Spastic diplegia

Summary

Spastic diplegia (MONDO:0001167) is a disease with 1 cohort gene and 19 clinical trials.

At a glance

• Cohort genes: 1
• Clinical trials: 19

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	spastic diplegia
Mondo ID	MONDO:0001167
MeSH	C537945
DOID	DOID:10965
ICD-11	563606390
NCIT	C34781
SNOMED CT	281411007, 58193001
UMLS	C0270804
MedGen	124371
Is cancer (heuristic)	no

Also known as: cerebral palsy spastic diplegic · diplegic infantile cerebral palsy · Little disease · Little’s disease

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › palsy › cerebral palsy › spastic cerebral palsy › spastic diplegia

Related subtypes (4): spastic hemiplegia, spastic monoplegia, spastic quadriplegic cerebral palsy, spastic triplegia

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: 8 · 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
ALK	Moderate	Autosomal dominant	spastic diplegia	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ALK	Orphanet:146	Differentiated thyroid carcinoma
ALK	Orphanet:178342	Inflammatory myofibroblastic tumor
ALK	Orphanet:251877	Ganglioneuroblastoma
ALK	Orphanet:251992	Ganglioneuroma
ALK	Orphanet:300895	ALK-positive anaplastic large cell lymphoma
ALK	Orphanet:364043	ALK-positive large B-cell lymphoma
ALK	Orphanet:626	Large/giant congenital melanocytic nevus
ALK	Orphanet:635	Neuroblastoma

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
ALK	HGNC:427	ENSG00000171094	Q9UM73	ALK tyrosine kinase receptor	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ALK	ALK tyrosine kinase receptor	Neuronal receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system.

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
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ALK	Kinase	yes	2.7.10.1	Prot_kinase_dom, MAM_dom, Ser-Thr/Tyr_kinase_cat_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
male germ cell	1
male germ line stem cell (sensu Vertebrata) in testis	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ALK	181	broad	marker	sperm, male germ cell, 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
ALK	4,792

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ALK	Q9UM73	79

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 17. 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
Drug resistance of ALK mutants	1	11420.0×	2e-04	ALK
ASP-3026-resistant ALK mutants	1	11420.0×	2e-04	ALK
NVP-TAE684-resistant ALK mutants	1	11420.0×	2e-04	ALK
alectinib-resistant ALK mutants	1	11420.0×	2e-04	ALK
brigatinib-resistant ALK mutants	1	11420.0×	2e-04	ALK
ceritinib-resistant ALK mutants	1	11420.0×	2e-04	ALK
crizotinib-resistant ALK mutants	1	11420.0×	2e-04	ALK
lorlatinib-resistant ALK mutants	1	11420.0×	2e-04	ALK
MDK and PTN in ALK signaling	1	2855.0×	7e-04	ALK
ALK mutants bind TKIs	1	951.7×	0.002	ALK
Signaling by ALK	1	571.0×	0.003	ALK
Signaling by ALK in cancer	1	271.9×	0.005	ALK
Signaling by ALK fusions and activated point mutants	1	150.3×	0.009	ALK
Diseases of signal transduction by growth factor receptors and second messengers	1	56.8×	0.021	ALK
Signaling by Receptor Tyrosine Kinases	1	51.7×	0.022	ALK
Disease	1	13.1×	0.081	ALK
Signal Transduction	1	10.2×	0.098	ALK

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
response to environmental enrichment	1	8426.0×	0.002	ALK
regulation of dopamine receptor signaling pathway	1	4213.0×	0.002	ALK
swimming behavior	1	3370.4×	0.002	ALK
response to stress	1	2407.4×	0.002	ALK
peptidyl-tyrosine autophosphorylation	1	1872.4×	0.002	ALK
phosphorylation	1	1296.3×	0.002	ALK
positive regulation of dendrite development	1	991.3×	0.003	ALK
negative regulation of lipid catabolic process	1	842.6×	0.003	ALK
regulation of neuron differentiation	1	732.7×	0.003	ALK
adult behavior	1	468.1×	0.004	ALK
energy homeostasis	1	271.8×	0.006	ALK
neuron development	1	255.3×	0.006	ALK
hippocampus development	1	230.8×	0.006	ALK
obsolete positive regulation of NF-kappaB transcription factor activity	1	205.5×	0.007	ALK
cell surface receptor protein tyrosine kinase signaling pathway	1	173.7×	0.007	ALK
protein autophosphorylation	1	145.3×	0.008	ALK
regulation of cell population proliferation	1	115.4×	0.010	ALK
regulation of apoptotic process	1	83.4×	0.013	ALK
signal transduction	1	16.1×	0.062	ALK

