YVS
MCID: YNS002
MIFTS: 47

Yunis-Varon Syndrome (YVS)

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

Aliases & Classifications for Yunis-Varon Syndrome

MalaCards integrated aliases for Yunis-Varon Syndrome:

Name: Yunis-Varon Syndrome 58 12 77 54 60 76 38 15
Yunis Varon Syndrome 54 30 6 45 41 74
Cleidocranial Dysplasia with Micrognathia, Absent Thumbs, and Distal Aphalangia 58 12 76
Cleidocranial Dysplasia-Micrognathia-Absent Thumbs Syndrome 12 60
Yvs 58 76
Cleidocranial Dysplasia, Micrognathia, Absent Thumbs, & Distal Aphalangia 54
Yunis-Varón Syndrome 54

Characteristics:

Orphanet epidemiological data:

60
yunis-varon syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide);

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
death in infancy in majority of patients


HPO:

33
yunis-varon syndrome:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Yunis-Varon Syndrome

NIH Rare Diseases : 54 Yunis-Varon syndrome is a rare condition that affects many different parts of the body. Signs and symptoms are generally present from birth and may include underdeveloped or absent collarbones (clavicles); large fontanelles; characteristic facial features; hypotonia (reduced muscle tone) and/or abnormalities of the fingers and toes. Affected people may also experience feeding difficulties, breathing problems, brain malformations, heart defects, skeletal abnormalities, developmental delay, and/or intellectual disability. Yunis-Varon syndrome is caused by changes (mutations) in the FIG4 gene and is inherited in an autosomal recessive manner. Treatment is based on the signs and symptoms present in each person.

MalaCards based summary : Yunis-Varon Syndrome, also known as yunis varon syndrome, is related to pulmonary hypertension and lysosomal storage disease. An important gene associated with Yunis-Varon Syndrome is FIG4 (FIG4 Phosphoinositide 5-Phosphatase), and among its related pathways/superpathways are Glycerophospholipid biosynthesis and MHC class II antigen presentation. Affiliated tissues include brain, skin and eye, and related phenotypes are aplasia of the distal phalanges of the hand and aplasia of the distal phalanx of the hallux

Disease Ontology : 12 A syndrome characterized by skeletal defects, including cleidocranial dysplasia and digital anomalies, and severe neurologic involvement with neuronal loss. Enlarged cytoplasmic vacuoles are found in neurons, muscle, and cartilage. It is usually lethal in infancy and has material basis in homozygous or compound heterozygous mutation in the FIG4 gene on chromosome 6q21.

OMIM : 58 Yunis-Varon syndrome is a severe autosomal recessive disorder characterized by skeletal defects, including cleidocranial dysplasia and digital anomalies, and severe neurologic involvement with neuronal loss. Enlarged cytoplasmic vacuoles are found in neurons, muscle, and cartilage. The disorder is usually lethal in infancy (summary by Campeau et al., 2013). (216340)

UniProtKB/Swiss-Prot : 76 Yunis-Varon syndrome: A severe autosomal recessive disorder characterized by skeletal defects, including cleidocranial dysplasia and digital anomalies, and severe neurologic involvement with neuronal loss. Enlarged cytoplasmic vacuoles are found in neurons, muscle, and cartilage. The disorder is usually lethal in infancy.

Wikipedia : 77 Yunis–Varon syndrome (YVS), also called cleidocranial dysplasia with micrognathia, absent thumbs and... more...

Related Diseases for Yunis-Varon Syndrome

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

# Related Disease Score Top Affiliating Genes
1 pulmonary hypertension 10.5
2 lysosomal storage disease 10.4
3 cleft lip 10.4
4 cleft lip/palate 10.4
5 congenital anomalies of kidney and urinary tract 2 10.1
6 burns 10.1
7 bladder neck obstruction 10.1
8 charcot-marie-tooth disease, type 4j 9.6 FIG4 PIKFYVE VAC14

Graphical network of the top 20 diseases related to Yunis-Varon Syndrome:



Diseases related to Yunis-Varon Syndrome

Symptoms & Phenotypes for Yunis-Varon Syndrome

Human phenotypes related to Yunis-Varon Syndrome:

