CAGSSS
MCID: CTR140
MIFTS: 33

Cataracts, Growth Hormone Deficiency, Sensory Neuropathy, Sensorineural Hearing Loss, and Skeletal Dysplasia (CAGSSS)

Categories: Bone diseases, Ear diseases, Endocrine diseases, Eye diseases, Fetal diseases, Genetic diseases, Metabolic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Cataracts, Growth Hormone Deficiency, Sensory Neuropathy,...

MalaCards integrated aliases for Cataracts, Growth Hormone Deficiency, Sensory Neuropathy, Sensorineural Hearing Loss, and Skeletal Dysplasia:

Name: Cataracts, Growth Hormone Deficiency, Sensory Neuropathy, Sensorineural Hearing Loss, and Skeletal Dysplasia 57 72 29 6 39 70
Cagsss 57 58 72
Cataract-Growth Hormone Deficiency-Sensory Neuropathy-Sensorineural Hearing Loss-Skeletal Dysplasia Syndrome 58
Cagsss Syndrome 36

Characteristics:

Orphanet epidemiological data:

58
cataract-growth hormone deficiency-sensory neuropathy-sensorineural hearing loss-skeletal dysplasia syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood,Infancy;

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive

Miscellaneous:
highly variable phenotype
not all patients have all features
onset in infancy, but features may appear over time
family a presented with early-onset intractable seizures and cortical abnormalities


HPO:

31
cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare eye diseases
Rare otorhinolaryngological diseases
Rare bone diseases
Inborn errors of metabolism
Rare endocrine diseases
Developmental anomalies during embryogenesis


Summaries for Cataracts, Growth Hormone Deficiency, Sensory Neuropathy,...

OMIM® : 57 CAGSSS, which comprises cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia, is an autosomal recessive multisystemic disorder with a highly variable phenotypic spectrum. Not all of these features are always present, and almost all the features may present at different times and/or become more apparent with age. The skeletal features are consistent with spondyloepimetaphyseal dysplasia (SEMD) (summary by Vona et al., 2018). One family had a distinctive presentation with infantile-onset intractable seizures and cortical abnormalities reminiscent of Leigh syndrome (see 256000). The correlation between genotype and phenotype remains unclear, but since the IARS2 gene is involved in mitochondrial function, heterogeneous manifestations can be expected (Takezawa et al., 2018). (616007) (Updated 20-May-2021)

MalaCards based summary : Cataracts, Growth Hormone Deficiency, Sensory Neuropathy, Sensorineural Hearing Loss, and Skeletal Dysplasia, also known as cagsss, is related to leigh syndrome and ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus. An important gene associated with Cataracts, Growth Hormone Deficiency, Sensory Neuropathy, Sensorineural Hearing Loss, and Skeletal Dysplasia is IARS2 (Isoleucyl-TRNA Synthetase 2, Mitochondrial), and among its related pathways/superpathways is Aminoacyl-tRNA biosynthesis. Affiliated tissues include eye, pituitary and bone, and related phenotypes are thick eyebrow and short stature

KEGG : 36 Cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia (CAGSSS) is a very rare autosomal recessive disorder. It has been reported that mutations in IARS2 are associated with this disease. IARS2 encodes the mitochondrial isoleucine-tRNA synthetase.

UniProtKB/Swiss-Prot : 72 Cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia: An autosomal recessive disorder characterized by cataracts, short- stature secondary to growth hormone deficiency, sensorineural hearing deficit, peripheral sensory neuropathy, skeletal dysplasia, scoliosis, and facial dysmorphism.

Related Diseases for Cataracts, Growth Hormone Deficiency, Sensory Neuropathy,...