Therapeutics

Drug target analysis

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

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

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
ALK	CERITINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ALK	61	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CERITINIB	4	ALK
BOSUTINIB	4	ALK
CRIZOTINIB	4	ALK
ALECTINIB	4	ALK
ENTRECTINIB	4	ALK
LORLATINIB	4	ALK
GILTERITINIB	4	ALK
OSIMERTINIB	4	ALK
BRIGATINIB	4	ALK
REPOTRECTINIB	4	ALK
FEDRATINIB	4	ALK
RUXOLITINIB	4	ALK
INFIGRATINIB PHOSPHATE	4	ALK
INFIGRATINIB	4	ALK
PALBOCICLIB	4	ALK
VANDETANIB	4	ALK
UPADACITINIB	4	ALK
PAZOPANIB	4	ALK
NINTEDANIB	4	ALK
SUNITINIB	4	ALK
ERLOTINIB	4	ALK
MIDOSTAURIN	4	ALK
DACTOLISIB	3	ALK
LINIFANIB	3	ALK
SEMAXANIB	3	ALK
CANERTINIB	3	ALK
ROCILETINIB	3	ALK
ALVOCIDIB	3	ALK
CEDIRANIB	3	ALK
QUERCETIN	3	ALK

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
ALK	1,815	Binding:1801, Functional:13, ADMET:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ALK	2.7.10.1	receptor protein-tyrosine kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
ALK	1,815

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

30 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.

Compound	Max phase	Cohort target (bioactivity)
CERITINIB	4	ALK
BOSUTINIB	4	ALK
CRIZOTINIB	4	ALK
ALECTINIB	4	ALK
ENTRECTINIB	4	ALK
LORLATINIB	4	ALK
GILTERITINIB	4	ALK
OSIMERTINIB	4	ALK
BRIGATINIB	4	ALK
REPOTRECTINIB	4	ALK
FEDRATINIB	4	ALK
RUXOLITINIB	4	ALK
INFIGRATINIB PHOSPHATE	4	ALK
INFIGRATINIB	4	ALK
PALBOCICLIB	4	ALK
VANDETANIB	4	ALK
UPADACITINIB	4	ALK
PAZOPANIB	4	ALK
NINTEDANIB	4	ALK
SUNITINIB	4	ALK
ERLOTINIB	4	ALK
MIDOSTAURIN	4	ALK
DACTOLISIB	3	ALK
LINIFANIB	3	ALK
SEMAXANIB	3	ALK
CANERTINIB	3	ALK
ROCILETINIB	3	ALK
ALVOCIDIB	3	ALK
CEDIRANIB	3	ALK
QUERCETIN	3	ALK

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	ALK
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 19.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	17
PHASE3	1
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00632528	PHASE3	COMPLETED	MEOPA to Improve Physical Therapy Results After Multilevel Surgery
NCT00004751	PHASE2	UNKNOWN	Phase II Randomized Study of Selective Dorsal Rhizotomy and Physiotherapy Vs Physiotherapy Alone for Spastic Diplegia
NCT02535936	Not specified	RECRUITING	Cortical Plasticity in Spastic Diplegia After Selective Dorsal Rhizotomy
NCT03672877	Not specified	ACTIVE_NOT_RECRUITING	Randomized Controlled Trial of Early Intensive Leg Exercise to Improve Walking in Children With Diplegia
NCT06270550	Not specified	RECRUITING	Role of Dynamic Movement Intervention in Children with Spastic Diplegia
NCT06454656	Not specified	RECRUITING	A Motor Learning Intervention to Target Walking Performance in Ambulant Children With Cerebral Palsy
NCT06676332	Not specified	RECRUITING	Effect of Multisensory Motor Imagery Training on Muscle Performance and Coordination in Children With Spastic Diplegia
NCT07289347	Not specified	ACTIVE_NOT_RECRUITING	Effect of a Light Stimulated Footsteps Pathway on Gait in Spastic Children
NCT07433647	Not specified	RECRUITING	Evaluation of Brain MRI Changes in Cerebral Palsy Patients
NCT07438223	Not specified	RECRUITING	Effect Of Brain Gym Exercises On Balance And Quality Of Life In Children With Spastic Diplegia
NCT01367340	Not specified	UNKNOWN	Effect of Physical Activity Intervention Children With Spastic Diplegia After Resistance Training
NCT02988557	Not specified	COMPLETED	Walking Inclined Plane
NCT03166293	Not specified	COMPLETED	Early Intensive Exercise to Improve Walking in Children With Spastic Diplegia
NCT04792229	Not specified	COMPLETED	Effects Of Whole Body Vibration On Lower Extremity With Diplegic Spastic Cerebral Palsy
NCT04839939	Not specified	COMPLETED	Efficacy of Combination Taping Technique vs Ankle Foot Orthosis on Improving Gait Parameters in Cerebral Palsy
NCT05014451	Not specified	UNKNOWN	Pelvic Alignment in Relation to Standing Balance and Selective Motor Control in Children With Spastic Diplegia
NCT05032703	Not specified	COMPLETED	Arm Ergometer Versus Stabilization Exercises on Trunk Control and Upper Extremity Functions in cp
NCT05294874	Not specified	COMPLETED	Gait Rehabilitation in Diplegic Children
NCT06822296	Not specified	COMPLETED	Effect of Core Stability Training on Segmental Trunk Control and Quality of Life in Children with Cerebral Palsy