Down syndrome

Summary

Down syndrome (MONDO:0008608) is a disease with 5 cohort genes and 360 clinical trials. Top therapeutic interventions include mercaptopurine anhydrous, rivastigmine, and memantine.

At a glance

• Prevalence: 1-5 / 10 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 5
• ClinVar variants: 11
• Phenotypes (HPO): 72
• Clinical trials: 360

Clinical features

Epidemiology

Prevalence records

24 prevalence record(s), Orphanet, top 20 (validated / broadest geography first):

Type	Class	Value	Geography	Validation
Point prevalence	1-5 / 10 000		Worldwide	Validated
Prevalence at birth	6-9 / 10 000	95	Worldwide	Validated
Point prevalence	1-5 / 10 000	57	Europe	Validated
Prevalence at birth	>1 / 1000	101	Europe	Validated
Point prevalence	6-9 / 10 000	66	United Kingdom	Validated
Prevalence at birth	6-9 / 10 000	63.7	France	Validated
Prevalence at birth	6-9 / 10 000	98.3	Germany	Validated
Prevalence at birth	6-9 / 10 000	70	Belgium	Validated
Prevalence at birth	6-9 / 10 000	74	Italy	Validated
Prevalence at birth	6-9 / 10 000	91.2	Netherlands	Validated
Prevalence at birth	>1 / 1000	110	Norway	Validated
Prevalence at birth	6-9 / 10 000	69	Spain	Validated
Prevalence at birth	1-5 / 10 000	38	Portugal	Validated
Prevalence at birth	6-9 / 10 000	91.6	United Kingdom	Validated
Prevalence at birth	6-9 / 10 000	98	Switzerland	Validated
Prevalence at birth	6-9 / 10 000	66	Poland	Validated
Prevalence at birth	1-5 / 10 000	59	Denmark	Validated
Prevalence at birth	1-5 / 10 000	44	Croatia	Validated
Prevalence at birth	6-9 / 10 000	75	Hungary	Validated
Prevalence at birth	>1 / 1000	235	Ireland	Validated

Signs & symptoms

Clinical features (HPO)

72 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0000248	Brachycephaly	Very frequent (80-99%)
HP:0000286	Epicanthus	Very frequent (80-99%)
HP:0000470	Short neck	Very frequent (80-99%)
HP:0000474	Thickened nuchal skin fold	Very frequent (80-99%)
HP:0000582	Upslanted palpebral fissure	Very frequent (80-99%)
HP:0001156	Brachydactyly	Very frequent (80-99%)
HP:0001249	Intellectual disability	Very frequent (80-99%)
HP:0001252	Hypotonia	Very frequent (80-99%)
HP:0001328	Specific learning disability	Very frequent (80-99%)
HP:0001382	Joint hypermobility	Very frequent (80-99%)
HP:0005280	Depressed nasal bridge	Very frequent (80-99%)
HP:0011897	Neutrophilia	Very frequent (80-99%)
HP:0012368	Flat face	Very frequent (80-99%)
HP:0100830	Round ear	Very frequent (80-99%)
HP:0000144	Decreased fertility	Frequent (30-79%)
HP:0000158	Macroglossia	Frequent (30-79%)
HP:0000160	Narrow mouth	Frequent (30-79%)
HP:0000164	Abnormality of the dentition	Frequent (30-79%)
HP:0000179	Thick lower lip vermilion	Frequent (30-79%)
HP:0000189	Narrow palate	Frequent (30-79%)
HP:0000194	Open mouth	Frequent (30-79%)
HP:0000235	Abnormality of the fontanelles or cranial sutures	Frequent (30-79%)
HP:0000457	Depressed nasal ridge	Frequent (30-79%)
HP:0000475	Broad neck	Frequent (30-79%)
HP:0000691	Microdontia	Frequent (30-79%)
HP:0001513	Obesity	Frequent (30-79%)
HP:0001537	Umbilical hernia	Frequent (30-79%)
HP:0001629	Ventricular septal defect	Frequent (30-79%)
HP:0001852	Sandal gap	Frequent (30-79%)
HP:0001871	Abnormality of blood and blood-forming tissues	Frequent (30-79%)
HP:0001873	Thrombocytopenia	Frequent (30-79%)
HP:0001901	Polycythemia	Frequent (30-79%)
HP:0002247	Duodenal atresia	Frequent (30-79%)
HP:0002376	Developmental regression	Frequent (30-79%)
HP:0002511	Alzheimer disease	Frequent (30-79%)
HP:0002714	Downturned corners of mouth	Frequent (30-79%)
HP:0003196	Short nose	Frequent (30-79%)
HP:0004209	Clinodactyly of the 5th finger	Frequent (30-79%)
HP:0004322	Short stature	Frequent (30-79%)
HP:0006695	Atrioventricular canal defect	Frequent (30-79%)
HP:0007495	Prematurely aged appearance	Frequent (30-79%)
HP:0007598	Bilateral single transverse palmar creases	Frequent (30-79%)
HP:0010808	Protruding tongue	Frequent (30-79%)
HP:0010978	Abnormality of immune system physiology	Frequent (30-79%)
HP:0030680	Abnormal cardiovascular system morphology	Frequent (30-79%)
HP:0100763	Abnormality of the lymphatic system	Frequent (30-79%)
HP:0000405	Conductive hearing impairment	Occasional (5-29%)
HP:0000486	Strabismus	Occasional (5-29%)
HP:0000498	Blepharitis	Occasional (5-29%)
HP:0000518	Cataract	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Down syndrome
Mondo ID	MONDO:0008608
EFO	EFO:0001064
MeSH	D004314
OMIM	190685
Orphanet	870
DOID	DOID:14250
ICD-10-CM	Q90
ICD-11	1624623908
NCIT	C2993
SNOMED CT	41040004
UMLS	C0013080
MedGen	4385
MedDRA	10044688
Is cancer (heuristic)	no

