ORPHA:496641
Early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome
- Type
- Malformation syndrome
- Group
- Disorder
- Inheritance
- Autosomal recessive
- Age of onset
- Infancy, Neonatal
- Status
- active
A rare, severe early-onset neurodegenerative encephalopathy characterized mainly by developmental delay (DD) / developmental regression (DR), epilepsy, cortical atrophy, secondary hypomyelination and thin corpus callosum. Additional features include secondary microcephaly, hypotonia, spasticity, optic atrophy and skeletal anomalies.
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Names in Orphadata languages
12 of 12 languages| Lang | Name | Synonyms |
|---|---|---|
| en | Early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome | |
| fr | Syndrome d'atrophie cérébrale diffuse précoce-microcéphalie-faiblesse musculaire-atrophie optique | |
| de | Früh beginnende progressive diffuse Gehirnatrophie-Mikrozephalie-Muskelschwäche-Optikusatrophie-Syndrom | |
| es | Síndrome de atrofia cerebral difusa progresiva de inicio precoz-microcefalia-debilidad muscular-atrofia óptica | |
| it | Sindrome atrofia cerebrale diffusa progressiva ad esordio precoce-microcefalia-debolezza muscolare-atrofia ottica | |
| nl | Progressieve diffuse hersenatrofie met vroege aanvang - microcefalie - spierzwakte - opticusatrofie-syndroom | |
| pt | Síndrome de atrofia cerebral difusa progressiva de início precoce-microcefalia-fraqueza muscular-atrofia óptica | |
| pl | Zespół wczesnej i postępującej rozsianej atrofii mózgu, osłabienia mięśniowego i zaniku nerwu wzrokowego | |
| cs | Syndrom zahrnující progresivní difuzní atrofii mozku s časným nástupem, mikrocefalii, svalovou slabost a atrofii optiků | |
| uk | Синдром ранньої прогресуючої дифузної атрофії головного мозку-мікроцефалії-мязової слабкості-атрофії зорового нерва | |
| zh | 早发型进行性弥漫性脑萎缩-小头肌-肌无力-视神经萎缩综合征 | |
| tr | Erken başlangıçlı ilerleyici yaygın beyin atrofisi-mikrosefali-kas güçsüzlüğü-optik atrofi sendromu |
Definition in:
2
Cross-references
qualifier = Orphanet mapping relation| Source | Code | Qualifier | ICD relation | Validation |
|---|---|---|---|---|
| OMIM | 617193 | E | validated | |
| ICD-10 | G93.4 | NTBT | attributed | validated |
| MONDO | 0044646 | E | validated | |
| UMLS | C5567454 | 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 (6):
- ORPHA:611327Genetic multiple congenital anomalies/dysmorphic syndrome-intellectual disability
rare genetic diseases - ORPHA:183500Genetic neurodegenerative disease
rare genetic diseases - ORPHA:166472Monogenic disease with epilepsy
rare genetic diseases; rare neurological diseases - ORPHA:102283Multiple congenital anomalies/dysmorphic syndrome-intellectual disability
rare developmental anomalies during embryogenesis; rare neurological diseases - ORPHA:182070Rare neurodegenerative disease
rare neurological diseases - ORPHA:441434Syndromic hereditary optic neuropathy
rare genetic diseases; rare ophthalmic disorders
No children.
