migration. ( 27777068 )
2016
27
Airway Management in a Patient with Wolf-Hirschhorn Syndrome. ( 27752382 )
2016
28
Wolf-Hirschhorn syndrome: A review and update. ( 26239400 )
2015
29
Auditory hair cell defects as potential cause for sensorineural deafness in Wolf-Hirschhorn syndrome. ( 26092122 )
2015
30
Uncommon oral cleft in wolf-hirschhorn syndrome. ( 25831115 )
2015
31
Severe short stature and Wolf-Hirschhorn syndrome: response to growth hormone in two cases without growth hormone deficiency. ( 25988083 )
2015
32
Atypical Varicella in a Patient With Wolf-Hirschhorn Syndrome. ( 25673626 )
2015
33
Extensive Mongolian spots in 4p16.3 deletion (Wolf-Hirschhorn syndrome). ( 24859493 )
2014
34
Wolf-Hirschhorn syndrome: a case with normal karyotype, demonstrated by array CGH (aCGH). ( 25204484 )
2014
35
Wolf-Hirschhorn syndrome: a case study and disease overview. ( 25137600 )
2014
36
Unusual 4p16.3 deletions suggest an additional chromosome region for the Wolf-Hirschhorn syndrome-associated seizures disorder. ( 24738919 )
2014
37
Affinity for music in Wolf-Hirschhorn syndrome: two case reports. ( 25266617 )
2014
38
A cryptic unbalanced translocation der(4)t(4;17)(p16.1;q25.3) identifies Wittwer syndrome as a variant of Wolf-Hirschhorn syndrome. ( 25251057 )
2014
39
Clinical features in adult patient with Wolf-Hirschhorn syndrome. ( 24656633 )
2014
40
Phenotypic variations in wolf-hirschhorn syndrome. ( 25741211 )
2014
41
Wolf-Hirschhorn syndrome (WHS) - literature review on the features of the syndrome. ( 24979523 )
2014
42
Meiotic prophase I defects in an oligospermic man with Wolf-Hirschhorn syndrome with ring chromosome 4. ( 25057292 )
2014
43
A rare subtelomeric deletion syndrome: Wolf Hirschhorn syndrome. ( 25365852 )
2014
44
A case of 14q11.2 microdeletion with autistic features, severe obesity and facial dysmorphisms suggestive of Wolf-Hirschhorn syndrome. ( 24243641 )
2014
45
LETM1 haploinsufficiency causes mitochondrial defects in cells from humans with Wolf-Hirschhorn syndrome: implications for dissecting the underlying pathomechanisms in this condition. ( 24626991 )
2014
46
Microarray and FISH-based genotype-phenotype analysis of 22 Japanese patients with Wolf-Hirschhorn syndrome. ( 24357569 )
2013
47
Deletions involving genes WHSC1 and LETM1 may be necessary, but are not sufficient to cause Wolf-Hirschhorn syndrome. ( 23963300 )
2013
48
Letm1, the mitochondrial Ca2+/H+ antiporter, is essential for normal glucose metabolism and alters brain function in Wolf-Hirschhorn syndrome. ( 23716663 )
2013
49
Prenatal ultrasound findings observed in the Wolf-hirschhorn syndrome: Data from the registry of congenital malformations in auvergne. ( 24343879 )
2013
50
A case of wolf-hirschhorn syndrome and hypoplastic left heart syndrome. ( 22639003 )
2013

Variations for Wolf-Hirschhorn Syndrome

Copy number variations for Wolf-Hirschhorn Syndrome from CNVD:

7 (show all 14)
# CNVD ID Chromosom Start End Type Gene Symbol CNVD Disease
1 179944 4 1 3100000 Copy number Wolf-Hirschhorn syndrome
2 179946 4 1 3100000 Copy number LETM1 Wolf-Hirschhorn syndrome
3 179948 4 1 3100000 Copy number WHSC1 Wolf-Hirschhorn syndrome
4 179949 4 1 3100000 Copy number WHSC1 Wolf-Hirschhorn syndrome
5 179955 4 1 3100000 Microdeletion Wolf-Hirschhorn syndrome
6 179956 4 1 3100000 Microdeletion FGFR3 Wolf-Hirschhorn syndrome
7 179966 4 1 4500000 Deletion WHCR Wolf-Hirschhorn syndrome
8 185923 4 2567812 2704100 Microdeletion FAM193A Wolf-Hirschhorn syndrome
9 186013 4 2713184 2727859 Microdeletion TNIP2 Wolf-Hirschhorn syndrome
10 186039 4 2764547 2812621 Microdeletion SH3BP2 Wolf-Hirschhorn syndrome
11 186069 4 2815381 2901587 Microdeletion ADD1 Wolf-Hirschhorn syndrome
12 186114 4 2902092 2906359 Microdeletion MFSD10 Wolf-Hirschhorn syndrome
13 186117 4 2909461 2934916 Microdeletion NOP14 Wolf-Hirschhorn syndrome
14 186132 4 2935140 3012272 Microdeletion GRK4 Wolf-Hirschhorn syndrome

Expression for Wolf-Hirschhorn Syndrome

Search GEO for disease gene expression data for Wolf-Hirschhorn Syndrome.

Pathways for Wolf-Hirschhorn Syndrome

Pathways related to Wolf-Hirschhorn Syndrome according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.73 NSD2 NSD3
2 10.14 IQGAP1 TIAM1

GO Terms for Wolf-Hirschhorn Syndrome

Biological processes related to Wolf-Hirschhorn Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 embryonic limb morphogenesis GO:0030326 9.16 MSX1 SALL4
2 bone morphogenesis GO:0060349 8.96 FGFR3 MSX1
3 neuron projection extension GO:1990138 8.62 IQGAP1 TIAM1

Molecular functions related to Wolf-Hirschhorn Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 Rac GTPase binding GO:0048365 8.96 IQGAP1 TIAM1
2 histone-lysine N-methyltransferase activity GO:0018024 8.62 NSD2 NSD3

Sources for Wolf-Hirschhorn Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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