Also known as: complete trisomy 21 syndrome · Down syndrome · Down syndrome, Isolated cases · Down’s syndrome · leukemia, megakaryoblastic, with or without Down syndrome, somatic · trisomy 21 · trisomy 21 (Down syndrome) · trisomy 21 syndrome

Data availability: 11 ClinVar variants · 231 cell lines.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › chromosomal disorder › autosomal anomaly › chromosome 21 disorder › Down syndrome

Related subtypes (5): ring chromosome 21, monosomy 21, tetrasomy 21, maternal uniparental disomy of chromosome 21, paternal uniparental disomy of chromosome 21

Subtypes (3): trisomy 21, translocation Down syndrome, partial segmental duplication

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

11 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 2 pathogenic, 2 benign/likely benign, 2 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic, 1 risk factor

ClinVar	Variant (HGVS)	Gene	Classification	Review
1705932	GRCh37/hg19 21q11.2-22.3(chr21:14420615-48080926)x3	ABCG1	Pathogenic	no assertion criteria provided
1068556	NM_002049.4(GATA1):c.231_232dup (p.Tyr78fs)	GATA1	Pathogenic	criteria provided, multiple submitters, no conflicts
952388	NM_002049.4(GATA1):c.35C>G (p.Ser12Ter)	GATA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
984916	NC_000004.12:g.1113690T>C	RNF212	risk factor	no assertion criteria provided
907893	NM_080680.3(COL11A2):c.3706C>T (p.Arg1236Cys)	COL11A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
465135	NM_002049.4(GATA1):c.94G>A (p.Val32Ile)	GATA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
550971	NM_001378454.1(ALMS1):c.8240T>G (p.Val2747Gly)	ALMS1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1429222	NM_002049.4(GATA1):c.893G>A (p.Arg298Gln)	GATA1	Uncertain significance	criteria provided, multiple submitters, no conflicts
945514	NM_002049.4(GATA1):c.944A>G (p.Lys315Arg)	GATA1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1563494	NM_002049.4(GATA1):c.599-9C>T	GATA1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
258542	NM_002049.4(GATA1):c.174G>A (p.Ala58=)	GATA1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 15 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COL11A2	Orphanet:1427	Autosomal recessive otospondylomegaepiphyseal dysplasia
COL11A2	Orphanet:166100	Autosomal dominant otospondylomegaepiphyseal dysplasia
COL11A2	Orphanet:2021	Fibrochondrogenesis
COL11A2	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
COL11A2	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB
RNF212	Orphanet:399805	Male infertility with azoospermia or oligozoospermia due to single gene mutation
GATA1	Orphanet:124	Diamond-Blackfan anemia
GATA1	Orphanet:231393	Beta-thalassemia-X-linked thrombocytopenia syndrome
GATA1	Orphanet:363727	X-linked dyserythropoietic anemia with abnormal platelets and neutropenia
GATA1	Orphanet:420611	Transient myeloproliferative syndrome
GATA1	Orphanet:67044	Thrombocytopenia with congenital dyserythropoietic anemia
GATA1	Orphanet:79277	Congenital erythropoietic porphyria
GATA1	Orphanet:86849	Acute basophilic leukemia
GATA1	Orphanet:99887	Acute megakaryoblastic leukemia in children with Down syndrome
ALMS1	Orphanet:64	Alström syndrome