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Genes
1 direct| Gene | Association | Status | HGNC | Ensembl | OMIM | Locus | Name | Source of validation |
|---|---|---|---|---|---|---|---|---|
| TBCD | Disease-causing germline mutation(s) (loss of function) in | Assessed | HGNC:11581 | ENSG00000141556 | 604649 | 17q25.3 | tubulin folding cofactor D | 27807845[PMID]_27666374[PMID]_27666370[PMID] |
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Prevalence and incidence
2 records| Type | Class | Value | Area | Qualification | Validation | Source |
|---|---|---|---|---|---|---|
| Cases/families | 39 cases | Worldwide | Case(s) | Validated | 27807845[PMID]_27666374[PMID]_27666370[PMID]_27928163[PMID] | |
| Point prevalence | <1 / 1 000 000 | — | Worldwide | Class only | Validated | ORPHANET_27807845[PMID]_27666374[PMID]_27666370[PMID]_27928163[PMID] |
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
56 annotations · validated 2019-07-11| HPO | Term (as annotated by Orphanet) | Diagnostic |
|---|---|---|
| Very frequent (99-80%) | ||
| HP:0002120 | Cerebral cortical atrophy | |
| HP:0001510 | Growth delay | |
| HP:0002079 | Hypoplasia of the corpus callosum | |
| HP:0001324 | Muscle weakness | |
| HP:0003202 | Skeletal muscle atrophy | |
| HP:0001257 | Spasticity | |
| Frequent (79-30%) | ||
| HP:0007179 | Absent smooth pursuit | |
| HP:0001344 | Absent speech | |
| HP:0002069 | Bilateral tonic-clonic seizure | |
| HP:0001272 | Cerebellar atrophy | |
| HP:0006808 | Cerebral hypomyelination | |
| HP:0011968 | Feeding difficulties | |
| HP:0008947 | Floppy infant | |
| HP:0010818 | Generalized tonic seizure | |
| HP:0001263 | Global developmental delay | |
| HP:0002187 | Intellectual disability, profound | |
| HP:0000648 | Optic atrophy | |
| HP:0002465 | Poor speech | |
| HP:0002191 | Progressive spasticity | |
| HP:0002878 | Respiratory failure | |
| HP:0005484 | Secondary microcephaly | |
| HP:0002445 | Tetraplegia | |
| Occasional (29-5%) | ||
| HP:0001284 | Areflexia | |
| HP:0002804 | Arthrogryposis multiplex congenita | |
| HP:0001251 | Ataxia | |
| HP:0012450 | Chronic constipation | |
| HP:0002376 | Developmental regression | |
| HP:0002015 | Dysphagia | |
| HP:0003236 | Elevated circulating creatine kinase concentration | |
| HP:0002380 | Fasciculations | |
| HP:0003084 | Fractures of the long bones | |
| HP:0000316 | Hypertelorism | |
| HP:0002342 | Intellectual disability, moderate | |
| HP:0000347 | Micrognathia | |
| HP:0001357 | Plagiocephaly | |
| HP:0001561 | Polyhydramnios | |
| HP:0011451 | Primary microcephaly | |
| HP:0004887 | Respiratory failure requiring assisted ventilation | |
| HP:0002650 | Scoliosis | |
| HP:0045075 | Sparse eyebrow | |
| HP:0000582 | Upslanted palpebral fissure | |
| HP:0000020 | Urinary incontinence | |
| HP:0000687 | Widely spaced teeth | |
| Very rare (<4-1%) | ||
| HP:0000733 | Abnormal repetitive mannerisms | |
| HP:0002607 | Bowel incontinence | |
| HP:0002524 | Cataplexy | |
| HP:0001374 | Congenital hip dislocation | |
| HP:0001332 | Dystonia | |
| HP:0002373 | Febrile seizure (within the age range of 3 months to 6 years) | |
| HP:0001007 | Hirsutism | |
| HP:0000400 | Macrotia | |
| HP:0007002 | Motor axonal neuropathy | |
| HP:0000011 | Neurogenic bladder | |
| HP:0000768 | Pectus carinatum | |
| HP:0000767 | Pectus excavatum | |
| HP:0006532 | Recurrent pneumonia | |
Run the differential on the 6 obligate / very frequent terms
Annotation source: 27807845[PMID]_27666370[PMID]_27666374[PMID]
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Sources for this card
- Orphanet page: orpha.net/en/disease/detail/496641
- This record as JSON: /data/d/496641.json