60 33 (show top 50) (show all 111)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 aplasia of the distal phalanges of the hand 60 33 hallmark (90%) Very frequent (99-80%) HP:0009881
2 aplasia of the distal phalanx of the hallux 60 33 hallmark (90%) Very frequent (99-80%) HP:0010102
3 short proximal phalanx of hallux 60 33 hallmark (90%) Very frequent (99-80%) HP:0010107
4 hypertelorism 60 33 frequent (33%) Frequent (79-30%) HP:0000316
5 low-set ears 60 33 frequent (33%) Frequent (79-30%) HP:0000369
6 agenesis of corpus callosum 60 33 frequent (33%) Frequent (79-30%) HP:0001274
7 cataract 60 33 frequent (33%) Frequent (79-30%) HP:0000518
8 global developmental delay 60 33 frequent (33%) Frequent (79-30%) HP:0001263
9 anteverted nares 60 33 frequent (33%) Frequent (79-30%) HP:0000463
10 short stature 60 33 frequent (33%) Frequent (79-30%) HP:0004322
11 cardiomegaly 60 33 frequent (33%) Frequent (79-30%) HP:0001640
12 micrognathia 60 33 frequent (33%) Frequent (79-30%) HP:0000347
13 pulmonary arterial hypertension 60 33 frequent (33%) Frequent (79-30%) HP:0002092
14 dolichocephaly 60 33 frequent (33%) Frequent (79-30%) HP:0000268
15 metatarsus adductus 60 33 frequent (33%) Frequent (79-30%) HP:0001840
16 aplasia/hypoplasia of the nipples 60 33 frequent (33%) Frequent (79-30%) HP:0006709
17 postnatal growth retardation 60 33 frequent (33%) Frequent (79-30%) HP:0008897
18 high, narrow palate 60 33 frequent (33%) Frequent (79-30%) HP:0002705
19 cardiomyopathy 60 33 frequent (33%) Frequent (79-30%) HP:0001638
20 short philtrum 60 33 frequent (33%) Frequent (79-30%) HP:0000322
21 hypospadias 60 33 frequent (33%) Frequent (79-30%) HP:0000047
22 hypoplasia of the frontal lobes 60 33 frequent (33%) Frequent (79-30%) HP:0007333
23 upslanted palpebral fissure 60 33 frequent (33%) Frequent (79-30%) HP:0000582
24 ventricular septal defect 60 33 frequent (33%) Frequent (79-30%) HP:0001629
25 arrhinencephaly 60 33 frequent (33%) Frequent (79-30%) HP:0002139
26 sparse scalp hair 60 33 frequent (33%) Frequent (79-30%) HP:0002209
27 high forehead 60 33 frequent (33%) Frequent (79-30%) HP:0000348
28 proptosis 60 33 frequent (33%) Frequent (79-30%) HP:0000520
29 severe failure to thrive 60 33 frequent (33%) Frequent (79-30%) HP:0001525
30 thin vermilion border 60 33 frequent (33%) Frequent (79-30%) HP:0000233
31 sclerocornea 60 33 frequent (33%) Frequent (79-30%) HP:0000647
32 pachygyria 60 33 frequent (33%) Frequent (79-30%) HP:0001302
33 tapered finger 60 33 frequent (33%) Frequent (79-30%) HP:0001182
34 micropenis 60 33 frequent (33%) Frequent (79-30%) HP:0000054
35 single transverse palmar crease 60 33 frequent (33%) Frequent (79-30%) HP:0000954
36 decreased skull ossification 60 33 frequent (33%) Frequent (79-30%) HP:0004331
37 rocker bottom foot 60 33 frequent (33%) Frequent (79-30%) HP:0001838
38 sparse eyebrow 60 33 frequent (33%) Frequent (79-30%) HP:0045075
39 sparse eyelashes 60 33 frequent (33%) Frequent (79-30%) HP:0000653
40 generalized neonatal hypotonia 60 33 frequent (33%) Frequent (79-30%) HP:0008935
41 neuronal loss in central nervous system 60 33 frequent (33%) Frequent (79-30%) HP:0002529
42 short chin 60 33 frequent (33%) Frequent (79-30%) HP:0000331
43 syndactyly 60 33 frequent (33%) Frequent (79-30%) HP:0001159
44 aplasia/hypoplasia of the clavicles 60 33 frequent (33%) Frequent (79-30%) HP:0006710
45 short upper lip 60 33 frequent (33%) Frequent (79-30%) HP:0000188
46 short middle phalanx of finger 60 33 frequent (33%) Frequent (79-30%) HP:0005819
47 aplasia of the 1st metacarpal 60 33 frequent (33%) Frequent (79-30%) HP:0010035
48 redundant neck skin 60 33 frequent (33%) Frequent (79-30%) HP:0005989
49 premature loss of primary teeth 60 33 frequent (33%) Frequent (79-30%) HP:0006323
50 bilateral microphthalmos 60 33 frequent (33%) Frequent (79-30%) HP:0007633

