EVPLS
MCID: EVN003
MIFTS: 28

Even-Plus Syndrome (EVPLS)

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

Aliases & Classifications for Even-Plus Syndrome

MalaCards integrated aliases for Even-Plus Syndrome:

Name: Even-Plus Syndrome 56 58 73 36 6
Epiphyseal and Vertebral Dysplasia, Microtia, and Flat Nose, Plus Associated Malformations 56 73
Evpls 56 73
Epiphysial-Vertebral-Ear Dysplasia-Nose-Plus Associated Findings Syndrome 58

Characteristics:

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
based on report of 3 patients from 2 families (last curated march 2016)


HPO:

31
even-plus syndrome:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare bone diseases
Developmental anomalies during embryogenesis


Summaries for Even-Plus Syndrome

OMIM : 56 EVEN-PLUS syndrome is characterized by prenatal-onset short stature, vertebral and epiphyseal changes, microtia, midface hypoplasia with flat nose and triangular nares, cardiac malformations, and other findings including anal atresia, hypodontia, and aplasia cutis. The features overlap those reported in patients with CODAS syndrome (600373; Royer-Bertrand et al., 2015). (616854)

MalaCards based summary : Even-Plus Syndrome, also known as epiphyseal and vertebral dysplasia, microtia, and flat nose, plus associated malformations, is related to chronic interstitial cystitis and palmoplantar keratoderma, epidermolytic. An important gene associated with Even-Plus Syndrome is HSPA9 (Heat Shock Protein Family A (Hsp70) Member 9). Affiliated tissues include bone, kidney and thyroid, and related phenotypes are global developmental delay and microtia

KEGG : 36 EVEN-plus (epiphyseal, vertebral, ear, nose, plus associated findings) syndrome is a rare multiple congenital anomalies syndrome. Mutations in the HSPA9 gene, coding for the mitochondrial chaperone mortalin, cause EVEN-plus syndrome.

UniProtKB/Swiss-Prot : 73 Even-plus syndrome: An autosomal recessive syndrome characterized by epiphyseal and vertebral dysplasia, prenatal-onset short stature, a distinct craniofacial phenotype with microtia, a flat facial profile with flat nose and triangular nares, cardiac malformations, and additional findings such as anal atresia, hypodontia, aplasia cutis, and others.

Related Diseases for Even-Plus Syndrome

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

# Related Disease Score Top Affiliating Genes
1 chronic interstitial cystitis 10.3
2 palmoplantar keratoderma, epidermolytic 10.2
3 keratosis 10.2
4 palmoplantar keratosis 10.2
5 bullous pemphigoid 10.2
6 thyroid carcinoma 10.2
7 codas syndrome 9.9
8 microtia 9.9

Graphical network of the top 20 diseases related to Even-Plus Syndrome:



Diseases related to Even-Plus Syndrome

Symptoms & Phenotypes for Even-Plus Syndrome

Human phenotypes related to Even-Plus Syndrome:

31 (show all 28)
# Description HPO Frequency HPO Source Accession
1 global developmental delay 31 very rare (1%) HP:0001263
2 microtia 31 very rare (1%) HP:0008551
3 atrial septal defect 31 very rare (1%) HP:0001631
4 depressed nasal ridge 31 very rare (1%) HP:0000457
5 vesicoureteral reflux 31 very rare (1%) HP:0000076
6 synophrys 31 very rare (1%) HP:0000664
7 anal atresia 31 very rare (1%) HP:0002023
8 aplasia cutis congenita 31 very rare (1%) HP:0001057
9 bifid nasal tip 31 very rare (1%) HP:0000456
10 dysplastic corpus callosum 31 very rare (1%) HP:0006989
11 short neck 31 HP:0000470
12 agenesis of corpus callosum 31 HP:0001274
13 high palate 31 HP:0000218
14 short nose 31 HP:0003196
15 midface retrusion 31 HP:0011800
16 brachycephaly 31 HP:0000248
17 highly arched eyebrow 31 HP:0002553
18 epiphyseal dysplasia 31 HP:0002656
19 recurrent urinary tract infections 31 HP:0000010
20 oligohydramnios 31 HP:0001562
21 patent foramen ovale 31 HP:0001655
22 renal hypoplasia 31 HP:0000089
23 hypodontia 31 HP:0000668
24 sparse hair 31 HP:0008070
25 severe short stature 31 HP:0003510
26 atopic dermatitis 31 HP:0001047
27 coronal cleft vertebrae 31 HP:0003417
28 dysplasia of the femoral head 31 HP:0010575

