Bilateral polymicrogyria

Summary

Bilateral polymicrogyria (MONDO:0017091) is a disease (an umbrella term covering 5 Mondo subtypes) with 1 cohort gene.

At a glance

• Prevalence: Unknown (Worldwide)
• Umbrella term: 5 Mondo subtypes
• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 44

Clinical features

Signs & symptoms

Clinical features (HPO)

44 HPO clinical features (Orphanet curated; top 44 by frequency):

HPO ID	Term	Frequency
HP:0001250	Seizure	Very frequent (80-99%)
HP:0000565	Esotropia	Frequent (30-79%)
HP:0000750	Delayed speech and language development	Frequent (30-79%)
HP:0001256	Intellectual disability, mild	Frequent (30-79%)
HP:0001263	Global developmental delay	Frequent (30-79%)
HP:0001268	Mental deterioration	Frequent (30-79%)
HP:0001270	Motor delay	Frequent (30-79%)
HP:0001272	Cerebellar atrophy	Frequent (30-79%)
HP:0001285	Spastic tetraparesis	Frequent (30-79%)
HP:0002119	Ventriculomegaly	Frequent (30-79%)
HP:0002200	Pseudobulbar signs	Frequent (30-79%)
HP:0002342	Intellectual disability, moderate	Frequent (30-79%)
HP:0002463	Language impairment	Frequent (30-79%)
HP:0004302	Functional motor deficit	Frequent (30-79%)
HP:0007256	Abnormal pyramidal sign	Frequent (30-79%)
HP:0007359	Focal-onset seizure	Frequent (30-79%)
HP:0007362	Aplasia/Hypoplasia of the brainstem	Frequent (30-79%)
HP:0009878	Cerebellar ataxia associated with quadrupedal gait	Frequent (30-79%)
HP:0010522	Dyslexia	Frequent (30-79%)
HP:0011099	Spastic hemiparesis	Frequent (30-79%)
HP:0012429	Aplasia/Hypoplasia of the cerebral white matter	Frequent (30-79%)
HP:0100543	Cognitive impairment	Frequent (30-79%)
HP:0000154	Wide mouth	Occasional (5-29%)
HP:0000183	Tongue muscle weakness	Occasional (5-29%)
HP:0000256	Macrocephaly	Occasional (5-29%)
HP:0000347	Micrognathia	Occasional (5-29%)
HP:0000369	Low-set ears	Occasional (5-29%)
HP:0000407	Sensorineural hearing impairment	Occasional (5-29%)
HP:0001260	Dysarthria	Occasional (5-29%)
HP:0001349	Facial diplegia	Occasional (5-29%)
HP:0001762	Talipes equinovarus	Occasional (5-29%)
HP:0002069	Bilateral tonic-clonic seizure	Occasional (5-29%)
HP:0002123	Generalized myoclonic seizure	Occasional (5-29%)
HP:0002197	Generalized-onset seizure	Occasional (5-29%)
HP:0002307	Drooling	Occasional (5-29%)
HP:0002804	Arthrogryposis multiplex congenita	Occasional (5-29%)
HP:0006818	4-layered lissencephaly	Occasional (5-29%)
HP:0007024	Pseudobulbar paralysis	Occasional (5-29%)
HP:0011787	Central hypothyroidism	Occasional (5-29%)
HP:0011968	Feeding difficulties	Occasional (5-29%)
HP:0012469	Infantile spasms	Occasional (5-29%)
HP:0012650	Perisylvian polymicrogyria	Occasional (5-29%)
HP:0410011	Abnormality of masticatory muscle	Occasional (5-29%)
HP:3000047	Abnormal glossopharyngeal nerve morphology	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	bilateral polymicrogyria
Mondo ID	MONDO:0017091
Orphanet	268940
ICD-11	422828750
SNOMED CT	765757003
UMLS	C4707565
MedGen	1647593
GARD	0017269
Is cancer (heuristic)	no

Data availability: 1 ClinVar variant.

Disease family

An umbrella term covering 5 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › polymicrogyria › bilateral polymicrogyria

Related subtypes (1): unilateral polymicrogyria

Subtypes (5): bilateral frontoparietal polymicrogyria, bilateral parasagittal parieto-occipital polymicrogyria, bilateral generalized 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

ClinVar germline variants

1 retrieved; paginated sample, class counts are floors:

1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2672311	Single allele	BMP8B	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

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

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
BMP8B	HGNC:1075	ENSG00000116985	P34820	Bone morphogenetic protein 8B	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BMP8B	Bone morphogenetic protein 8B	Induces cartilage and bone formation.

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)
BMP8B	Other/Unknown	no		TGF-b_propeptide, TGF-b_C, TGF-beta-like

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
dorsal root ganglion	1
tibia	1
trigeminal ganglion	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BMP8B	218	broad	marker	tibia, dorsal root ganglion, trigeminal ganglion

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BMP8B	863

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
BMP8B	P34820	76.96

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
negative regulation of cell differentiation	1	285.6×	0.007	BMP8B
cartilage development	1	251.5×	0.007	BMP8B
ossification	1	227.7×	0.007	BMP8B
BMP signaling pathway	1	200.6×	0.007	BMP8B
skeletal system development	1	125.8×	0.010	BMP8B
cell differentiation	1	29.1×	0.034	BMP8B

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
BMP8B	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	BMP8B

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)
BMP8B	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.