Cohort genes → proteins

5 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
COL11A2	HGNC:2187	ENSG00000204248	P13942	Collagen alpha-2(XI) chain	clinvar
RNF212	HGNC:27729	ENSG00000178222	Q495C1	Probable E3 SUMO-protein ligase RNF212	clinvar
GATA1	HGNC:4170	ENSG00000102145	P15976	Erythroid transcription factor	clinvar
ALMS1	HGNC:428	ENSG00000116127	Q8TCU4	Centrosome-associated protein ALMS1	clinvar
ABCG1	HGNC:73	ENSG00000160179	P45844	ATP-binding cassette sub-family G member 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COL11A2	Collagen alpha-2(XI) chain	May play an important role in fibrillogenesis by controlling lateral growth of collagen II fibrils.
RNF212	Probable E3 SUMO-protein ligase RNF212	SUMO E3 ligase that acts as a regulator of crossing-over during meiosis: required to couple chromosome synapsis to the formation of crossover-specific recombination complexes.
GATA1	Erythroid transcription factor	Transcriptional activator or repressor which serves as a general switch factor for erythroid development.
ALMS1	Centrosome-associated protein ALMS1	Involved in PCM1-dependent intracellular transport.
ABCG1	ATP-binding cassette sub-family G member 1	Catalyzes the efflux of phospholipids such as sphingomyelin, cholesterol and its oxygenated derivatives like 7beta-hydroxycholesterol and this transport is coupled to hydrolysis of ATP.

Protein-family classification

Druggable: 1 · Difficult: 2 · Unknown: 2 · Druggable fraction: 0.2

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
Transporter	1	15.6×	0.171
Transcription factor	2	3.3×	0.171
Other/Unknown	2	0.7×	0.877

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
COL11A2	Other/Unknown	no		Fib_collagen_C, Laminin_G, Collagen
RNF212	Transcription factor	no		Znf_RING, Znf_RING_CS, Zip3/RNF212-like
GATA1	Transcription factor	no		Znf_GATA, Znf_NHR/GATA, Transcription_factor_GATA
ALMS1	Other/Unknown	no		ALMS_motif, ALMS_repeat
ABCG1	Transporter	yes		ABC_transporter-like_ATP-bd, AAA+_ATPase, Pigment_permease/Abcg

Expression context

Cohort genes with no expression data: 0.

4 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)	5
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adenohypophysis	1
male germ line stem cell (sensu Vertebrata) in testis	1
pituitary gland	1
body of pancreas	1
cerebellar hemisphere	1
left ovary	1
blood	1
bone marrow	1
trabecular bone tissue	1
buccal mucosa cell	1
cardia of stomach	1
periodontal ligament	1
left adrenal gland	1
right adrenal gland	1
right adrenal gland cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COL11A2	134	broad	yes	pituitary gland, male germ line stem cell (sensu Vertebrata) in testis, adenohypophysis
RNF212	164	broad	marker	body of pancreas, cerebellar hemisphere, left ovary
GATA1	138	tissue_specific	marker	trabecular bone tissue, blood, bone marrow
ALMS1	275	ubiquitous	marker	buccal mucosa cell, periodontal ligament, cardia of stomach
ABCG1	270	ubiquitous	marker	right adrenal gland, left adrenal gland, right adrenal gland cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GATA1	4,810
ALMS1	2,976
ABCG1	2,178
COL11A2	1,583
RNF212	504

