Codas Syndrome (CODASS)

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

Aliases & Classifications for Codas Syndrome

MalaCards integrated aliases for Codas Syndrome:

Name: Codas Syndrome 56 12 52 58 73 36 29 6 43 71
Cerebral, Ocular, Dental, Auricular, and Skeletal Anomalies Syndrome 56 73
Cerebral, Ocular, Dental, Auricular, and Skeletal Syndrome 12 52
Cerebro-Oculo-Dento-Auriculo-Skeletal Syndrome 12 52
Syndrome, Cerebral, Ocular, Dental, Auricular, Skeletal 39
Cerebrooculodentoauriculoskeletal Syndrome 58
Codass 73


Orphanet epidemiological data:

codas syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;


autosomal recessive

codas is an acronym for cerebral ocular dental auricular skeletal syndrome


codas syndrome:
Inheritance autosomal recessive inheritance


Orphanet: 58  
Rare eye diseases
Rare bone diseases
Developmental anomalies during embryogenesis

Summaries for Codas Syndrome

NIH Rare Diseases : 52 The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 1458 Definition Codas syndrome is a multiple congenital anomalies syndrome characterized by Cerebral, Ocular, Dental, Auricular and Skeletal anomalies. Epidemiology To date, three affected children (an unrelated Canadian girl and boy of Mennonite descent, and a girl from Brazil) have been reported. Clinical description Characteristic features consist of psychomotor delay, cataracts , abnormally shaped teeth (including enamel projections extending from the tips of the cusps), delayed tooth eruption, malformed ears (overfolded and crumpled ears), sensorineural hearing loss , short stature with marked epiphyseal dysplasia, and an unusual facial phenotype characterized mainly by ptosis , epicanthal folds and a grooved nose. Etiology Etiology remains unknown but some of the features suggest involvement of a collagen gene defect. Diagnostic methods X-rays show delayed ossification, delayed bone age and spine and pelvic anomalies. Differential diagnosis The differential diagnosis should include chondrodysplasia punctata (the rhizomelic, Conradi-Hunermann, and X-linked dominant types) and Kabuki syndrome (see these terms). Genetic counseling The occurrence of two affected children within the Manitoba Mennonite community (a genetic isolate) suggests autosomal recessive inheritance, but other modes of transmission could not be excluded. Familial recurrence has not been documented. Management and treatment Management requires a multidisciplinary approach by specialists in neurology, ophthalmology, otorhinolaryngology, odontology, orthopedics and genetics. Visit the Orphanet disease page for more resources.

MalaCards based summary : Codas Syndrome, also known as cerebral, ocular, dental, auricular, and skeletal anomalies syndrome, is related to even-plus syndrome and cataract. An important gene associated with Codas Syndrome is LONP1 (Lon Peptidase 1, Mitochondrial). Affiliated tissues include bone, eye and tongue, and related phenotypes are abnormality of epiphysis morphology and cataract

Disease Ontology : 12 A syndrome characterized by developmental delay, and cerebral, ocular, dental, auricular, and skeletal anomalies that has material basis in homozygous or compound heterozygous mutation in LONP1 on 19p13.3.

OMIM : 56 CODAS is an acronym for cerebral, ocular, dental, auricular, and skeletal anomalies. CODAS syndrome is a rare disorder characterized by a distinctive constellation of features that includes developmental delay, craniofacial anomalies, cataracts, ptosis, median nasal groove, delayed tooth eruption, hearing loss, short stature, delayed epiphyseal ossification, metaphyseal hip dysplasia, and vertebral coronal clefts (summary by Strauss et al., 2015). (600373)

KEGG : 36 CODAS (cerebral, ocular, dental, auricular, skeletal anomalies) syndrome is a rare multiple congenital anomalies syndrome. The anomalies referred to in the acronym are as follows: cerebral-developmental delay, ocular-cataracts, dental-aberrant cusp morphology and delayed eruption, auricular-malformations of the external ear, and skeletal-spondyloepiphyseal dysplasia. The disorder is highly distinctive with characteristic features consisting of developmental delay, cataracts, unusual enamel projections, overfolded and crumpled ears, epiphyseal dysplasia, and dysmorphic features (grooved nose, ptosis). Recently, mutations in LONP1 gene have been mapped and identified as causative of this disorder. LONP1 encodes Lon protease, a homohexameric enzyme that mediates protein quality control, respiratory-complex assembly, gene expression, and stress responses in mitochondria.

