Microcornea-myopic chorioretinal atrophy

Summary

Microcornea-myopic chorioretinal atrophy (MONDO:0014195) is a disease caused by ADAMTS18 (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: ADAMTS18 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 19

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		14	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	microcornea-myopic chorioretinal atrophy
Mondo ID	MONDO:0014195
OMIM	615458
Orphanet	369970
UMLS	C3809567
MedGen	815897
GARD	0017593
Is cancer (heuristic)	no

Also known as: microcornea, myopic chorioretinal atrophy, and telecanthus · microcornea-myopic chorioretinal atrophy · microcornea-myopic chorioretinal atrophy-telecanthus syndrome · MMCAT · MMCAT syndrome

Data availability: 19 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder › retinal degeneration › inherited retinal dystrophy › microcornea-myopic chorioretinal atrophy

Related subtypes (104): retinal dystrophies primarily involving Bruch’s membrane, vitreoretinal dystrophy, dystrophies primarily involving the retinal pigment epithelium, retinal dystrophy in systemic or cerebroretinal lipidoses, age-related macular degeneration, helicoid peripapillary chorioretinal degeneration, Sorsby fundus dystrophy, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, pigmented paravenous retinochoroidal atrophy, retinoschisis, autosomal dominant, retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations, amaurosis-hypertrichosis syndrome, familial benign flecked retina, microcephaly and chorioretinopathy 1, ornithine aminotransferase deficiency, retinal degeneration-nanophthalmos-glaucoma syndrome, retinoschisis of fovea, Revesz syndrome, choroideremia, choroideremia-deafness-obesity syndrome, X-linked retinal dysplasia, X-linked retinoschisis, progressive bifocal chorioretinal atrophy, aceruloplasminemia, late-onset retinal degeneration, infantile cerebellar-retinal degeneration, progressive retinal dystrophy due to retinol transport defect, retinal dystrophy with inner retinal dysfunction and ganglion cell anomalies, macular degeneration, early-onset, cone-rod dystrophy, ectopia lentis-chorioretinal dystrophy-myopia syndrome, foveal hypoplasia-presenile cataract syndrome, MRCS syndrome, X-linked intellectual disability-limb spasticity-retinal dystrophy-diabetes insipidus syndrome, Leber congenital amaurosis, oligocone trichromacy, Oguchi disease, retinitis pigmentosa, hereditary macular dystrophy, RPE65-related recessive retinopathy, RPGR-related retinopathy, AIPL1-related retinopathy, RP2-related retinopathy, RDH5-related retinopathy, RLBP1-related retinopathy, LCA5-related retinopathy, ATF6-related retinopathy, RAB28-related retinopathy, FLVCR1-related retinopathy with or without ataxia, RPE65-related dominant retinopathy, GUCY2D retinopathy, PDE6A-related retinopathy, ELOVL4-related maculopathy, MAK-related retinopathy, KIZ-related retinopathy, TOPORS-related retinopathy, PRPF8-related retinopathy, RD3-related retinopathy, BEST1-related dominant retinopathy, BEST1-related recessive retinopathy, IMPG2-related recessive retinopathy, IMPG2-related dominant retinopathy, CACNA1F-related retinopathy, CACNA2D4-related retinopathy, CDHR1-related retinopathy, GUCA1A-related retinopathy, RHO-related retinopathy, SNRNP200-related dominant retinopathy, RDH12-related recessive retinopathy, RDH12-related dominant retinopathy, NMNAT1-related retinopathy, CNGA3-related retinopathy, EYS-related retinopathy, GNAT2-related retinopathy, IDH3B-related retinopathy, MERTK-related retinopathy, PRPF31-related retinopathy, GPR179-related retinopathy, GRM6-related retinopathy, ADAM9-related retinopathy, RP1-related recessive retinopathy, RP1-related dominant retinopathy, CERKL-related retinopathy, TRPM1-related retinopathy, CNGB1-related retinopathy, PCARE-related retinopathy, CNGA1-related retinopathy, ABCA4-related retinopathy, NYX-related retinopathy, retinal dystrophy, X-linked, Gardner-Hardcastle type, PDE6C-related retinopathy, PDE6G-related retinopathy, LRIT3-related retinopathy, IMPG1-related dominant retinopathy, IMPG1-related recessive retinopathy, TTLL5-related retinopathy, HGSNAT-related retinopathy, IMPDH1-related retinopathy, PRPH2-related retinopathy, PROM1-related retinopathy, KCNV2-related retinopathy, CRX-related retinopathy, REEP6-related retinopathy, SPATA7-related retinopathy

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

19 retrieved; paginated sample, class counts are floors:

8 pathogenic, 4 uncertain significance, 3 likely pathogenic, 2 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1068894	NM_199355.4(ADAMTS18):c.3334C>T (p.Arg1112Ter)	ADAMTS18	Pathogenic	criteria provided, single submitter
1069609	NM_199355.4(ADAMTS18):c.3380G>A (p.Trp1127Ter)	ADAMTS18	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1456719	NM_199355.4(ADAMTS18):c.3139C>T (p.Arg1047Ter)	ADAMTS18	Pathogenic	criteria provided, single submitter
1936348	NM_199355.4(ADAMTS18):c.262C>T (p.Arg88Ter)	ADAMTS18	Pathogenic	criteria provided, multiple submitters, no conflicts
3775392	NM_199355.4(ADAMTS18):c.514C>T (p.Arg172Ter)	ADAMTS18	Pathogenic	criteria provided, single submitter
4531261	NM_199355.4(ADAMTS18):c.841C>T (p.Arg281Ter)	ADAMTS18	Pathogenic	criteria provided, single submitter
66040	NM_199355.4(ADAMTS18):c.2065G>T (p.Glu689Ter)	ADAMTS18	Pathogenic	no assertion criteria provided
66041	NM_199355.4(ADAMTS18):c.605T>C (p.Leu202Pro)	ADAMTS18	Pathogenic	no assertion criteria provided
66042	NM_199355.4(ADAMTS18):c.97C>T (p.Gln33Ter)	ADAMTS18	Pathogenic	no assertion criteria provided
1684629	Single allele	ADAMTS18	Likely pathogenic	criteria provided, single submitter
2431881	NC_0000016.10:g.(77282583_77329496)del	ADAMTS18	Likely pathogenic	criteria provided, single submitter
4849391	NM_199355.4(ADAMTS18):c.3274_3292del (p.Pro1092fs)	ADAMTS18	Likely pathogenic	criteria provided, single submitter
725287	NM_199355.4(ADAMTS18):c.3157C>T (p.Arg1053Trp)	ADAMTS18	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
841541	NM_199355.4(ADAMTS18):c.2752A>G (p.Lys918Glu)	ADAMTS18	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1017236	NM_199355.4(ADAMTS18):c.2519C>T (p.Thr840Met)	ADAMTS18	Uncertain significance	criteria provided, multiple submitters, no conflicts
2431465	NM_199355.4(ADAMTS18):c.1455C>A (p.Phe485Leu)	ADAMTS18	Uncertain significance	criteria provided, single submitter
66039	NM_199355.4(ADAMTS18):c.1731C>G (p.Cys577Trp)	ADAMTS18	Uncertain significance	criteria provided, single submitter
843787	NM_199355.4(ADAMTS18):c.1985C>G (p.Pro662Arg)	ADAMTS18	Uncertain significance	criteria provided, multiple submitters, no conflicts
803274	NM_199355.4(ADAMTS18):c.571T>C (p.Tyr191His)	ADAMTS18	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
ADAMTS18	Definitive	Autosomal recessive	microcornea-myopic chorioretinal atrophy	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ADAMTS18	Orphanet:369970	Microcornea-myopic chorioretinal atrophy-telecanthus syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ADAMTS18	HGNC:17110	ENSG00000140873	Q8TE60	A disintegrin and metalloproteinase with thrombospondin motifs 18	gencc,clinvar

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Protease	1	36.6×	0.027

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ADAMTS18	Protease	yes		TSP1_rpt, Peptidase_M12B, Peptidase_M12B_N

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cerebellar vermis	1
male germ line stem cell (sensu Vertebrata) in testis	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ADAMTS18	152	broad	marker	cerebellar vermis, secondary oocyte, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ADAMTS18	1,040

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ADAMTS18	Q8TE60	73.83

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective B3GALTL causes PpS	1	308.6×	0.016	ADAMTS18
O-glycosylation of TSR domain-containing proteins	1	300.5×	0.016	ADAMTS18
Diseases associated with O-glycosylation of proteins	1	215.5×	0.016	ADAMTS18
O-linked glycosylation	1	144.6×	0.016	ADAMTS18
Diseases of glycosylation	1	131.3×	0.016	ADAMTS18
Degradation of the extracellular matrix	1	117.7×	0.016	ADAMTS18
Diseases of metabolism	1	80.4×	0.020	ADAMTS18
Extracellular matrix organization	1	63.1×	0.022	ADAMTS18
Post-translational protein modification	1	19.2×	0.064	ADAMTS18
Disease	1	13.1×	0.081	ADAMTS18
Metabolism of proteins	1	12.4×	0.081	ADAMTS18

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of platelet aggregation	1	1404.3×	0.003	ADAMTS18
eye development	1	351.1×	0.006	ADAMTS18
extracellular matrix organization	1	122.1×	0.011	ADAMTS18
proteolysis	1	34.2×	0.029	ADAMTS18

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ADAMTS18	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	ADAMTS18
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
ADAMTS18	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.