Structural data

PDB: 2 · AlphaFold-only: 3 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ABCG1	P45844	5
GATA1	P15976	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
RNF212	Q495C1	63.72
COL11A2	P13942	50.18
ALMS1	Q8TCU4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 36. Enrichment computed across 5 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
HDL remodeling	1	285.5×	0.050	ABCG1
ABC transporters in lipid homeostasis	1	150.3×	0.050	ABCG1
Plasma lipoprotein remodeling	1	119.0×	0.050	ABCG1
NR1H2 and NR1H3-mediated signaling	1	98.5×	0.050	ABCG1
MET activates PTK2 signaling	1	95.2×	0.050	COL11A2
NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux	1	77.2×	0.050	ABCG1
Collagen chain trimerization	1	64.9×	0.050	COL11A2
Centrosome maturation	1	63.4×	0.050	ALMS1
Plasma lipoprotein assembly, remodeling, and clearance	1	57.1×	0.050	ABCG1
Developmental Lineage of Pancreatic Ductal Cells	1	57.1×	0.050	COL11A2
Assembly of collagen fibrils and other multimeric structures	1	50.1×	0.050	COL11A2
Collagen degradation	1	43.9×	0.050	COL11A2
Collagen biosynthesis and modifying enzymes	1	42.6×	0.050	COL11A2
Loss of Nlp from mitotic centrosomes	1	39.6×	0.050	ALMS1
Loss of proteins required for interphase microtubule organization from the centrosome	1	39.6×	0.050	ALMS1
Non-integrin membrane-ECM interactions	1	38.6×	0.050	COL11A2
AURKA Activation by TPX2	1	38.1×	0.050	ALMS1
Recruitment of mitotic centrosome proteins and complexes	1	34.0×	0.050	ALMS1
Regulation of PLK1 Activity at G2/M Transition	1	31.7×	0.050	ALMS1
Mitotic G2-G2/M phases	1	31.7×	0.050	ALMS1
G2/M Transition	1	31.7×	0.050	ALMS1
ABC-family protein mediated transport	1	30.4×	0.050	ABCG1
RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function	1	30.1×	0.050	GATA1
Recruitment of NuMA to mitotic centrosomes	1	29.1×	0.050	ALMS1
Anchoring of the basal body to the plasma membrane	1	28.3×	0.050	ALMS1
Cilium Assembly	1	27.2×	0.050	ALMS1
Signaling by Nuclear Receptors	1	25.5×	0.052	ABCG1
RUNX1 regulates transcription of genes involved in differentiation of HSCs	1	23.8×	0.053	GATA1
Mitotic Prometaphase	1	17.3×	0.067	ALMS1
Factors involved in megakaryocyte development and platelet production	1	16.6×	0.067	GATA1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of primitive erythrocyte differentiation	1	1685.2×	0.009	GATA1
basophil differentiation	1	1685.2×	0.009	GATA1
eosinophil fate commitment	1	1685.2×	0.009	GATA1
meiotic gene conversion	1	1123.5×	0.009	RNF212
regulation of definitive erythrocyte differentiation	1	1123.5×	0.009	GATA1
glycoprotein transport	1	1123.5×	0.009	ABCG1
cellular response to high density lipoprotein particle stimulus	1	1123.5×	0.009	ABCG1
regulation of glycoprotein biosynthetic process	1	842.6×	0.009	GATA1
eosinophil differentiation	1	842.6×	0.009	GATA1
primitive erythrocyte differentiation	1	842.6×	0.009	GATA1
soft palate development	1	674.1×	0.010	COL11A2
response to lipid	1	481.5×	0.011	ABCG1
myeloid cell apoptotic process	1	421.3×	0.011	GATA1
negative regulation of myeloid cell apoptotic process	1	374.5×	0.011	GATA1
chiasma assembly	1	374.5×	0.011	RNF212
regulation of centriole replication	1	337.0×	0.011	ALMS1
negative regulation of cholesterol storage	1	306.4×	0.011	ABCG1
positive regulation of mast cell degranulation	1	306.4×	0.011	GATA1
osteoblast proliferation	1	280.9×	0.011	GATA1
cellular response to follicle-stimulating hormone stimulus	1	280.9×	0.011	GATA1
negative regulation of macrophage derived foam cell differentiation	1	259.3×	0.011	ABCG1
intracellular cholesterol transport	1	259.3×	0.011	ABCG1
megakaryocyte differentiation	1	240.7×	0.011	GATA1
positive regulation of osteoblast proliferation	1	240.7×	0.011	GATA1
amyloid precursor protein catabolic process	1	240.7×	0.011	ABCG1
phospholipid efflux	1	224.7×	0.011	ABCG1
positive regulation of cholesterol biosynthetic process	1	224.7×	0.011	ABCG1
Sertoli cell development	1	224.7×	0.011	GATA1
regulation of cholesterol metabolic process	1	224.7×	0.011	ABCG1
xenobiotic detoxification by transmembrane export across the plasma membrane	1	224.7×	0.011	ABCG1

Therapeutics

Drugs indicated for this disease

0 approved, 2 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Dextrothyroxine	Phase 3 (in late-stage trials)
Thyroid	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Bumetanide, Epigalocatechin Gallate, Human Immunoglobulin G, Lorazepam, Sargramostim, Tofacitinib.