UniProtKB/Swiss-Prot : 73 CODAS syndrome: A rare syndrome characterized by the combination of cerebral, ocular, dental, auricular, and skeletal features. These include developmental delay, craniofacial anomalies, cataracts, ptosis, median nasal groove, delayed tooth eruption, hearing loss, short stature, delayed epiphyseal ossification, metaphyseal hip dysplasia, and vertebral coronal clefts.

Related Diseases for Codas Syndrome

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

Diseases related to Codas Syndrome

Symptoms & Phenotypes for Codas Syndrome

Human phenotypes related to Codas Syndrome:

58 31 (show top 50) (show all 64)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 abnormality of epiphysis morphology 58 31 hallmark (90%) Very frequent (99-80%) HP:0005930
2 cataract 58 31 very rare (1%) Very frequent (99-80%) HP:0000518
3 global developmental delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0001263
4 delayed skeletal maturation 58 31 hallmark (90%) Very frequent (99-80%) HP:0002750
5 depressed nasal bridge 58 31 hallmark (90%) Very frequent (99-80%) HP:0005280
6 short nose 58 31 hallmark (90%) Very frequent (99-80%) HP:0003196
7 brachydactyly 58 31 hallmark (90%) Very frequent (99-80%) HP:0001156
8 short stature 58 31 very rare (1%) Very frequent (99-80%) HP:0004322
9 short metacarpal 58 31 hallmark (90%) Very frequent (99-80%) HP:0010049
10 anteverted nares 58 31 very rare (1%) Very frequent (99-80%) HP:0000463
11 delayed eruption of teeth 58 31 very rare (1%) Very frequent (99-80%) HP:0000684
12 epicanthus 58 31 hallmark (90%) Very frequent (99-80%) HP:0000286
13 flat face 58 31 hallmark (90%) Very frequent (99-80%) HP:0012368
14 overfolded helix 58 31 hallmark (90%) Very frequent (99-80%) HP:0000396
15 abnormality of dental enamel 58 31 hallmark (90%) Very frequent (99-80%) HP:0000682
16 abnormality of dental morphology 58 31 hallmark (90%) Very frequent (99-80%) HP:0006482
17 crumpled ear 58 31 very rare (1%) Very frequent (99-80%) HP:0009901
18 coronal cleft vertebrae 58 31 very rare (1%) Very frequent (99-80%) HP:0003417
19 midline defect of the nose 58 31 hallmark (90%) Very frequent (99-80%) HP:0004122
20 scoliosis 58 31 very rare (1%) Frequent (79-30%) HP:0002650
21 ptosis 58 31 very rare (1%) Frequent (79-30%) HP:0000508
22 muscular hypotonia 58 31 frequent (33%) Frequent (79-30%) HP:0001252
23 sensorineural hearing impairment 58 31 very rare (1%) Frequent (79-30%) HP:0000407
24 joint hyperflexibility 58 31 frequent (33%) Frequent (79-30%) HP:0005692
25 congenital hip dislocation 58 31 frequent (33%) Frequent (79-30%) HP:0001374
26 nystagmus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000639
27 ventricular septal defect 58 31 occasional (7.5%) Occasional (29-5%) HP:0001629
28 strabismus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000486
29 hydroureter 58 31 occasional (7.5%) Occasional (29-5%) HP:0000072
30 abnormality of the larynx 58 31 occasional (7.5%) Occasional (29-5%) HP:0001600
31 extrahepatic biliary duct atresia 58 31 occasional (7.5%) Occasional (29-5%) HP:0005242
32 proximal placement of thumb 31 occasional (7.5%) HP:0009623
33 genu valgum 31 very rare (1%) HP:0002857
34 intellectual disability 31 very rare (1%) HP:0001249
35 seizures 31 very rare (1%) HP:0001250
36 cryptorchidism 31 very rare (1%) HP:0000028
37 gastroesophageal reflux 31 very rare (1%) HP:0002020
38 generalized hypotonia 31 very rare (1%) HP:0001290
39 atrial septal defect 31 very rare (1%) HP:0001631
40 motor delay 31 very rare (1%) HP:0001270
41 conductive hearing impairment 31 very rare (1%) HP:0000405
42 anal atresia 31 very rare (1%) HP:0002023
43 rectovaginal fistula 31 very rare (1%) HP:0000143
44 omphalocele 31 very rare (1%) HP:0001539
45 hypoplasia of the odontoid process 31 very rare (1%) HP:0003311
46 vocal cord paresis 31 very rare (1%) HP:0001604
47 pes valgus 31 very rare (1%) HP:0008081
48 metaphyseal dysplasia 31 very rare (1%) HP:0100255
49 hypoplasia of dental enamel 31 very rare (1%) HP:0006297
50 polyhydramnios 31 HP:0001561

