muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4
diseaseOn this page
Also known as FCMDFukuyama congenital muscular dystrophyFukuyama Type Congenital Muscular DystrophyMDDGA4muscle-eye-brain-FKTN relatedmuscular dystrophy-dystroglycanopathy (congenital with Brain and eye anomalies) type A, 4Walker-Warburg syndrome or muscle-eye-brain disease, FKTN-related
Summary
muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4 (MONDO:0009678) is a disease caused by FKTN (GenCC Definitive), with 3 cohort genes.
At a glance
- Prevalence: Unknown (Worldwide) [Orphanet-validated]
- Causal gene: FKTN (GenCC Definitive)
- Cohort genes: 3
- ClinVar variants: 236
- Phenotypes (HPO): 31
Clinical features
Epidemiology
Prevalence records
1 prevalence record(s), Orphanet:
| Type | Class | Value | Geography | Validation |
|---|---|---|---|---|
| Prevalence at birth | 1-9 / 100 000 | 2.8 | Japan | Validated |
Signs & symptoms
Clinical features (HPO)
31 HPO clinical features (Orphanet curated; top 31 by frequency):
| HPO ID | Term | Frequency |
|---|---|---|
| HP:0000298 | Mask-like facies | Very frequent (80-99%) |
| HP:0000750 | Delayed speech and language development | Very frequent (80-99%) |
| HP:0001252 | Hypotonia | Very frequent (80-99%) |
| HP:0001263 | Global developmental delay | Very frequent (80-99%) |
| HP:0001288 | Gait disturbance | Very frequent (80-99%) |
| HP:0001357 | Plagiocephaly | Very frequent (80-99%) |
| HP:0001371 | Flexion contracture | Very frequent (80-99%) |
| HP:0003198 | Myopathy | Very frequent (80-99%) |
| HP:0003457 | EMG abnormality | Very frequent (80-99%) |
| HP:0003560 | Muscular dystrophy | Very frequent (80-99%) |
| HP:0007260 | Type II lissencephaly | Very frequent (80-99%) |
| HP:0010864 | Intellectual disability, severe | Very frequent (80-99%) |
| HP:0030046 | Hypoglycosylation of alpha-dystroglycan | Very frequent (80-99%) |
| HP:0000238 | Hydrocephalus | Frequent (30-79%) |
| HP:0000248 | Brachycephaly | Frequent (30-79%) |
| HP:0000545 | Myopia | Frequent (30-79%) |
| HP:0000767 | Pectus excavatum | Frequent (30-79%) |
| HP:0001250 | Seizure | Frequent (30-79%) |
| HP:0001612 | Weak cry | Frequent (30-79%) |
| HP:0002119 | Ventriculomegaly | Frequent (30-79%) |
| HP:0002353 | EEG abnormality | Frequent (30-79%) |
| HP:0100490 | Camptodactyly of finger | Frequent (30-79%) |
| HP:0000268 | Dolichocephaly | Occasional (5-29%) |
| HP:0000501 | Glaucoma | Occasional (5-29%) |
| HP:0000505 | Visual impairment | Occasional (5-29%) |
| HP:0000518 | Cataract | Occasional (5-29%) |
| HP:0000648 | Optic atrophy | Occasional (5-29%) |
| HP:0001511 | Intrauterine growth retardation | Occasional (5-29%) |
| HP:0001644 | Dilated cardiomyopathy | Occasional (5-29%) |
| HP:0007370 | Aplasia/Hypoplasia of the corpus callosum | Occasional (5-29%) |
| HP:0007973 | Retinal dysplasia | Occasional (5-29%) |
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4 |
| Mondo ID | MONDO:0009678 |
| OMIM | 253800 |
| Orphanet | 272 |
| DOID | DOID:0050559 |
| NCIT | C126741 |
| SNOMED CT | 111502003 |
| UMLS | C0410174 |
| MedGen | 140820 |
| GARD | 0006475 |
| NORD | 1169 |
| Is cancer (heuristic) | no |
Also known as: FCMD · Fukuyama congenital muscular dystrophy · Fukuyama Type Congenital Muscular Dystrophy · MDDGA4 · muscle-eye-brain-FKTN related · muscular dystrophy-dystroglycanopathy (congenital with Brain and eye anomalies) type A, 4 · muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4 · Walker-Warburg syndrome or muscle-eye-brain disease, FKTN-related
Data availability: 236 ClinVar variants · 4 GenCC gene-disease records · 3 cell lines.
