ocular motor apraxia, Cogan type

Summary

ocular motor apraxia, Cogan type (MONDO:0009764) is a disease caused by SUFU (GenCC Strong), with 1 cohort gene and 70 clinical trials. Top therapeutic interventions include amantadine, baclofen, and fosphenytoin.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: SUFU (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 15
• Clinical trials: 70

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		50	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

15 HPO clinical features (Orphanet curated; top 15 by frequency):

HPO ID	Term	Frequency
HP:0000657	Oculomotor apraxia	Very frequent (80-99%)
HP:0001251	Ataxia	Very frequent (80-99%)
HP:0000750	Delayed speech and language development	Frequent (30-79%)
HP:0001151	Impaired horizontal smooth pursuit	Frequent (30-79%)
HP:0001270	Motor delay	Frequent (30-79%)
HP:0001328	Specific learning disability	Frequent (30-79%)
HP:0002419	Molar tooth sign on MRI	Frequent (30-79%)
HP:0006817	Aplasia/Hypoplasia of the cerebellar vermis	Frequent (30-79%)
HP:0006961	Jerky head movements	Frequent (30-79%)
HP:0000486	Strabismus	Occasional (5-29%)
HP:0000639	Nystagmus	Occasional (5-29%)
HP:0001249	Intellectual disability	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001252	Hypotonia	Occasional (5-29%)
HP:0002312	Clumsiness	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	ocular motor apraxia, Cogan type
Mondo ID	MONDO:0009764
MeSH	C537423
OMIM	257550
Orphanet	1125
DOID	DOID:0080849
SNOMED CT	405809000
UMLS	C0543874
MedGen	154254
GARD	0000016
NORD	1517
Is cancer (heuristic)	no

Also known as: Cogan’s syndrome type 2 · COMA · congenital oculomotor apraxia · oculomotor apraxia Cogan type · oculomotor apraxia, Cogan type · oculomotor apraxia, congenital, Cogan-type · saccade initiation failure congenital

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

Disease family

Classification path: disease › human disease › disease by body system or component › disorder of orbital region › eye disorder › ocular motor apraxia, Cogan type

Related subtypes (119): ptosis, eye accommodation disease, corneal disorder, asthenopia, lens disorder, keratomalacia, scleral disorder, ocular siderosis, coloboma, luxation of globe, mucopolysaccharidosis type 1, lacrimal apparatus disorder, Foster-Kennedy syndrome, anterior dislocation of lens, uveal disorder, eyelid disorder, ocular hypotension, scotoma, exophthalmos, ophthalmia nodosa, eye degenerative disorder, refractive error, glaucoma, retinal disorder, eye allergy, ocular vascular disorder, optic neuritis, conjunctival disorder, ocular hypertension, Tietz syndrome, Alagille syndrome, glaucoma-sleep apnea syndrome, Marshall syndrome, microcornea-glaucoma-absent frontal sinuses syndrome, nail-patella syndrome, oculodentodigital dysplasia, piebaldism, Sturge-Weber syndrome, cerebrotendinous xanthomatosis, ocular cystinosis, alpha-mannosidosis, megalocornea-intellectual disability syndrome, mucolipidosis type IV, mucopolysaccharidosis type 6, Netherton syndrome, galactosialidosis, Niemann-Pick disease type A, Peters plus syndrome, isolated Pierre-Robin syndrome, ectodermal dysplasia-blindness syndrome, Sandhoff disease, SHORT syndrome, Sjogren-Larsson syndrome, Smith-Lemli-Opitz syndrome, Tay-Sachs disease, tyrosinemia type II, Ito hypomelanosis, X-linked cone dysfunction syndrome with myopia, red color blindness, oculocerebrorenal syndrome, Lowry-MacLean syndrome, pigment dispersion syndrome, hereditary hyperferritinemia with congenital cataracts, dyssegmental dysplasia-glaucoma syndrome, mevalonic aciduria, familial cavitary optic disk anomaly, blindness - scoliosis - arachnodactyly syndrome, fatty acyl-CoA reductase 1 deficiency, microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome, neurotrophic keratopathy, Cogan syndrome, atopic keratoconjunctivitis, rhizomelic chondrodysplasia punctata, Ehlers-Danlos syndrome, kyphoscoliotic type 1, IRVAN syndrome, Rothmund-Thomson syndrome type 2, microcornea-corectopia-macular hypoplasia syndrome, isolated anophthalmia-microphthalmia syndrome, Spasmus nutans, toxic maculopathy due to antimalarial drugs, syndromic recessive X-linked ichthyosis, acute zonal occult outer retinopathy, acute annular outer retinopathy, phakomatosis pigmentovascularis, lamellar ichthyosis, idiopathic linear interstitial keratitis, chondroectodermal dysplasia with night blindness, galactosemia, GM1 gangliosidosis, Gaucher disease, visual snow syndrome, extensive peripapillary myelinated nerve fibers, IgG4-related ophthalmic disorder, global developmental delay-visual anomalies-progressive cerebellar atrophy-truncal hypotonia syndrome, vernal keratoconjunctivitis, Gardner syndrome, anterior segment dysgenesis, isolated ankyloblepharon filiforme adnatum, hereditary optic neuropathy, essential strabismus, Axenfeld anomaly, eye neoplasm, isolated blepharochalasis, punctate inner choroidopathy, eye infectious disorder, vitreous body disorder, 9q33.3q34.11 microdeletion syndrome, autoimmune/inflammatory optic neuropathy, LTBP2-related ocular dysgenesis, ocular growth disorder, ocular dysgenesis caused by defects in PAX6 regulation, choroidal neovascularization, anterior segment developmental abnormality with extraocular manifestations, congenital optic disk excavation, neuroocular syndrome, isolated angioid streaks, multiple evanescent white dot syndrome, stellate multiform amelanotic choroidopathy, macular telangiectasia