Symptoms via clinical synopsis from OMIM:

Skeletal Limbs:
genu valgum
metaphyseal dysplasia
short humeri
delayed ossification of epiphyses
hypoplastic or absent epiphyses
Growth Height:
short stature

Cardiovascular Heart:
ventricular septal defect
atrial septal defect
atrioventricular canal defect

Prenatal Manifestations Amniotic Fluid:

Head And Neck Head:
broad skull

Skeletal Feet:
pes valgus

Head And Neck Teeth:
delayed tooth eruption
enamel dysplasia
abnormal cusp morphology

delayed bone age
hypermobility of all joints

Abdomen Gastrointestinal:
imperforate anus (in some patients)
rectovaginal fistula (rare)

Skeletal Spine:
odontoid hypoplasia
vertebral coronal clefts (t11-s2)
thoracic and lumbar scoliosis

Head And Neck Face:
flattened midface

Abdomen Biliary Tract:
extrahepatic bile duct atresia (rare)

Prenatal Manifestations Placenta And Umbilical Cord:
two-vessel umbilical cord

Head And Neck Eyes:
cataract, postnatal, bilateral dense nuclear

Growth Weight:
short stature
length less than 5th percentile

Head And Neck Nose:
anteverted nares
flat nasal bridge
grooved nasal tip

Skeletal Pelvis:
congenital hip dislocation
square iliac bones
flat, irregular acetabular margins

Respiratory Larynx:
vocal cord paresis
glottic narrowing
vocal cord atrophy

Neurologic Central Nervous System:
developmental delay
seizures (rare)
thin corpus callosum
prominent cortical sulci
Skeletal Hands:
short metacarpals
short phalanges
delayed carpal ossification
proximally placed thumbs (rare)

Head And Neck Ears:
sensorineural hearing loss
overfolded, rumpled ears
impaired tympanic membrane mobility
low-frequency conductive hearing loss

Genitourinary Internal Genitalia Male:
cryptorchidism (in some patients)

Abdomen External Features:
omphalocele (in some patients)

Head And Neck Mouth:
chronic sialorrhea
hemiatrophy of tongue (in some patients)

Genitourinary Ureters:
dilated ureter (rare)

Clinical features from OMIM:


Drugs & Therapeutics for Codas Syndrome

Search Clinical Trials , NIH Clinical Center for Codas Syndrome

Cochrane evidence based reviews: codas syndrome

Genetic Tests for Codas Syndrome

Genetic tests related to Codas Syndrome:

# Genetic test Affiliating Genes
1 Codas Syndrome 29 LONP1

Anatomical Context for Codas Syndrome

MalaCards organs/tissues related to Codas Syndrome:

Bone, Eye, Tongue

Publications for Codas Syndrome

Articles related to Codas Syndrome:

(show all 17)
# Title Authors PMID Year
CODAS syndrome is associated with mutations of LONP1, encoding mitochondrial AAA+ Lon protease. 61 56 6
25574826 2015
Newly recognized syndrome of cerebral, ocular, dental, auricular, skeletal anomalies: CODAS syndrome--a case report. 61 56 6
1887855 1991
Fourth case of cerebral, ocular, dental, auricular, skeletal syndrome (CODAS), description of new features and molecular analysis. 61 56
20503327 2010
Third case of cerebral, ocular, dental, auricular, skeletal anomalies (CODAS) syndrome, further delineating a new malformation syndrome: first report of an affected male and review of literature. 61 56
11471171 2001
CODAS syndrome: a new distinct MCA/MR syndrome with radiological changes of spondyloepiphyseal dysplasia. Another case report. 61 56
7702089 1995
Mutations in the heat-shock protein A9 (HSPA9) gene cause the EVEN-PLUS syndrome of congenital malformations and skeletal dysplasia. 56
26598328 2015
Global Proteome of LonP1+/- Mouse Embryonal Fibroblasts Reveals Impact on Respiratory Chain, but No Interdependence between Eral1 and Mitoribosomes. 61
31547314 2019
Five-year follow-up outcomes of comprehensive rehabilitation in Korean siblings with cerebral, ocular, dental, auricular, skeletal anomalies (CODAS) syndrome: A case report. 61
31169704 2019
Expanding the Clinical Spectrum of LONP1-Related Mitochondrial Cytopathy. 61
31636596 2019
Clinical features of LONP1-related infantile cataract. 61
29408517 2018
Defective mitochondrial protease LonP1 can cause classical mitochondrial disease. 61
29518248 2018
A novel mutation in the proteolytic domain of LONP1 causes atypical CODAS syndrome. 61
28148925 2017
Spondyloepimetaphyseal dysplasia with neurodegeneration associated with AIFM1 mutation - a novel phenotype of the mitochondrial disease. 61
27102849 2017
Opitz award-winning paper details genetic cause of CODAS syndrome: Research points to new categories of rare disorder. 61
27643968 2016
Emerging role of Lon protease as a master regulator of mitochondrial functions. 61
27033304 2016
Mutations in LONP1, a mitochondrial matrix protease, cause CODAS syndrome. 61
25808063 2015
[CODAS syndrome]. 61
11462519 2001

Variations for Codas Syndrome

ClinVar genetic disease variations for Codas Syndrome:

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 LONP1 NM_004793.4(LONP1):c.2353A>G (p.Arg785Gly)SNV Pathogenic 180657 rs730880293 19:5693748-5693748 19:5693737-5693737
2 LONP1 NM_004793.4(LONP1):c.2026C>T (p.Pro676Ser)SNV Pathogenic 180658 rs879255247 19:5694900-5694900 19:5694889-5694889
3 LONP1 NM_004793.4(LONP1):c.1892C>A (p.Ser631Tyr)SNV Pathogenic 180659 rs879255248 19:5696264-5696264 19:5696253-5696253
4 LONP1 NM_004793.4(LONP1):c.2171C>T (p.Ala724Val)SNV Pathogenic 180660 rs879255249 19:5694547-5694547 19:5694536-5694536
5 LONP1 NM_004793.4(LONP1):c.796C>G (p.Leu266Val)SNV Uncertain significance 547905 rs373284466 19:5711856-5711856 19:5711845-5711845
6 LONP1 NM_004793.4(LONP1):c.889G>A (p.Val297Met)SNV Uncertain significance 800802 19:5708396-5708396 19:5708385-5708385

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

# Symbol AA change Variation ID SNP ID
1 LONP1 p.Glu476Ala VAR_073338
2 LONP1 p.Ser631Tyr VAR_073339 rs879255248
3 LONP1 p.Ala670Val VAR_073340 rs770036526
4 LONP1 p.Arg672Cys VAR_073341 rs777009012
5 LONP1 p.Pro676Ser VAR_073342 rs879255247
6 LONP1 p.Arg679His VAR_073343 rs549574673
7 LONP1 p.Arg721Gly VAR_073344 rs147588238
8 LONP1 p.Ala724Val VAR_073345 rs879255249
9 LONP1 p.Pro749Ser VAR_073346
10 LONP1 p.Gly767Glu VAR_073347 rs562553348

Expression for Codas Syndrome

Search GEO for disease gene expression data for Codas Syndrome.

Pathways for Codas Syndrome

GO Terms for Codas Syndrome

Sources for Codas Syndrome

9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
31 HPO
32 ICD10
33 ICD10 via Orphanet
37 LifeMap
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
54 Novoseek
57 OMIM via Orphanet
61 PubMed
70 Tocris
72 UMLS via Orphanet
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