ORPHA:300570
Cortical dysgenesis with pontocerebellar hypoplasia due to TUBB3 mutation
- Type
- Disease
- Group
- Disorder
- Inheritance
- Autosomal dominant
- Age of onset
- Infancy, Neonatal
- Status
- active
A rare, genetic, non-syndromic cerebral malformation due to abnormal neuronal migration disease characterized by the association of cortical dysplasia and pontocerebellar hypoplasia, manifesting with global developmental delay, mild to severe intellectual disability, axial hypotonia, strabismus, nystagmus and, occasionally, optic nerve hypoplasia. Brain imaging reveals variable malformations, including frontally predominant microgyria, gyral disorganization and simplification, dysmorphic and hypertrophic basal ganglia, cerebellar vermis dysplasia, brainstem/corpus callosum hypoplasia, and/or olfactory bulbs agenesis.
1
Names in Orphadata languages
12 of 12 languages| Lang | Name | Synonyms |
|---|---|---|
| en | Cortical dysgenesis with pontocerebellar hypoplasia due to TUBB3 mutation | |
| fr | Dysgénésie corticale avec hypoplasie pontocérébelleuse due à une mutation TUBB3 | |
| de | Kortikale Dysgenese mit pontozerebellärer Hypoplasie durch TUBB3-Genmutation | |
| es | Disgenesia cortical con hipoplasia pontocerebelosa por una mutación en el gen TUBB3 | |
| it | Disgenesia corticale con ipoplasia pontocerebellare da mutazione in TUBB3 | |
| nl | Corticale dysgenesie met pontocerebellaire hypoplasie door TUBB3-mutatie | |
| pt | Disgenesia cortical com hipoplasia pontocerebelosa por mutação TUBB3 | |
| pl | Dysgenezja kory z hipoplazją mostu i móżdżku z powodu mutacji TUBB3 | |
| cs | Kortikální dysgeneze s pontocerebelární hypoplázií způsobená mutací v TUBB3 genu | |
| uk | Дисгенезія кори головного мозку з гіпоплазією мозочка, зумовлена мутацією TUBB3 | |
| zh | TUBB3基因变异所致皮质发育不全伴桥小脑发育不良 | |
| tr | TUBB3 mutasyonuna bağlı pontoserebellar hipoplazi ile seyreden kortikal disgenezi |
Definition in:
2
Cross-references
qualifier = Orphanet mapping relation| Source | Code | Qualifier | ICD relation | Validation |
|---|---|---|---|---|
| OMIM | 614039 | E | validated | |
| ICD-10 | Q04.3 | NTBT | attributed | validated |
| MONDO | 0013541 | E | validated | |
| UMLS | C5191309 | E | validated | |
| GARD | 13032 | E | validated |
E exact · NTBT this ORPHAcode is narrower than the target · BTNT broader than the target · ND not decided.
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Classification
Preferential parent (Orphanet linearisation):
Parents in the classifications (3):
- ORPHA:611327Genetic multiple congenital anomalies/dysmorphic syndrome-intellectual disability
rare genetic diseases - ORPHA:102283Multiple congenital anomalies/dysmorphic syndrome-intellectual disability
rare developmental anomalies during embryogenesis; rare neurological diseases - ORPHA:163209Non-syndromic cerebral malformation due to abnormal neuronal migration
rare developmental anomalies during embryogenesis; rare genetic diseases; rare neurological diseases
No children.
4
Genes
1 direct| Gene | Association | Status | HGNC | Ensembl | OMIM | Locus | Name | Source of validation |
|---|---|---|---|---|---|---|---|---|
| TUBB3 | Disease-causing germline mutation(s) in | Assessed | HGNC:20772 | ENSG00000258947 | 602661 | 16q24.3 | tubulin beta 3 class III | 20829227[PMID] |
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Prevalence and incidence
2 records| Type | Class | Value | Area | Qualification | Validation | Source |
|---|---|---|---|---|---|---|
| Cases/families | 12 cases | Worldwide | Case(s) | Validated | 20829227[PMID] | |
| Point prevalence | <1 / 1 000 000 | — | Worldwide | Class only | Validated | ORPHANET |
Value is Orphadata's ValMoy: the mean estimate per 100 000 for prevalence and incidence, the number of cases or families for case reports.