Diseases related to Cataracts, Growth Hormone Deficiency, Sensory Neuropathy, Sensorineural Hearing Loss, and Skeletal Dysplasia via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 12)
# Related Disease Score Top Affiliating Genes
1 leigh syndrome 10.0
2 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.0
3 sensorineural hearing loss 10.0
4 sensory peripheral neuropathy 10.0
5 cataract 10.0
6 growth hormone deficiency 10.0
7 west syndrome 9.9
8 spondyloepimetaphyseal dysplasia 9.9
9 osteochondrodysplasia 9.9
10 peripheral nervous system disease 9.9
11 neuropathy 9.9
12 specific language disorder 9.9

Graphical network of the top 20 diseases related to Cataracts, Growth Hormone Deficiency, Sensory Neuropathy, Sensorineural Hearing Loss, and Skeletal Dysplasia:



Diseases related to Cataracts, Growth Hormone Deficiency, Sensory Neuropathy, Sensorineural Hearing Loss, and Skeletal Dysplasia

Symptoms & Phenotypes for Cataracts, Growth Hormone Deficiency, Sensory Neuropathy,...

Human phenotypes related to Cataracts, Growth Hormone Deficiency, Sensory Neuropathy, Sensorineural Hearing Loss, and Skeletal Dysplasia:

58 31 (show top 50) (show all 56)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 thick eyebrow 58 31 hallmark (90%) Very frequent (99-80%) HP:0000574
2 short stature 58 31 hallmark (90%) Very frequent (99-80%) HP:0004322
3 prominent forehead 58 31 hallmark (90%) Very frequent (99-80%) HP:0011220
4 genu valgum 58 31 hallmark (90%) Very frequent (99-80%) HP:0002857
5 motor delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0001270
6 achalasia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002571
7 narrow mouth 58 31 hallmark (90%) Very frequent (99-80%) HP:0000160
8 hip dislocation 58 31 hallmark (90%) Very frequent (99-80%) HP:0002827
9 peripheral neuropathy 58 31 hallmark (90%) Very frequent (99-80%) HP:0009830
10 developmental cataract 58 31 hallmark (90%) Very frequent (99-80%) HP:0000519
11 bilateral sensorineural hearing impairment 58 31 hallmark (90%) Very frequent (99-80%) HP:0008619
12 progressive sensorineural hearing impairment 58 31 hallmark (90%) Very frequent (99-80%) HP:0000408
13 thoracic kyphoscoliosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0005659
14 periarticular subcutaneous nodules 58 31 hallmark (90%) Very frequent (99-80%) HP:0007470
15 spondyloepiphyseal dysplasia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002655
16 fasting hypoglycemia 58 31 hallmark (90%) Very frequent (99-80%) HP:0003162
17 prelingual sensorineural hearing impairment 58 31 hallmark (90%) Very frequent (99-80%) HP:0000399
18 cervical spinal canal stenosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0008445
19 decreased response to growth hormone stimuation test 31 hallmark (90%) HP:0000824
20 scoliosis 58 31 Very frequent (99-80%) HP:0002650
21 cataract 58 31 Very frequent (99-80%) HP:0000518
22 sensorineural hearing impairment 58 31 Very frequent (99-80%) HP:0000407
23 spinal canal stenosis 58 31 Very frequent (99-80%) HP:0003416
24 ptosis 31 HP:0000508
25 nystagmus 31 HP:0000639
26 osteopenia 31 HP:0000938
27 hyperlordosis 31 HP:0003307
28 global developmental delay 31 HP:0001263
29 skeletal dysplasia 58 Very frequent (99-80%)
30 depressed nasal bridge 31 HP:0005280
31 mandibular prognathia 31 HP:0000303
32 pes planus 31 HP:0001763
33 abnormal vertebral morphology 31 HP:0003468
34 flexion contracture 31 HP:0001371
35 congenital hip dislocation 31 HP:0001374
36 cerebral cortical atrophy 31 HP:0002120
37 brachydactyly 31 HP:0001156
38 long philtrum 31 HP:0000343
39 deeply set eye 31 HP:0000490
40 sensory neuropathy 31 HP:0000763
41 hyporeflexia 31 HP:0001265
42 thin vermilion border 31 HP:0000233
43 midface retrusion 31 HP:0011800
44 tapered finger 31 HP:0001182
45 keratoconjunctivitis sicca 31 HP:0001097
46 generalized hypotonia 31 HP:0001290
47 distal sensory impairment 31 HP:0002936
48 growth hormone deficiency 58 Very frequent (99-80%)
49 esotropia 31 HP:0000565
50 hypsarrhythmia 31 HP:0002521

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Skeletal Spine:
scoliosis
lordosis
abnormal vertebral bodies
spinal stenosis