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 5

Druggability breadth: 1 of 5 evidence-associated genes (20%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
COL11A2	0	0
RNF212	0	0
GATA1	0	0
ALMS1	0	0
ABCG1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; 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	ABCG1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	4	COL11A2, RNF212, GATA1, ALMS1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
COL11A2	0	—
RNF212	0	—
GATA1	0	—
ALMS1	0	—
ABCG1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 360.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	295
PHASE2	29
PHASE3	15
PHASE1	10
PHASE4	6
PHASE1/PHASE2	3
PHASE2/PHASE3	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04219280	PHASE4	RECRUITING	Evaluating Treatment of ADHD in Children with Down Syndrome
NCT06911944	PHASE4	NOT_YET_RECRUITING	Amyloid Lowering for Alzheimer’s in Down’s With Donanemab Investigation
NCT07280468	PHASE4	RECRUITING	Endotype DIrected Treatment for OSA in Down Syndrome
NCT01112683	PHASE4	COMPLETED	Efficacy and Safety of Memantine Hydrochloride in Enhancing the Cognitive Abilities of Young Adults With Down Syndrome
NCT04747275	PHASE4	TERMINATED	Use of Liquid Stable Levothyroxine in Trisomy 21 Pediatric Patients
NCT05458479	PHASE4	COMPLETED	Fluoxetine Treatment of Depression in Down Syndrome
NCT02521493	PHASE3	ACTIVE_NOT_RECRUITING	Response-Based Chemotherapy in Treating Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome in Younger Patients With Down Syndrome
NCT03914625	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Investigate Blinatumomab in Combination With Chemotherapy in Patients With Newly Diagnosed B-Lymphoblastic Leukemia
NCT04390646	PHASE2/PHASE3	RECRUITING	GnRH Therapy on Cognition in Down Syndrome
NCT04801771	PHASE3	ACTIVE_NOT_RECRUITING	Effects of Hypoglossal Nerve Stimulation on Cognition and Language in Down Syndrome and Obstructive Sleep Apnea
NCT07135167	PHASE3	RECRUITING	Compassionate Use Study of Epi-ON Corneal Collagen Crosslinking Performed Using UVA Exposure on Eyes With Ectatic Corneal Diseases for Subjects With Down Syndrome
NCT07232134	PHASE3	RECRUITING	The Efficacy of Therapy in Patients With Acute Myeloid Leukemia and Down Syndrome in Russia
NCT07234695	PHASE3	RECRUITING	LEvetiracetam to Prevent Seizures in Symptomatic Alzheimer’s Disease in Adults With Down Syndrome
NCT07238465	PHASE3	RECRUITING	Exploring Sympathetic Nervous System Function in Individuals With Down Syndrome
NCT00056329	PHASE3	UNKNOWN	Vitamin E in Aging Persons With Down Syndrome
NCT00294593	PHASE2/PHASE3	COMPLETED	Efficacy Study of Folinic Acid to Improve Mental Development of Children With Down Syndrome
NCT00754013	PHASE3	TERMINATED	Evaluating The Efficacy And Safety Of Donepezil Hydrochloride (Aricept) In The Treatment Of The Cognitive Dysfunction Exhibited By Children With Down Syndrome, Aged 6 To 10
NCT00754052	PHASE3	TERMINATED	Evaluating The Efficacy And Safety Of Donepezil Hydrochloride (Aricept) In The Treatment Of The Cognitive Dysfunction Exhibited By Children With Down Syndrome, Aged 11 To 17
NCT01190930	PHASE3	COMPLETED	Risk-Adapted Chemotherapy in Treating Younger Patients With Newly Diagnosed Standard-Risk Acute Lymphoblastic Leukemia or Localized B-Lineage Lymphoblastic Lymphoma