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 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
3376559	NM_016169.4(SUFU):c.596A>G (p.Gln199Arg)	SUFU	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 16 · Orphanet: 7 · 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
SUFU	Strong	Autosomal dominant	ocular motor apraxia, Cogan type	16

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SUFU	Orphanet:2495	Meningioma
SUFU	Orphanet:251858	Medulloblastoma with extensive nodularity
SUFU	Orphanet:251863	Desmoplastic/nodular medulloblastoma
SUFU	Orphanet:263662	Familial multiple meningioma
SUFU	Orphanet:280200	Microform holoprosencephaly
SUFU	Orphanet:377	Gorlin syndrome
SUFU	Orphanet:475	Isolated Joubert syndrome

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
SUFU	HGNC:16466	ENSG00000107882	Q9UMX1	Suppressor of fused homolog	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SUFU	Suppressor of fused homolog	Negative regulator in the hedgehog/smoothened signaling pathway.

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)
SUFU	Other/Unknown	no		Suppressor_of_fused, Suppressor_of_fused_euk, SUFU-like_domain

Expression context

Cohort genes with no expression data: 0.

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
kidney epithelium	1
upper arm skin	1
vena cava	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SUFU	226	ubiquitous	yes	upper arm skin, kidney epithelium, vena cava

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SUFU	2,188

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SUFU	Q9UMX1	10

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. 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
Degradation of GLI1 by the proteasome	1	223.9×	0.007	SUFU
Degradation of GLI2 by the proteasome	1	223.9×	0.007	SUFU
GLI3 is processed to GLI3R by the proteasome	1	223.9×	0.007	SUFU
Signaling by Hedgehog	1	184.2×	0.007	SUFU
Hedgehog ‘off’ state	1	178.4×	0.007	SUFU
Hedgehog ‘on’ state	1	158.6×	0.007	SUFU
Signal Transduction	1	10.2×	0.098	SUFU

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
positive regulation of cellular response to drug	1	16852.0×	6e-04	SUFU
smoothened signaling pathway involved in ventral spinal cord interneuron specification	1	8426.0×	6e-04	SUFU
smoothened signaling pathway involved in spinal cord motor neuron cell fate specification	1	8426.0×	6e-04	SUFU
maintenance of protein localization in organelle	1	8426.0×	6e-04	SUFU
negative regulation of protein import into nucleus	1	936.2×	0.003	SUFU
negative regulation of ubiquitin-dependent protein catabolic process	1	842.6×	0.003	SUFU
dorsal/ventral neural tube patterning	1	802.5×	0.003	SUFU
coronary vasculature development	1	624.1×	0.004	SUFU
aorta development	1	561.7×	0.004	SUFU
ventricular septum development	1	495.6×	0.004	SUFU
negative regulation of smoothened signaling pathway	1	455.5×	0.004	SUFU
skin development	1	443.5×	0.004	SUFU
negative regulation of osteoblast differentiation	1	295.6×	0.005	SUFU
heart looping	1	267.5×	0.005	SUFU
neural tube closure	1	187.2×	0.007	SUFU
spermatid development	1	145.3×	0.008	SUFU
regulation of DNA-templated transcription	1	31.6×	0.035	SUFU
negative regulation of transcription by RNA polymerase II	1	17.7×	0.060	SUFU
signal transduction	1	16.1×	0.062	SUFU

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
SUFU	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SUFU	1	Binding:1