Symptoms via clinical synopsis from OMIM:

58
Head And Neck Eyes:
hypertelorism
sclerocornea
cataracts
upslanting palpebral fissures
protruding eyes
more
Neurologic Central Nervous System:
agenesis of corpus callosum
pachygyria
hypotonia
frontal lobe atrophy
severe developmental delay in survivors
more
Head And Neck Nose:
anteverted nares

Genitourinary Internal Genitalia Male:
cryptorchidism

Cardiovascular Heart:
cardiomyopathy
tetralogy of fallot
ventricular septal defect
congenital heart defect

Genitourinary External Genitalia Male:
hypospadias
micropenis

Skin Nails Hair Hair:
sparse scalp hair
sparse eyebrows and eyelashes

Skeletal Skull:
decreased skull ossification
hypoplastic facial bones
widened sutures

Skeletal Feet:
syndactyly
aplastic/hypoplastic distal phalanges
aplastic/hypoplastic halluces
short, tapering toes
aplastic/hypoplastic first metatarsal

Chest Ribs Sternum Clavicles And Scapulae:
absent sternal ossification
hypoplastic clavicles
absent clavicles
abnormal scapula

Growth Other:
prenatal growth retardation
severe postnatal failure to thrive

Cardiovascular Vascular:
primary pulmonary hypertension

Head And Neck Neck:
loose nuchal skin

Hematology:
vacuolated macrophages

Laboratory Abnormalities:
enlarged cytoplasmic vacuoles in bone, muscle, and brain tissue

Head And Neck Ears:
low-set ears
hearing loss
dysplastic ears
hypoplastic ear lobes

Head And Neck Head:
microcephaly
dolichocephaly
enlarged fontanels

Head And Neck Face:
micrognathia
short philtrum

Prenatal Manifestations:
hydrops fetalis

Skeletal Pelvis:
hip dislocation
flattened acetabula
iliac hypoplasia

Prenatal Manifestations Amniotic Fluid:
polyhydramnios

Abdomen Gastrointestinal:
pyloric stenosis
weak sucking

Skeletal Hands:
syndactyly
transverse palmar creases
aplastic/hypoplastic thumbs
short, tapering fingers
aplastic/hypoplastic middle phalanges
more
Head And Neck Mouth:
short upper lip
broad secondary alveolar ridge
thin lips
labiogingival retraction
narrow-arched palate

Chest Breasts:
absent nipples

Skin Nails Hair Skin:
transverse palmar creases

Head And Neck Teeth:
premature loss of deciduous teeth
cystic dental follicles

Skin Nails Hair Nails:
nail aplasia/hypoplasia

Prenatal Manifestations Delivery:
preterm delivery

Clinical features from OMIM:

216340

MGI Mouse Phenotypes related to Yunis-Varon Syndrome:

47
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.43 DNM1 ENO2 FIG4 MCOLN1 PIKFYVE VAC14
2 nervous system MP:0003631 9.1 DNM1 ENO2 FIG4 MCOLN1 PIKFYVE VAC14

Drugs & Therapeutics for Yunis-Varon Syndrome

Search Clinical Trials , NIH Clinical Center for Yunis-Varon Syndrome

Cochrane evidence based reviews: yunis varon syndrome

Genetic Tests for Yunis-Varon Syndrome

Genetic tests related to Yunis-Varon Syndrome:

# Genetic test Affiliating Genes
1 Yunis Varon Syndrome 30 FIG4

Anatomical Context for Yunis-Varon Syndrome

MalaCards organs/tissues related to Yunis-Varon Syndrome:

42
Brain, Skin, Eye

Publications for Yunis-Varon Syndrome

Articles related to Yunis-Varon Syndrome:

