Lhermitte-Duclos disease

Summary

Lhermitte-Duclos disease (MONDO:0019002) is a disease with 1 cohort gene and 1 clinical trial. Top therapeutic interventions include everolimus.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 2
• Phenotypes (HPO): 18
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		220	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

18 HPO clinical features (Orphanet curated; top 18 by frequency):

HPO ID	Term	Frequency
HP:0000158	Macroglossia	Very frequent (80-99%)
HP:0000238	Hydrocephalus	Very frequent (80-99%)
HP:0000256	Macrocephaly	Very frequent (80-99%)
HP:0001161	Hand polydactyly	Very frequent (80-99%)
HP:0001250	Seizure	Very frequent (80-99%)
HP:0001251	Ataxia	Very frequent (80-99%)
HP:0002017	Nausea and vomiting	Very frequent (80-99%)
HP:0002126	Polymicrogyria	Very frequent (80-99%)
HP:0002315	Headache	Very frequent (80-99%)
HP:0002516	Increased intracranial pressure	Very frequent (80-99%)
HP:0006824	Cranial nerve paralysis	Very frequent (80-99%)
HP:0012081	Enlarged cerebellum	Very frequent (80-99%)
HP:0200034	Papule	Very frequent (80-99%)
HP:0010619	Fibroadenoma of the breast	Frequent (30-79%)
HP:0012844	Trichilemmoma	Frequent (30-79%)
HP:0100031	Neoplasm of the thyroid gland	Frequent (30-79%)
HP:0100615	Ovarian neoplasm	Frequent (30-79%)
HP:0200016	Acrokeratosis	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Lhermitte-Duclos disease
Mondo ID	MONDO:0019002
Orphanet	65285
NCIT	C8419
UMLS	C0391826
MedGen	140251
GARD	0006901
Is cancer (heuristic)	no

Also known as: dysplastic cerebellar gangliocytoma · dysplastic gangliocytoma of cerebellum · dysplastic gangliocytoma of the cerebellum · LDD

Data availability: 2 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › nervous system neoplasm › neuroepithelial neoplasm › mixed neuronal-glial tumor › Lhermitte-Duclos disease

Related subtypes (11): ganglioneuroma, dysembryoplastic neuroepithelial tumor, extraventricular neurocytoma, gangliocytoma, desmoplastic infantile astrocytoma/ganglioglioma, ganglioglioma, papillary glioneuronal tumor, rosette-forming glioneuronal tumor of fourth ventricule, central neurocytoma, desmoplastic infantile astrocytoma, desmoplastic infantile ganglioglioma

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

2 retrieved; paginated sample, class counts are floors:

2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
7814	NM_000314.8(PTEN):c.469G>T (p.Glu157Ter)	PTEN	Pathogenic	reviewed by expert panel
7832	NM_000314.8(PTEN):c.335T>C (p.Leu112Pro)	PTEN	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 17 · Orphanet: 14 · 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
PTEN	Supportive	Autosomal dominant	Lhermitte-Duclos disease	17

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PTEN	Orphanet:109	Bannayan-Riley-Ruvalcaba syndrome
PTEN	Orphanet:137608	Segmental outgrowth-lipomatosis-arteriovenous malformation-epidermal nevus syndrome
PTEN	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
PTEN	Orphanet:201	Cowden syndrome
PTEN	Orphanet:210548	Macrocephaly-intellectual disability-autism syndrome
PTEN	Orphanet:2969	Proteus-like syndrome
PTEN	Orphanet:494547	Squamous cell carcinoma of the hypopharynx
PTEN	Orphanet:494550	Squamous cell carcinoma of the larynx
PTEN	Orphanet:500464	Squamous cell carcinoma of the nasal cavity and paranasal sinuses
PTEN	Orphanet:500478	Squamous cell carcinoma of the oropharynx
PTEN	Orphanet:502363	Squamous cell carcinoma of the oral cavity
PTEN	Orphanet:502366	Squamous cell carcinoma of the lip
PTEN	Orphanet:65285	Lhermitte-Duclos disease
PTEN	Orphanet:79076	Juvenile polyposis of infancy

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
PTEN	HGNC:9588	ENSG00000171862	P60484	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PTEN	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN	Dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins.