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Neck:
short neck

Head And Neck Mouth:
high palate

Skeletal Skull:
brachycephaly

Head And Neck Eyes:
synophrys
arched eyebrows

Abdomen Gastrointestinal:
anal atresia

Skin Nails Hair Skin:
atopic dermatitis
aplasia cutis congenita on skull vertex

Head And Neck Nose:
hypoplastic nose
bifid tip of nose
triangular nares

Skeletal Spine:
coronal vertebral clefts
agenesis of the coccyx

Genitourinary Kidneys:
hypoplastic kidney

Head And Neck Ears:
severe microtia or anotia, with open ear ducts

Skeletal Pelvis:
dysplastic acetabula

Neurologic Central Nervous System:
agenesis of corpus callosum
developmental delay, mild to moderate
separated frontal horns

Head And Neck Head:
brachycephaly
aplasia cutis congenita on skull vertex

Genitourinary Ureters:
vesicoureteral reflux

Cardiovascular Heart:
patent foramen ovale
atrial septal defect, small
aneurysmal septum

Skin Nails Hair Hair:
sparse hair
lateral hair whorls

Head And Neck Face:
midface hypoplasia

Skeletal Limbs:
short long bones
dysplastic femoral heads
bifid distal femurs
epiphyseal dysplasia of distal femur
epiphyseal dysplasia of proximal tibia
more
Genitourinary Bladder:
urinary tract infection

Growth Height:
short stature, prenatal onset

Head And Neck Teeth:
single upper central incisor
absence of some lateral incisors

Clinical features from OMIM:

616854

Drugs & Therapeutics for Even-Plus Syndrome

Search Clinical Trials , NIH Clinical Center for Even-Plus Syndrome

Genetic Tests for Even-Plus Syndrome

Anatomical Context for Even-Plus Syndrome

MalaCards organs/tissues related to Even-Plus Syndrome:

40
Bone, Kidney, Thyroid

Publications for Even-Plus Syndrome

Articles related to Even-Plus Syndrome:

# Title Authors PMID Year
1
Mutations in the heat-shock protein A9 (HSPA9) gene cause the EVEN-PLUS syndrome of congenital malformations and skeletal dysplasia. 61 56 6
26598328 2015
2
Epiphyseal, vertebral, and ear (EVE) dysplasia: a new syndrome? 56
10424819 1999
3
Biophysical Consequences of EVEN-PLUS Syndrome Mutations for the Function of Mortalin. 61
30933555 2019
4
Spondyloepimetaphyseal dysplasia with neurodegeneration associated with AIFM1 mutation - a novel phenotype of the mitochondrial disease. 61
27102849 2017
5
Mitochondrial iron-sulfur cluster biogenesis from molecular understanding to clinical disease. 61
28064324 2017

Variations for Even-Plus Syndrome

ClinVar genetic disease variations for Even-Plus Syndrome:

6 ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 HSPA9 NM_004134.7(HSPA9):c.376C>T (p.Arg126Trp)SNV Pathogenic 224328 rs751478142 5:137906683-137906683 5:138570994-138570994
2 HSPA9 NM_004134.7(HSPA9):c.383A>G (p.Tyr128Cys)SNV Pathogenic 224329 rs765368797 5:137906676-137906676 5:138570987-138570987
3 HSPA9 NM_004134.7(HSPA9):c.882_883del (p.Gly295_Val296insTer)deletion Pathogenic 224330 rs772570880 5:137902404-137902405 5:138566715-138566716

UniProtKB/Swiss-Prot genetic disease variations for Even-Plus Syndrome:

73
# Symbol AA change Variation ID SNP ID
1 HSPA9 p.Arg126Trp VAR_076662 rs751478142
2 HSPA9 p.Tyr128Cys VAR_076663 rs765368797

Expression for Even-Plus Syndrome

Search GEO for disease gene expression data for Even-Plus Syndrome.

Pathways for Even-Plus Syndrome

GO Terms for Even-Plus Syndrome

Sources for Even-Plus Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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