(show all 20)
# Title Authors Year
1
Yunis-Varon Syndrome. ( 31094135 )
2019
2
Yunis-Varón syndrome caused by biallelic VAC14 mutations. ( 28635952 )
2017
3
Yunis-varon syndrome: further delineation of cardiovascular and endocrine outcome. ( 24610892 )
2014
4
Yunis-Varón syndrome: the first report of two Iranian cases. ( 24658994 )
2014
5
Yunis-Varón syndrome is caused by mutations in FIG4, encoding a phosphoinositide phosphatase. ( 23623387 )
2013
6
Novel FIG4 mutations in Yunis-Varon syndrome. ( 24088667 )
2013
7
Primary pulmonary hypertension, congenital heart defect, central nervous system malformations, hypo- and aplastic toes: another case of Yunis-Varón syndrome or report of a new entity. ( 22044576 )
2012
8
New ocular findings in two sisters with Yunis-Varón syndrome and literature review. ( 20932945 )
2011
9
Yunis-Varon syndrome: further delineation of the phenotype. ( 18203163 )
2008
10
Yunis Varon syndrome. ( 16816498 )
2006
11
Yunis-Varon syndrome. ( 15876600 )
2005
12
A case of Yunis-Varon syndrome complicated with complete cleft lip and palate. ( 14755473 )
2004
13
Yunis-Varon syndrome: evidence for a lysosomal storage disease. ( 11078567 )
2000
14
Atrophy of the left lobe of the liver and anomalous hepatic vessel in a patient with Yunis-Varon syndrome. ( 10478891 )
1999
15
Yunis-Varon syndrome: the first case of German origin. ( 8818450 )
1996
16
Generalized lysosomal storage in Yunis Varón syndrome. ( 7496176 )
1995
17
Congenital heart malformation in Yunis-Varón syndrome. ( 8411078 )
1993
18
Hypodontia, impacted permanent teeth, spinal defects, and cardiomegaly in a previously diagnosed case of the Yunis-Varon syndrome. ( 1533447 )
1992
19
Yunis-Varon syndrome with severe osteodysplasty. ( 2319578 )
1990
20
Further delineation of the Yunis-Varon syndrome. ( 2918527 )
1989

Variations for Yunis-Varon Syndrome

UniProtKB/Swiss-Prot genetic disease variations for Yunis-Varon Syndrome:

76
# Symbol AA change Variation ID SNP ID
1 FIG4 p.Gly104Asp VAR_070051 rs397509395
2 FIG4 p.Leu175Pro VAR_070052 rs397514707

ClinVar genetic disease variations for Yunis-Varon Syndrome:

6 (show all 16)
# Gene Variation Type Significance SNP ID Assembly Location
1 FIG4 NM_014845.5(FIG4): c.1260_1261delGT (p.Thr422Glnfs) deletion Pathogenic rs397509394 GRCh37 Chromosome 6, 110081575: 110081576
2 FIG4 NM_014845.5(FIG4): c.1260_1261delGT (p.Thr422Glnfs) deletion Pathogenic rs397509394 GRCh38 Chromosome 6, 109760372: 109760373
3 FIG4 NM_014845.5(FIG4): c.311G> A (p.Gly104Asp) single nucleotide variant Pathogenic rs397509395 GRCh37 Chromosome 6, 110048333: 110048333
4 FIG4 NM_014845.5(FIG4): c.311G> A (p.Gly104Asp) single nucleotide variant Pathogenic rs397509395 GRCh38 Chromosome 6, 109727130: 109727130
5 FIG4 NM_014845.5(FIG4): c.831_838delTAAATTTG (p.Lys278Trpfs) deletion Pathogenic rs786200937 GRCh37 Chromosome 6, 110062702: 110062709
6 FIG4 NM_014845.5(FIG4): c.831_838delTAAATTTG (p.Lys278Trpfs) deletion Pathogenic rs786200937 GRCh38 Chromosome 6, 109741499: 109741506
7 FIG4 NM_014845.5(FIG4): c.524T> C (p.Leu175Pro) single nucleotide variant Pathogenic rs397514707 GRCh37 Chromosome 6, 110056379: 110056379
8 FIG4 NM_014845.5(FIG4): c.524T> C (p.Leu175Pro) single nucleotide variant Pathogenic rs397514707 GRCh38 Chromosome 6, 109735176: 109735176
9 VAC14 NM_018052.3(VAC14): c.1895C> T (p.Thr632Met) single nucleotide variant Uncertain significance rs1060499667 GRCh38 Chromosome 16, 70697199: 70697199
10 VAC14 NM_018052.3(VAC14): c.1895C> T (p.Thr632Met) single nucleotide variant Uncertain significance rs1060499667 GRCh37 Chromosome 16, 70731102: 70731102
11 VAC14 NM_018052.3(VAC14): c.923T> A (p.Leu308Ter) single nucleotide variant Uncertain significance rs769608639 GRCh38 Chromosome 16, 70781892: 70781892
12 VAC14 NM_018052.3(VAC14): c.923T> A (p.Leu308Ter) single nucleotide variant Uncertain significance rs769608639 GRCh37 Chromosome 16, 70815795: 70815795
13 FIG4 NM_014845.5(FIG4): c.834A> T (p.Lys278Asn) single nucleotide variant Uncertain significance rs138048706 GRCh37 Chromosome 6, 110062705: 110062705
14 FIG4 NM_014845.5(FIG4): c.834A> T (p.Lys278Asn) single nucleotide variant Uncertain significance rs138048706 GRCh38 Chromosome 6, 109741502: 109741502
15 FIG4 NM_014845.5(FIG4): c.737G> A (p.Trp246Ter) single nucleotide variant Pathogenic/Likely pathogenic rs776005417 GRCh38 Chromosome 6, 109738415: 109738415
16 FIG4 NM_014845.5(FIG4): c.737G> A (p.Trp246Ter) single nucleotide variant Pathogenic/Likely pathogenic rs776005417 GRCh37 Chromosome 6, 110059618: 110059618