Disease family
Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › congenital muscular dystrophy › muscular dystrophy-dystroglycanopathy › muscular dystrophy-dystroglycanopathy, type A › muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4
Related subtypes (13): muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A3, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A5, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A6, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 10, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 11, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A13, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A14, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9
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
236 retrieved; paginated sample, class counts are floors:
100 uncertain significance, 56 conflicting classifications of pathogenicity, 32 likely pathogenic, 17 pathogenic/likely pathogenic, 15 pathogenic, 13 benign/likely benign, 3 likely benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1075765 | NM_001079802.2(FKTN):c.567_568delinsTT (p.Leu189_Arg190delinsPheTer) | FKTN | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1252030 | NM_001079802.2(FKTN):c.78C>G (p.Tyr26Ter) | FKTN | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 167069 | NM_001079802.2(FKTN):c.411C>A (p.Cys137Ter) | FKTN | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1970586 | NM_001079802.2(FKTN):c.164G>A (p.Trp55Ter) | FKTN | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 225359 | NM_001079802.2(FKTN):c.607C>T (p.Arg203Ter) | FKTN | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 281839 | NM_001079802.2(FKTN):c.330dup (p.Thr111fs) | FKTN | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 283622 | NM_001079802.2(FKTN):c.456_457del (p.Ser154fs) | FKTN | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 3199 | NM_006731.2(FKTN):c.*4392_*4393ins[AB185332.1] | FKTN | Pathogenic | no assertion criteria provided |
| 3200 | NM_001079802.2(FKTN):c.139C>T (p.Arg47Ter) | FKTN | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 3201 | NM_001079802.2(FKTN):c.187_188del (p.Met63fs) | FKTN | Pathogenic | criteria provided, single submitter |
| 3202 | NM_006731.2:c.911-24_911-23insN[1200] | FKTN | Pathogenic | no assertion criteria provided |
| 3203 | NM_001079802.2(FKTN):c.1167dup (p.Phe390fs) | FKTN | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 3205 | NM_001079802.2(FKTN):c.454dup (p.Ser152fs) | FKTN | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 3206 | NM_001079802.2(FKTN):c.346C>T (p.Gln116Ter) | FKTN | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 3208 | NM_001079802.2(FKTN):c.920G>A (p.Arg307Gln) | FKTN | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 3212 | NM_001079802.2(FKTN):c.*5374_*5846del | FKTN | Pathogenic | no assertion criteria provided |
| 3216 | NM_001079802.2(FKTN):c.919C>T (p.Arg307Ter) | FKTN | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 3596214 | NM_001079802.2(FKTN):c.1045-6C>G | FKTN | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 370133 | NM_001079802.2(FKTN):c.429del (p.Asp144fs) | FKTN | Pathogenic | criteria provided, single submitter |
| 370768 | NM_001079802.2(FKTN):c.109G>T (p.Gly37Ter) | FKTN | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 371091 | NM_001079802.2(FKTN):c.1106del (p.Phe369fs) | FKTN | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 496331 | NM_001079802.2(FKTN):c.648-1243G>T | FKTN | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 555661 | NM_001079802.2(FKTN):c.42del (p.Thr14_Leu15insTer) | FKTN | Pathogenic | criteria provided, single submitter |