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HPO phenotypes
79 annotations · validated 2019-02-07| HPO | Term (as annotated by Orphanet) | Diagnostic |
|---|---|---|
| Obligate (100%) | ||
| HP:0001250 | Seizure | |
| Very frequent (99-80%) | ||
| HP:0001263 | Global developmental delay | |
| Frequent (79-30%) | ||
| HP:0000496 | Abnormality of eye movement | |
| HP:0002334 | Abnormality of the cerebellar vermis | |
| HP:0008936 | Axial hypotonia | |
| HP:0001488 | Bilateral ptosis | |
| HP:0001321 | Cerebellar hypoplasia | |
| HP:0025336 | Delayed ability to sit | |
| HP:0010862 | Delayed fine motor development | |
| HP:0002194 | Delayed gross motor development | |
| HP:0000565 | Esotropia | |
| HP:0002474 | Expressive language delay | |
| HP:0008872 | Feeding difficulties in infancy | |
| HP:0002365 | Hypoplasia of the brainstem | |
| HP:0002079 | Hypoplasia of the corpus callosum | |
| HP:0002540 | Inability to walk | |
| HP:0001249 | Intellectual disability | |
| HP:0001339 | Lissencephaly | |
| HP:0000639 | Nystagmus | |
| HP:0001338 | Partial agenesis of the corpus callosum | |
| HP:0002126 | Polymicrogyria | |
| HP:0002465 | Poor speech | |
| HP:0008897 | Postnatal growth retardation | |
| HP:0011344 | Severe global developmental delay | |
| HP:0009879 | Simplified gyral pattern | |
| HP:0002497 | Spastic ataxia | |
| HP:0001257 | Spasticity | |
| HP:0000486 | Strabismus | |
| HP:0007260 | Type II lissencephaly | |
| Occasional (29-5%) | ||
| HP:0012332 | Abnormal autonomic nervous system physiology | |
| HP:0002134 | Abnormal basal ganglia morphology | |
| HP:0030534 | Abnormal best corrected visual acuity test | |
| HP:0000733 | Abnormal repetitive mannerisms | |
| HP:0000570 | Abnormal saccadic eye movements | |
| HP:0010663 | Abnormality of thalamus morphology | |
| HP:0030302 | Agenesis of the anterior commissure | |
| HP:0008619 | Bilateral sensorineural hearing impairment | |
| HP:0001320 | Cerebellar vermis hypoplasia | |
| HP:0001491 | Congenital fibrosis of extraocular muscles | |
| HP:0002967 | Cubitus valgus | |
| HP:0012434 | Delayed social development | |
| HP:0000494 | Downslanted palpebral fissures | |
| HP:0001260 | Dysarthria | |
| HP:0025101 | Dysgenesis of the hippocampus | |
| HP:0001332 | Dystonia | |
| HP:0000712 | Emotional lability | |
| HP:0000286 | Epicanthus | |
| HP:0005469 | Flat occiput | |
| HP:0007359 | Focal-onset seizure | |
| HP:0002857 | Genu valgum | |
| HP:0030903 | Grasp reflex | |
| HP:0000218 | High palate | |
| HP:0040326 | Hypoplasia of the olfactory bulb | |
| HP:0005216 | Impaired mastication | |
| HP:0100785 | Insomnia | |
| HP:0001382 | Joint hypermobility | |
| HP:0002751 | Kyphoscoliosis | |
| HP:0007048 | Large basal ganglia | |
| HP:0006956 | Lateral ventricle dilatation | |
| HP:0000369 | Low-set ears | |
| HP:0000256 | Macrocephaly | |
| HP:0001840 | Metatarsus adductus | |
| HP:0000347 | Micrognathia | |
| HP:0002343 | Normal pressure hydrocephalus | |
| HP:0000657 | Oculomotor apraxia | |
| HP:0000609 | Optic nerve hypoplasia | |
| HP:0001357 | Plagiocephaly | |
| HP:0011451 | Primary microcephaly | |
| HP:0012760 | Reduced social responsiveness | |
| HP:0000407 | Sensorineural hearing impairment | |
| HP:0000736 | Short attention span | |
| HP:0001773 | Short foot | |
| HP:0012697 | Small basal ganglia | |
| HP:0200055 | Small hand | |
| HP:0001264 | Spastic diplegia | |
| HP:0002510 | Spastic tetraplegia | |
| HP:0002943 | Thoracic scoliosis | |
| HP:0000473 | Torticollis | |
| HP:0000572 | Visual loss | |
Run the differential on the 2 obligate / very frequent terms
Annotation source: 24860126[PMID]_26130693[PMID]_26739025[PMID]_26639658[PMID]_30016746[PMID]_28951247[PMID]_24932993[PMID]_27781032[PMID]_20074521[PMID]_20829227[PMID]
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Sources for this card
- Orphanet page: orpha.net/en/disease/detail/300570
- This record as JSON: /data/d/300570.json