Early-onset progressive encephalopathy-spastic ataxia-distal spinal muscular atrophy syndrome
- Type
- Disease
- Group
- Disorder
- Inheritance
- Autosomal recessive
- Age of onset
- Infancy, Neonatal
- Status
- active
A rare genetic neurodegenerative disease characterized by neonatal to infantile onset of hypotonia, developmental delay, regression of motor skills with distal amyotrophy, ataxia, and spasticity, absent speech or dysarthria, and moderate to severe cognitive impairment. Optic atrophy may also be associated. Brain imaging shows cerebellar atrophy and thin corpus callosum, as well as brain iron accumulation in the pallidum and substantia nigra beginning during the second decade of life.
Names in Orphadata languages
12 of 12 languages| Lang | Name | Synonyms |
|---|---|---|
| en | Early-onset progressive encephalopathy-spastic ataxia-distal spinal muscular atrophy syndrome | |
| fr | Syndrome d'encéphalopathie progressive à début précoce-ataxie spastique-amyotrophie spinale distale | |
| de | Früh-beginnende progressive Enzephalopathie-spastische Ataxie-distale spinale Muskelatrophie-Syndrom | |
| es | Síndrome de encefalopatía progresiva-ataxia espástica-atrofia muscular espinal distal de inicio precoz | |
| it | Sindrome encefalopatia progressiva ad esordio precoce-atassia spastica-atrofia muscolare spinale distale | |
| nl | Progressieve encefalopathie met vroege aanvang - spastische ataxie - distale spinale musculaire atrofie-syndroom | |
| pt | Síndrome de encefalopatia progressiva de início precoce-ataxia espástica-atrofia muscular espinhal distal | |
| pl | Zespół wczesnej i postępującej encefalopatii, ataksji spastycznej, dystalnej atrofii mięśniowo-rdzeniowej | |
| cs | Syndrom zahrnující progresivní encefalopatii s časným nástupem, spastickou ataxii a spinální muskulární atrofii | |
| uk | Синдром ранньої прогресуючої енцефалопатії-спастичної атаксії-дистальної спінальної мязової атрофії | |
| zh | 早发性进行性脑病-痉挛性共济失调-远端脊髓性肌萎缩症 | |
| tr | Erken başlangıçlı ilerleyici ensefalopati-spastik ataksi-distal spinal musküler atrofi sendromu |
Definition in:
Cross-references
qualifier = Orphanet mapping relation| Source | Code | Qualifier | ICD relation | Validation |
|---|---|---|---|---|
| OMIM | 617207 | E | validated | |
| ICD-10 | G31.8 | NTBT | attributed | validated |
| MONDO | 0044651 | E | validated | |
| UMLS | C5567451 | E | validated |
E exact · NTBT this ORPHAcode is narrower than the target · BTNT broader than the target · ND not decided.
Classification
Preferential parent (Orphanet linearisation):
Parents in the classifications (4):
- ORPHA:98098Autosomal recessive degenerative and progressive cerebellar ataxia
rare genetic diseases; rare neurological diseases - ORPHA:140468Autosomal recessive distal hereditary motor neuropathy
rare genetic diseases; rare neurological diseases - ORPHA:385Neurodegeneration with brain iron accumulation
rare genetic diseases; rare neurological diseases - ORPHA:611314Rare syndromic intellectual disability without multiple congenital anomalies/dysmorphic syndrome
rare genetic diseases; rare neurological diseases
No children.
Genes
1 direct| Gene | Association | Status | HGNC | Ensembl | OMIM | Locus | Name | Source of validation |
|---|---|---|---|---|---|---|---|---|
| TBCE | Disease-causing germline mutation(s) in | Assessed | HGNC:11582 | ENSG00000284770 | 604934 | 1q42.3 | tubulin folding cofactor E | 27666369[PMID] |
Prevalence and incidence
2 records| Type | Class | Value | Area | Qualification | Validation | Source |
|---|---|---|---|---|---|---|
| Cases/families | 6 cases | Worldwide | Case(s) | Validated | 27666369[PMID] | |
| Point prevalence | <1 / 1 000 000 | — | Worldwide | Class only | Validated | ORPHANET_27666369[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.
HPO phenotypes
24 annotations · validated 2018-11-26| HPO | Term (as annotated by Orphanet) | Diagnostic |
|---|---|---|
| Very frequent (99-80%) | ||
| HP:0003693 | Distal amyotrophy | Diagnostic criterion |
| HP:0002448 | Progressive encephalopathy | Diagnostic criterion |
| HP:0002497 | Spastic ataxia | Diagnostic criterion |
| HP:0007269 | Spinal muscular atrophy | Diagnostic criterion |
| Frequent (79-30%) | ||
| HP:0001272 | Cerebellar atrophy | |
| HP:0002376 | Developmental regression | |
| HP:0003698 | Difficulty standing | |
| HP:0001260 | Dysarthria | |
| HP:0003444 | EMG: chronic denervation signs | |
| HP:0009027 | Foot dorsiflexor weakness | |
| HP:0001290 | Generalized hypotonia | |
| HP:0001263 | Global developmental delay | |
| HP:0002079 | Hypoplasia of the corpus callosum | |
| HP:0001249 | Intellectual disability | |
| HP:0003477 | Peripheral axonal neuropathy | |
| Occasional (29-5%) | ||
| HP:0002425 | Anarthria | |
| HP:0012678 | Iron accumulation in substantia nigra | |
| HP:0000648 | Optic atrophy | |
| HP:0007199 | Progressive spastic paraparesis | |
| HP:0002650 | Scoliosis | |
| HP:0001285 | Spastic tetraparesis | |
| Very rare (<4-1%) | ||
| HP:0001250 | Seizure | |
| Excluded (0%) | ||
| HP:0001510 | Growth delay | |
| HP:0000829 | Hypoparathyroidism | |
Run the differential on the 4 obligate / very frequent terms
Annotation source: 27666369[PMID]
Sources for this card
- Orphanet page: orpha.net/en/disease/detail/496756
- This record as JSON: /data/d/496756.json