| 556831 | NM_001079802.2(FKTN):c.1099del (p.Val367fs) | FKTN | Pathogenic | criteria provided, single submitter |
| 557908 | NM_001079802.2(FKTN):c.1129_1130del (p.Met377fs) | FKTN | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 558161 | NM_001079802.2(FKTN):c.1172+1G>A | FKTN | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 558217 | NM_001079802.2(FKTN):c.1264_1286del (p.Asn422fs) | FKTN | Pathogenic | criteria provided, single submitter |
| 596647 | NM_001079802.2(FKTN):c.369+1G>C | FKTN | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 654926 | NM_001079802.2(FKTN):c.1261_1286delinsACC (p.Ala421fs) | FKTN | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 666969 | NM_001079802.2(FKTN):c.528dup (p.His177fs) | FKTN | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 13 · Orphanet: 12 · 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 |
|---|---|---|---|---|
| FKTN | Definitive | Autosomal recessive | muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4 | 13 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| FKTN | Orphanet:154 | Familial isolated dilated cardiomyopathy |
| FKTN | Orphanet:206554 | Fukutin-related limb-girdle muscular dystrophy R13 |
| FKTN | Orphanet:272 | Congenital muscular dystrophy, Fukuyama type |
| FKTN | Orphanet:370980 | Congenital muscular dystrophy without intellectual disability |
| FKTN | Orphanet:588 | Muscle-eye-brain disease |
| FKTN | Orphanet:899 | Walker-Warburg syndrome |
| FKRP | Orphanet:34515 | FKRP-related limb-girdle muscular dystrophy R9 |
| FKRP | Orphanet:370959 | Congenital muscular dystrophy with cerebellar involvement |
| FKRP | Orphanet:370968 | Congenital muscular dystrophy with intellectual disability |
| FKRP | Orphanet:370980 | Congenital muscular dystrophy without intellectual disability |
| FKRP | Orphanet:588 | Muscle-eye-brain disease |
| FKRP | Orphanet:899 | Walker-Warburg syndrome |
Cohort genes → proteins
3 cohort genes, 3 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 3 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| FKTN | HGNC:3622 | ENSG00000106692 | O75072 | Ribitol-5-phosphate transferase FKTN | gencc,clinvar |
| FKRP | HGNC:17997 | ENSG00000181027 | Q9H9S5 | Ribitol 5-phosphate transferase FKRP | clinvar |
| MYH1 | HGNC:7567 | ENSG00000109061 | P12882 | Myosin-1 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| FKTN | Ribitol-5-phosphate transferase FKTN | Catalyzes the transfer of a ribitol-phosphate from CDP-ribitol to the distal N-acetylgalactosamine of the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-beta-3-N-acetylglucosamine-beta-4-(phosphate-6-)mannose), a carbohydra… |
| FKRP | Ribitol 5-phosphate transferase FKRP | Catalyzes the transfer of a ribitol 5-phosphate from CDP-L-ribitol to the ribitol 5-phosphate previously attached by FKTN/fukutin to the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-beta-3-N-acetylglucosamine-beta-4-(phos… |
| MYH1 | Myosin-1 | Required for normal hearing. |
Protein-family classification
Druggable: 0 · Difficult: 1 · Unknown: 2 · Druggable fraction: 0.0
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 |
|---|---|---|---|
| Scaffold/PPI | 1 | 5.8× | 0.327 |
| Other/Unknown | 2 | 1.2× | 0.587 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| FKTN | Other/Unknown | no | LicD/FKTN/FKRP_NTP_transf, FKTN/MNN-like, FKTN_N | |
| FKRP | Other/Unknown | no | LicD/FKTN/FKRP_NTP_transf, LicD_transferase, FKRP_N | |
| MYH1 | Scaffold/PPI | no | IQ_motif_EF-hand-BS, Myosin_head_motor_dom-like, Myosin_tail |
Expression context
Cohort genes with no expression data: 0.