Skeletal:
osteopenia
spondyloepimetaphyseal dysplasia
joint contractures
delayed ossification

Skeletal Feet:
pes planus

Skeletal Pelvis:
congenital hip dislocation
deformities of the femoral head

Head And Neck Face:
long philtrum
flat forehead
midface hypoplasia
prognathism
dysmorphic features, variable
more
Endocrine Features:
growth hormone deficiency
central adrenal insufficiency (2 patients)

Head And Neck Ears:
sensorineural hearing loss

Skeletal Limbs:
genu valgus
irregular metaphyses
shortened long bones
flared metaphyses

Muscle Soft Tissue:
hypotonia (family a)

Head And Neck Eyes:
ptosis
strabismus
esotropia
thick eyebrows
cataracts
more
Head And Neck Nose:
depressed nasal bridge

Growth Height:
short stature

Skeletal Hands:
brachydactyly
tapering fingers

Neurologic Peripheral Nervous System:
hyporeflexia
distal sensory impairment
sensorimotor neuropathy
loss of myelinated fibers seen on sural nerve biopsy

Neurologic Central Nervous System:
delayed motor development
intractable seizures (family a)
hypsarrhythmia seen on eeg (family a)
t2-weighted abnormalities in the basal ganglia (family a)
leigh syndrome (family a)
more
Head And Neck Mouth:
thin lips
lack of fungiform papillae (2 patients)

Abdomen Gastrointestinal:
type ii esophageal achalasia (2 patients)

Clinical features from OMIM®:

616007 (Updated 20-May-2021)

Drugs & Therapeutics for Cataracts, Growth Hormone Deficiency, Sensory Neuropathy,...

Search Clinical Trials , NIH Clinical Center for Cataracts, Growth Hormone Deficiency, Sensory Neuropathy, Sensorineural Hearing Loss, and Skeletal Dysplasia

Genetic Tests for Cataracts, Growth Hormone Deficiency, Sensory Neuropathy,...

Genetic tests related to Cataracts, Growth Hormone Deficiency, Sensory Neuropathy, Sensorineural Hearing Loss, and Skeletal Dysplasia:

# Genetic test Affiliating Genes
1 Cataracts, Growth Hormone Deficiency, Sensory Neuropathy, Sensorineural Hearing Loss, and Skeletal Dysplasia 29 IARS2

Anatomical Context for Cataracts, Growth Hormone Deficiency, Sensory Neuropathy,...

MalaCards organs/tissues related to Cataracts, Growth Hormone Deficiency, Sensory Neuropathy, Sensorineural Hearing Loss, and Skeletal Dysplasia:

40
Eye, Pituitary, Bone

Publications for Cataracts, Growth Hormone Deficiency, Sensory Neuropathy,...

Articles related to Cataracts, Growth Hormone Deficiency, Sensory Neuropathy, Sensorineural Hearing Loss, and Skeletal Dysplasia:

# Title Authors PMID Year
1
Novel IARS2 mutations in Japanese siblings with CAGSSS, Leigh, and West syndrome. 61 6 57
30041933 2018
2
Expanding the clinical phenotype of IARS2-related mitochondrial disease. 6 57 61
30419932 2018
3
Confirmation of CAGSSS syndrome as a distinct entity in a Danish patient with a novel homozygous mutation in IARS2. 6 57 61
28328135 2017
4
Mutation in the nuclear-encoded mitochondrial isoleucyl-tRNA synthetase IARS2 in patients with cataracts, growth hormone deficiency with short stature, partial sensorineural deafness, and peripheral neuropathy or with Leigh syndrome. 57 6
25130867 2014
5
Unique hereditary sensory and autonomic neuropathy with growth hormone deficiency. 6 57
8409271 1993
6
Recessive Mutation in a Nuclear-Encoded Mitochondrial tRNA Synthetase Associated With Infantile Cataract, Congenital Neurotrophic Keratitis, and Orbital Myopathy. 57 61
27078007 2016
7
Does IARS2 deficiency cause an intrinsic disorder of bone development (skeletal dysplasia) or are the reported skeletal changes secondary to growth hormone deficiency and neuromuscular involvement? 57
25771764 2015
8
Response to: does IARS2 deficiency cause an intrinsic disorder of bone development (skeletal dysplasia) or are the reported skeletal changes secondary to growth hormone deficiency and neuromuscular involvement? 57
25771765 2015

Variations for Cataracts, Growth Hormone Deficiency, Sensory Neuropathy,...

