Bilateral generalized polymicrogyria
diseaseOn this page
Also known as microcephaly, short stature, and polymicrogyria with seizuresMSSPPMGYSpolymicrogyria with seizures
Summary
Bilateral generalized polymicrogyria (MONDO:0013907) is a disease with 1 cohort gene.
At a glance
- Cohort genes: 1
- Phenotypes (HPO): 51
Clinical features
Signs & symptoms
Clinical features (HPO)
51 HPO clinical features (Orphanet curated; top 50 by frequency):
| HPO ID | Term | Frequency |
|---|---|---|
| HP:0002194 | Delayed gross motor development | Very frequent (80-99%) |
| HP:0012736 | Profound global developmental delay | Very frequent (80-99%) |
| HP:0031936 | Delayed ability to walk | Very frequent (80-99%) |
| HP:0000708 | Atypical behavior | Frequent (30-79%) |
| HP:0000733 | Abnormal repetitive mannerisms | Frequent (30-79%) |
| HP:0001257 | Spasticity | Frequent (30-79%) |
| HP:0002197 | Generalized-onset seizure | Frequent (30-79%) |
| HP:0002300 | Mutism | Frequent (30-79%) |
| HP:0002510 | Spastic tetraplegia | Frequent (30-79%) |
| HP:0008936 | Axial hypotonia | Frequent (30-79%) |
| HP:0010864 | Intellectual disability, severe | Frequent (30-79%) |
| HP:0011968 | Feeding difficulties | Frequent (30-79%) |
| HP:0100022 | Abnormality of movement | Frequent (30-79%) |
| HP:0100704 | Cerebral visual impairment | Frequent (30-79%) |
| HP:0000252 | Microcephaly | Occasional (5-29%) |
| HP:0000729 | Autistic behavior | Occasional (5-29%) |
| HP:0001256 | Intellectual disability, mild | Occasional (5-29%) |
| HP:0001332 | Dystonia | Occasional (5-29%) |
| HP:0001510 | Growth delay | Occasional (5-29%) |
| HP:0002020 | Gastroesophageal reflux | Occasional (5-29%) |
| HP:0002069 | Bilateral tonic-clonic seizure | Occasional (5-29%) |
| HP:0002079 | Hypoplasia of the corpus callosum | Occasional (5-29%) |
| HP:0002123 | Generalized myoclonic seizure | Occasional (5-29%) |
| HP:0002133 | Status epilepticus | Occasional (5-29%) |
| HP:0002187 | Intellectual disability, profound | Occasional (5-29%) |
| HP:0002342 | Intellectual disability, moderate | Occasional (5-29%) |
| HP:0002360 | Sleep abnormality | Occasional (5-29%) |
| HP:0004322 | Short stature | Occasional (5-29%) |
| HP:0005216 | Impaired mastication | Occasional (5-29%) |
| HP:0006956 | Dilation of lateral ventricles | Occasional (5-29%) |
| HP:0007166 | Paroxysmal dyskinesia | Occasional (5-29%) |
| HP:0007204 | Diffuse white matter abnormalities | Occasional (5-29%) |
| HP:0007359 | Focal-onset seizure | Occasional (5-29%) |
| HP:0007824 | Total ophthalmoplegia | Occasional (5-29%) |
| HP:0010553 | Oculogyric crisis | Occasional (5-29%) |
| HP:0010818 | Generalized tonic seizure | Occasional (5-29%) |
| HP:0010819 | Atonic seizure | Occasional (5-29%) |
| HP:0010821 | Focal emotional seizure with laughing | Occasional (5-29%) |
| HP:0011147 | Typical absence seizure | Occasional (5-29%) |
| HP:0011153 | Focal motor seizure | Occasional (5-29%) |
| HP:0011344 | Severe global developmental delay | Occasional (5-29%) |
| HP:0012469 | Infantile spasms | Occasional (5-29%) |
| HP:0012704 | Widened subarachnoid space | Occasional (5-29%) |
| HP:0025097 | Eyelid myoclonus | Occasional (5-29%) |
| HP:0025100 | Abnormal hippocampus morphology | Occasional (5-29%) |
| HP:0025517 | Hypoplastic hippocampus | Occasional (5-29%) |
| HP:0040288 | Nasogastric tube feeding | Occasional (5-29%) |
| HP:0100660 | Dyskinesia | Occasional (5-29%) |
| HP:0100716 | Self-injurious behavior | Occasional (5-29%) |
| HP:0200136 | Oral-pharyngeal dysphagia | Occasional (5-29%) |
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | bilateral generalized polymicrogyria |
| Mondo ID | MONDO:0013907 |
| Orphanet | 208447 |
| DOID | DOID:0080920 |
| UMLS | C5139324 |
| MedGen | 1684616 |
| GARD | 0010786 |
| Is cancer (heuristic) | no |
Also known as: bilateral generalized polymicrogyria · microcephaly, short stature, and polymicrogyria with seizures · MSSP · PMGYS · polymicrogyria with seizures
Data availability: 1 GenCC gene-disease record.
Disease family
Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › polymicrogyria › bilateral polymicrogyria › bilateral generalized polymicrogyria
Related subtypes (4): bilateral frontoparietal polymicrogyria, bilateral parasagittal parieto-occipital polymicrogyria, bilateral frontal polymicrogyria, bilateral perisylvian polymicrogyria
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
No tiered GWAS variants or ClinVar records for this disease.
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 |
|---|---|---|---|---|
| RTTN | Moderate | Autosomal recessive | bilateral generalized polymicrogyria | 6 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| RTTN | Orphanet:468631 | Microcephalic cortical malformations-short stature due to RTTN deficiency |
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 |
|---|---|---|---|---|---|
| RTTN | HGNC:18654 | ENSG00000176225 | Q86VV8 | Rotatin | gencc |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| RTTN | Rotatin | Involved in the genetic cascade that governs left-right specification. |
Protein-family classification
Druggable: 0 · Difficult: 0 · Unknown: 1 · 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 |
|---|---|---|---|
| Other/Unknown | 1 | 1.8× | 0.558 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| RTTN | Other/Unknown | no | ARM-like, ARM-type_fold, Rotatin_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 |
|---|---|
| male germ line stem cell (sensu Vertebrata) in testis | 1 |
| oocyte | 1 |
| secondary oocyte | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| RTTN | 238 | ubiquitous | marker | secondary oocyte, 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 |
|---|---|
| RTTN | 1,555 |
Structural data
PDB: 0 · AlphaFold-only: 1 · No structure: 0
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| RTTN | Q86VV8 | 77.49 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).
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 |
|---|---|---|---|---|
| ciliary basal body organization | 1 | 3370.4× | 0.001 | RTTN |
| centriole-centriole cohesion | 1 | 1296.3× | 0.002 | RTTN |
| centriole replication | 1 | 732.7× | 0.002 | RTTN |
| determination of left/right symmetry | 1 | 255.3× | 0.004 | RTTN |
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 |
|---|---|---|
| RTTN | 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 | 0 | |
| E | Difficult family or no structure, no drug | 1 | RTTN |
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) |
|---|---|---|
| RTTN | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.
Related Atlas pages
- Cohort genes: RTTN