2 cohort genes 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) | 3 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| adrenal tissue | 1 |
| calcaneal tendon | 1 |
| germinal epithelium of ovary | 1 |
| cardiac muscle of right atrium | 1 |
| hindlimb stylopod muscle | 1 |
| left ventricle myocardium | 1 |
| biceps brachii | 1 |
| skeletal muscle tissue of rectus abdominis | 1 |
| vastus lateralis | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| FKTN | 277 | ubiquitous | yes | calcaneal tendon, adrenal tissue, germinal epithelium of ovary |
| FKRP | 230 | ubiquitous | marker | left ventricle myocardium, cardiac muscle of right atrium, hindlimb stylopod muscle |
| MYH1 | 151 | tissue_specific | marker | skeletal muscle tissue of rectus abdominis, biceps brachii, vastus lateralis |
Protein interactions among cohort
Intra-cohort edges: 1.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| MYH1 | 2,004 |
| FKRP | 1,436 |
| FKTN | 1,226 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| FKRP | FKTN | intact, string_interaction |
Structural data
PDB: 1 · AlphaFold-only: 2 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| FKRP | Q9H9S5 | 8 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| FKTN | O75072 | 92.48 |
| MYH1 | P12882 | 73.85 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 3 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Matriglycan biosynthesis on DAG1 | 2 | 815.7× | 1e-06 | FKTN, FKRP |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| skeletal muscle fiber differentiation | 2 | 1123.5× | 4e-05 | FKTN, FKRP |
| protein O-linked glycosylation via mannose | 2 | 624.1× | 7e-05 | FKTN, FKRP |
| basement membrane organization | 2 | 340.4× | 2e-04 | FKTN, FKRP |
| muscle contraction | 2 | 138.7× | 8e-04 | FKRP, MYH1 |
| pentitol metabolic process | 1 | 5617.3× | 0.001 | FKRP |
| filtration diaphragm assembly | 1 | 5617.3× | 0.001 | FKRP |
| pentose metabolic process | 1 | 2808.7× | 0.002 | FKRP |
| creatine metabolic process | 1 | 1404.3× | 0.003 | FKRP |
| connective tissue development | 1 | 1404.3× | 0.003 | FKRP |
| oxygen metabolic process | 1 | 1404.3× | 0.003 | FKRP |
| maintenance of protein localization in endoplasmic reticulum | 1 | 1123.5× | 0.004 | FKRP |
| localization of cell | 1 | 936.2× | 0.004 | FKRP |
| connective tissue replacement | 1 | 802.5× | 0.004 | FKRP |
| cerebellar cortex development | 1 | 702.2× | 0.005 | FKTN |
| diaphragm development | 1 | 624.1× | 0.005 | FKRP |
| protein import | 1 | 561.7× | 0.005 | FKRP |
| response to alcohol | 1 | 510.7× | 0.005 | FKRP |
| reelin-mediated signaling pathway | 1 | 401.2× | 0.006 | FKRP |
| respiratory system process | 1 | 312.1× | 0.007 | FKRP |
| glial cell differentiation | 1 | 295.6× | 0.007 | FKRP |
| skeletal muscle tissue regeneration | 1 | 295.6× | 0.007 | FKRP |
| protein tetramerization | 1 | 208.1× | 0.010 | FKRP |
| negative regulation of JNK cascade | 1 | 187.2× | 0.010 | FKTN |
| neuromuscular process | 1 | 175.5× | 0.011 | FKRP |
| adult walking behavior | 1 | 165.2× | 0.011 | FKRP |
| glycolytic process | 1 | 127.7× | 0.013 | FKRP |
| heart morphogenesis | 1 | 124.8× | 0.013 | FKRP |
| camera-type eye development | 1 | 119.5× | 0.013 | FKRP |
| response to activity | 1 | 108.0× | 0.014 | FKRP |
| response to glucocorticoid | 1 | 108.0× | 0.014 | FKRP |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 3
Druggability breadth: 0 of 3 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 |
|---|---|---|
| FKTN | 0 | 0 |
| FKRP | 0 | 0 |
| MYH1 | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 0.
Pharmacogenomics
Cohort genes with a PharmGKB record: 3; 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 | 0 | |
| E | Difficult family or no structure, no drug | 3 | FKTN, FKRP, MYH1 |
Undrugged target profiles
3 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| FKTN | 0 | — |
| FKRP | 0 | — |
| MYH1 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.