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
Phosphatase	1	83.9×	0.012

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PTEN	Phosphatase	yes	3.1.3.16	Tyr_Pase_dom, Tyr_Pase_cat, Tensin_C2-dom

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
calcaneal tendon	1
endothelial cell	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PTEN	256	ubiquitous	marker	sperm, endothelial cell, calcaneal tendon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PTEN	11,626

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PTEN	P60484	12

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. 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
PTEN Loss of Function in Cancer	1	5710.0×	0.002	PTEN
Regulation of PTEN mRNA translation	1	1142.0×	0.004	PTEN
Regulation of PTEN localization	1	1038.2×	0.004	PTEN
Synthesis of IP3 and IP4 in the cytosol	1	423.0×	0.007	PTEN
Transcriptional Regulation by MECP2	1	317.2×	0.007	PTEN
Negative regulation of the PI3K/AKT network	1	278.5×	0.007	PTEN
Ovarian tumor domain proteases	1	278.5×	0.007	PTEN
Synthesis of PIPs at the plasma membrane	1	211.5×	0.007	PTEN
Regulation of PTEN stability and activity	1	184.2×	0.007	PTEN
Regulation of PTEN gene transcription	1	178.4×	0.007	PTEN
TP53 Regulates Metabolic Genes	1	129.8×	0.008	PTEN
Downstream TCR signaling	1	128.3×	0.008	PTEN
Ub-specific processing proteases	1	53.1×	0.019	PTEN

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 synaptic vesicle clustering	1	8426.0×	0.002	PTEN
negative regulation of keratinocyte migration	1	5617.3×	0.002	PTEN
rhythmic synaptic transmission	1	4213.0×	0.002	PTEN
central nervous system myelin maintenance	1	2808.7×	0.002	PTEN
negative regulation of cell cycle G1/S phase transition	1	2407.4×	0.002	PTEN
negative regulation of wound healing, spreading of epidermal cells	1	2407.4×	0.002	PTEN
spindle assembly involved in female meiosis	1	1872.4×	0.002	PTEN
central nervous system neuron axonogenesis	1	1872.4×	0.002	PTEN
postsynaptic density assembly	1	1872.4×	0.002	PTEN
neuron-neuron synaptic transmission	1	1685.2×	0.002	PTEN
negative regulation of peptidyl-serine phosphorylation	1	1685.2×	0.002	PTEN
negative regulation of cell size	1	1685.2×	0.002	PTEN
presynaptic membrane assembly	1	1685.2×	0.002	PTEN
negative regulation of organ growth	1	1404.3×	0.002	PTEN
forebrain morphogenesis	1	1404.3×	0.002	PTEN
multicellular organismal response to stress	1	1296.3×	0.002	PTEN
negative regulation of axonogenesis	1	1296.3×	0.002	PTEN
cellular response to electrical stimulus	1	1296.3×	0.002	PTEN
negative regulation of excitatory postsynaptic potential	1	1296.3×	0.002	PTEN
maternal behavior	1	1123.5×	0.002	PTEN
prepulse inhibition	1	1123.5×	0.002	PTEN
locomotor rhythm	1	1053.2×	0.003	PTEN
synapse maturation	1	936.2×	0.003	PTEN
dendritic spine morphogenesis	1	887.0×	0.003	PTEN
negative regulation of focal adhesion assembly	1	766.0×	0.003	PTEN
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	702.2×	0.003	PTEN
negative regulation of vascular associated smooth muscle cell proliferation	1	674.1×	0.003	PTEN
phosphatidylinositol dephosphorylation	1	648.1×	0.003	PTEN
positive regulation of intracellular signal transduction	1	648.1×	0.003	PTEN
negative regulation of cellular senescence	1	648.1×	0.003	PTEN

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PTEN	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
PTEN	8	Binding:8

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PTEN	3.1.3.16, 3.1.3.67	protein-serine/threonine phosphatase, phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase

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	1	PTEN
D	Druggable family + AlphaFold only, no drug	0
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)
PTEN	8	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07218575	PHASE2/PHASE3	NOT_YET_RECRUITING	Double-Blind Trial of Everolimus for Improving Social Abilities in PTEN Germline Mutations

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
EVEROLIMUS	4	1