NCT01576705	PHASE3	COMPLETED	Efficacy Assessment of Systematic Treatment With Folinic Acid and Thyroid Hormone on Psychomotor Development of Down Syndrome Young Children
NCT01594346	PHASE3	COMPLETED	Multicenter Vitamin E Trial in Aging Persons With Down Syndrome
NCT05528549	PHASE3	COMPLETED	Blood Flow and Blood Pressure Investigation in Down Syndrome
NCT06860373	PHASE3	TERMINATED	LIFE-DSR-Biomarker Sub-study of Biomarkers in Down Syndrome Related Alzheimer’s Disease (DS-AD)
NCT03286634	PHASE2	ACTIVE_NOT_RECRUITING	ASIA Down Syndrome Acute Lymphoblastic Leukemia 2016
NCT04546399	PHASE2	RECRUITING	A Study to Compare Blinatumomab Alone to Blinatumomab With Nivolumab in Patients Diagnosed With First Relapse B-Cell Acute Lymphoblastic Leukemia (B-ALL)
NCT05231798	PHASE2	RECRUITING	Cholinergic Integrity in Down Syndrome in Association With Aging, Alzheimer’s Disease Pathology, and Cognition
NCT05662228	PHASE2	ACTIVE_NOT_RECRUITING	Therapies for Down Syndrome Regression Disorder
NCT05933603	PHASE2	ACTIVE_NOT_RECRUITING	Medications for Obstructive Sleep Apnea to Improve Cognition in Children With Down Syndrome
NCT06043440	PHASE2	RECRUITING	Down Syndrome Obstructive Sleep Apnea
NCT06465823	PHASE2	RECRUITING	Efficacy of Bumetanide to Improve Cognitive Functions in Down Syndrome
NCT07334912	PHASE2	RECRUITING	AEF0217 in Participants With Down Syndrome
NCT07598643	PHASE2	RECRUITING	Modulation of the Immune System in Down Syndrome for Improved Outcomes and Neurodevelopment - 1
NCT00570128	PHASE2	COMPLETED	Evaluating The Efficacy And Safety Of Donepezil Hydrochloride (HCl) (Aricept) In Treating Cognitive Dysfunction Exhibited By Children With Down Syndrome
NCT00675025	PHASE2	TERMINATED	Evaluating The Safety Of Donepezil Hydrochloride (Aricept) For Up To 1 Year In The Treatment Of The Cognitive Dysfunction Exhibited By Children With Down Syndrome - Follow-Up To A 10-Week, Double-Blind, Placebo-Controlled Trial
NCT00891917	PHASE2	WITHDRAWN	Liq-NOL Efficacy in Pediatric Patients With Down Syndrome
NCT00928304	PHASE2	COMPLETED	Phase II Study of Florbetaben (BAY94-9172) PET Imaging for Detection/Exclusion of Cerebral β-amyloid.
NCT01084135	PHASE1/PHASE2	COMPLETED	Rivastigmine Study in Adolescents With Down Syndrome
NCT01394796	PHASE2	COMPLETED	Egcg, a dyrk1a Inhibitor as Therapeutic Tool for Reversing Cognitive Deficits in Down Syndrome Individuals.
NCT01699711	PHASE2	COMPLETED	Normalization of dyrk1A and APP Function as an Approach to Improve Cognitive Performance and Decelerate AD Progression in DS Subjects: Epigallocatechin Gallate as Therapeutic Tool
NCT01778946	PHASE1/PHASE2	COMPLETED	Nicotine Treatment of Cognitive Decline in Down Syndrome

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
MERCAPTOPURINE ANHYDROUS	4	6
RIVASTIGMINE	4	6
MEMANTINE	4	5
ATOMOXETINE	4	4
DAUNORUBICIN	4	3
DONEPEZIL	4	3
FLORBETAPIR	4	3
FLUOXETINE	4	3
PEGASPARGASE	4	3
THIOGUANINE	4	3
TOFACITINIB CITRATE	4	3
ASPARAGINASE	4	2
ASPARAGINASE ERWINIA CHRYSANTHEMI	4	2
BLINATUMOMAB	4	2
GONADORELIN	4	2
VITAMIN E	4	2
BUMETANIDE	4	1
CAFFEINE	4	1
CALASPARGASE PEGOL	4	1
DESFLURANE	4	1
DONANEMAB	4	1
FLORBETABEN	4	1
FLUDEOXYGLUCOSE	4	1
HYDROCORTISONE SODIUM SUCCINATE	4	1
IDARUBICIN	4	1
INSULIN GLULISINE	4	1
LEVETIRACETAM	4	1
LEVOTHYROXINE	4	1
LORAZEPAM	4	1
METHYLPHENIDATE HYDROCHLORIDE	4	1