ClinVar genetic disease variations for Cataracts, Growth Hormone Deficiency, Sensory Neuropathy, Sensorineural Hearing Loss, and Skeletal Dysplasia:

6 (show all 13)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 IARS2 NM_018060.4(IARS2):c.2620G>A (p.Gly874Arg) SNV Pathogenic 638568 rs151241066 GRCh37: 1:220316345-220316345
GRCh38: 1:220143003-220143003
2 IARS2 NM_018060.4(IARS2):c.680T>C (p.Phe227Ser) SNV Pathogenic 638569 rs1571845061 GRCh37: 1:220275600-220275600
GRCh38: 1:220102258-220102258
3 IARS2 NM_018060.4(IARS2):c.2450G>A (p.Arg817His) SNV Pathogenic 638570 rs146618526 GRCh37: 1:220315180-220315180
GRCh38: 1:220141838-220141838
4 IARS2 NM_018060.4(IARS2):c.2725C>T (p.Pro909Ser) SNV Pathogenic 638571 rs1571865562 GRCh37: 1:220316450-220316450
GRCh38: 1:220143108-220143108
5 IARS2 NM_018060.4(IARS2):c.2282A>G (p.His761Arg) SNV Pathogenic 638572 rs1571863769 GRCh37: 1:220312456-220312456
GRCh38: 1:220139114-220139114
6 IARS2 NM_018060.4(IARS2):c.2502dup (p.Ala835fs) Duplication Pathogenic 1028082 GRCh37: 1:220315228-220315229
GRCh38: 1:220141886-220141887
7 IARS2 NM_018060.4(IARS2):c.2726C>T (p.Pro909Leu) SNV Pathogenic 156553 rs587783070 GRCh37: 1:220316451-220316451
GRCh38: 1:220143109-220143109
8 IARS2 NM_018060.4(IARS2):c.1016C>T (p.Ser339Phe) SNV Uncertain significance 1032019 GRCh37: 1:220276854-220276854
GRCh38: 1:220103512-220103512
9 IARS2 NM_018060.4(IARS2):c.601C>T (p.Arg201Cys) SNV Uncertain significance 1032783 GRCh37: 1:220275521-220275521
GRCh38: 1:220102179-220102179
10 IARS2 NM_018060.4(IARS2):c.1255G>A (p.Asp419Asn) SNV Uncertain significance 801624 rs745601033 GRCh37: 1:220280421-220280421
GRCh38: 1:220107079-220107079
11 IARS2 NM_018060.4(IARS2):c.1504A>C (p.Ile502Leu) SNV Uncertain significance 587501 rs747014267 GRCh37: 1:220287680-220287680
GRCh38: 1:220114338-220114338
12 IARS2 NM_018060.4(IARS2):c.1821G>A (p.Trp607Ter) SNV Uncertain significance 156551 rs373436822 GRCh37: 1:220300169-220300169
GRCh38: 1:220126827-220126827
13 IARS2 NM_018060.4(IARS2):c.2122G>A (p.Glu708Lys) SNV Likely benign 156552 rs143722284 GRCh37: 1:220311332-220311332
GRCh38: 1:220137990-220137990

Expression for Cataracts, Growth Hormone Deficiency, Sensory Neuropathy,...

Search GEO for disease gene expression data for Cataracts, Growth Hormone Deficiency, Sensory Neuropathy, Sensorineural Hearing Loss, and Skeletal Dysplasia.

Pathways for Cataracts, Growth Hormone Deficiency, Sensory Neuropathy,...

Pathways related to Cataracts, Growth Hormone Deficiency, Sensory Neuropathy, Sensorineural Hearing Loss, and Skeletal Dysplasia according to KEGG:

36
# Name Kegg Source Accession
1 Aminoacyl-tRNA biosynthesis hsa00970

GO Terms for Cataracts, Growth Hormone Deficiency, Sensory Neuropathy,...

Sources for Cataracts, Growth Hormone Deficiency, Sensory Neuropathy,...

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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