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	SUFU

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)
SUFU	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 70.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	58
PHASE2	6
PHASE4	3
PHASE1	2
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00644722	PHASE4	COMPLETED	Out-of-Hospital Intubation With Metal Single Use Laryngoscope Blades
NCT02130674	PHASE4	COMPLETED	Optimized Therapy in Severe Traumatic Brain Injured Patients
NCT06081283	PHASE4	TERMINATED	Antiseizure Medication in Seizure Networks at Early Acute Brain Injury
NCT02000674	PHASE3	COMPLETED	Succinylcholine vs Rocuronium for Prehospital Emergency Intubation
NCT00221689	PHASE2	TERMINATED	Intrathecal Baclofen Therapy and Paroxysmal Dysautonomia in Severe Brain-Injured Patients
NCT00593164	PHASE2	WITHDRAWN	Clinical Study of the LRS ThermoSuit™ System in Post Arrest Patients With Intravenous Infusion of Magnesium Sulfate
NCT02486211	PHASE2	COMPLETED	Amantadine to Speed Awakening After Cardiac Arrest
NCT03399318	PHASE2	COMPLETED	Aggressive Antipyretics for Fever Reduction in CNS Malaria
NCT04219735	PHASE2	COMPLETED	Effect of Minocycline on Delirium Incidence in Critically Ill Patients
NCT04772547	PHASE2	COMPLETED	VIGABatrin in Post-anoxic STATus Epilepticus - Phase IIa
NCT03814356	PHASE1	ACTIVE_NOT_RECRUITING	Stimulant Therapy Targeted to Individualized Connectivity Maps to Promote ReACTivation of Consciousness
NCT00410969	PHASE1	COMPLETED	Pilot Clinical Study of the LRS ThermoSuit™ System in Post Arrest Patients
NCT01239420	Not specified	ACTIVE_NOT_RECRUITING	Norwegian Cardio-Respiratory Arrest Study
NCT03655561	Not specified	ACTIVE_NOT_RECRUITING	Lassa Fever Clinical Course and Prognostic Factors in Nigeria
NCT05321459	Not specified	RECRUITING	Predictive Outcome in Comatose Patients
NCT05861323	Not specified	ACTIVE_NOT_RECRUITING	Feasibility of the Comfort Measures Only Time Out (CMOT)
NCT05922644	Not specified	RECRUITING	Short-term Cervical Spinal Cord Stimulation in Patients With Disorders of Consciousness After Intracerebral Hemorrhage
NCT06265168	Not specified	ACTIVE_NOT_RECRUITING	Comprehensive Observations and Multidisciplinary Approaches in the Management of Unconscious Patients
NCT06549426	Not specified	RECRUITING	Treatment of ELectroencephalographic STatus Epilepticus After Cardiopulmonary Resuscitation-2 (TELSTAR-2)
NCT06564662	Not specified	RECRUITING	Rapid-Response EEG in Children With Suspected Status Epilepticus
NCT06617377	Not specified	NOT_YET_RECRUITING	Combined Whole-brain Structural and Functional MRI for the Prediction of Neurological Recovery After Cardiac Arrest
NCT06696690	Not specified	NOT_YET_RECRUITING	The Safety and Efficacy of Median Nerve Electrical Stimulation for Improving Neurological Function Prognosis in Patients With Cardiac Arrest
NCT07177755	Not specified	NOT_YET_RECRUITING	Assessment of Structural Brain Changes Related to Anoxic Coma Using High-field and Very Low Field Mobile MRI
NCT07247669	Not specified	RECRUITING	Evaluation and Optimization of Telephone Triage Using Artificial Intelligence (AI) Models for the Detection of Demands for Time-dependent Pathology at the Emergency and Urgent Care Coordination Center (CCUE).
NCT07331324	Not specified	NOT_YET_RECRUITING	The Coma Family Program (COMA-F): A Resilience Program for Caregivers of Patients With Severe Acute Brain Injury
NCT07485361	Not specified	NOT_YET_RECRUITING	fNIRS for Disorders of Consciousness
NCT07614074	Not specified	RECRUITING	Recovery Trajectory for Coma and Disorders of Consciousness
NCT00122707	Not specified	COMPLETED	Comparison of Central and Peripheral Venous Catheters
NCT00557076	Not specified	COMPLETED	The Efficacy of Familiar Voice Stimulation During Coma Recovery
NCT00573014	Not specified	COMPLETED	Cervical Spine Clearance in Obtunded Trauma Patients
NCT00577954	Not specified	COMPLETED	Multimodal Resonance Imaging for Outcome Prediction on Coma Patients
NCT00880204	Not specified	COMPLETED	Evaluation of Essential Surgical Skills-Emergency Maternal and Child Health Training
NCT00959829	Not specified	COMPLETED	Use of Music and Voice Stimulus on Coma Patients
NCT01620957	Not specified	COMPLETED	Longitudinal Study of the Default-mode Network Connectivity in Brain Injured Patients Recovering From Coma
NCT01897194	Not specified	COMPLETED	Using EEG to Study Coma in the Neurocritical Care Unit
NCT01973829	Not specified	COMPLETED	The Checklist for Early Recognition and Treatment of Acute Illness (CERTAIN)
NCT01973894	Not specified	COMPLETED	Midazolam Whole Body Physiologically Based Pharmacokinetic Model
NCT01980446	Not specified	COMPLETED	Cognitive Auditory Evoked Potential After Cardiac Arrest: Interest of Mismatch negativiTY
NCT02039297	Not specified	COMPLETED	Patient Centered Cloud-based Electronic System: Ambient Warning and Response Evaluation (ProCCESs AWARE)
NCT02329028	Not specified	COMPLETED	Feasibility of Mini-EEG in the Prehospital Setting

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
AMANTADINE	4	2
BACLOFEN	4	1
FOSPHENYTOIN	4	1
LEVETIRACETAM	4	1
PHENOBARBITAL	4	1
VALPROATE SODIUM	4	1
THYROID	3	1
ETIRACETAM	2	1
CHEMBL354261	0	1
LEVITIRACETAM	0	1