Expression for Yunis-Varon Syndrome

Search GEO for disease gene expression data for Yunis-Varon Syndrome.

Pathways for Yunis-Varon Syndrome

GO Terms for Yunis-Varon Syndrome

Cellular components related to Yunis-Varon Syndrome according to GeneCards Suite gene sharing:

(show all 14)
# Name GO ID Score Top Affiliating Genes
1 Golgi apparatus GO:0005794 9.84 DNM1 FIG4 RAB7A RAB7B
2 lysosome GO:0005764 9.67 MCOLN1 RAB7A RAB7B
3 cytoplasmic vesicle GO:0031410 9.65 DNM1 MCOLN1 PIKFYVE RAB7A RAB7B
4 endosome GO:0005768 9.63 FIG4 MCOLN1 PIKFYVE RAB7A RAB7B VAC14
5 early endosome membrane GO:0031901 9.58 FIG4 PIKFYVE VAC14
6 late endosome GO:0005770 9.54 MCOLN1 RAB7A RAB7B
7 lipid droplet GO:0005811 9.52 FIG4 RAB7A
8 phagocytic vesicle GO:0045335 9.51 RAB7A RAB7B
9 phagocytic vesicle membrane GO:0030670 9.5 MCOLN1 RAB7A RAB7B
10 photoreceptor inner segment GO:0001917 9.48 DNM1 ENO2
11 vacuolar membrane GO:0005774 9.43 RAB7A RAB7B
12 endosome membrane GO:0010008 9.35 FIG4 MCOLN1 PIKFYVE RAB7A VAC14
13 late endosome membrane GO:0031902 9.1 FIG4 MCOLN1 PIKFYVE RAB7A RAB7B VAC14
14 membrane GO:0016020 10.06 DNM1 ENO2 FIG4 MCOLN1 PIKFYVE RAB7A

Biological processes related to Yunis-Varon Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 retrograde transport, endosome to Golgi GO:0042147 9.43 PIKFYVE RAB7A
2 Rab protein signal transduction GO:0032482 9.4 RAB7A RAB7B
3 phosphatidylinositol-3-phosphate biosynthetic process GO:0036092 9.37 FIG4 PIKFYVE
4 endosome to lysosome transport GO:0008333 9.32 RAB7A RAB7B
5 phosphatidylinositol metabolic process GO:0046488 9.26 FIG4 PIKFYVE
6 myelin assembly GO:0032288 9.16 FIG4 PIKFYVE
7 phagosome-lysosome fusion GO:0090385 8.96 RAB7A RAB7B
8 phosphatidylinositol biosynthetic process GO:0006661 8.8 FIG4 PIKFYVE VAC14

Molecular functions related to Yunis-Varon Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 GTP binding GO:0005525 9.33 DNM1 RAB7A RAB7B
2 GTPase activity GO:0003924 9.13 DNM1 RAB7A RAB7B
3 phosphatidylinositol-3,5-bisphosphate 5-phosphatase activity GO:0043813 8.62 FIG4 PIKFYVE

Sources for Yunis-Varon Syndrome

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