ORPHA:280763
Severe intellectual disability and progressive spastic paraplegia
Synonyms: AP-4 associated hereditary spastic paraplegia · AP4 deficiency syndrome
- Type
- Disease
- Group
- Disorder
- Inheritance
- Autosomal recessive
- Age of onset
- Infancy, Neonatal
- Status
- active
A rare complex hereditary spastic paraplegia characterized by an early onset hypotonia that progresses to spasticity, global developmental delay, severe intellectual disability and speech impairment, microcephaly, short stature and dysmorphic features. Patients often become non-ambulatory, and some develop seizures and stereotypic laughter.
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Names in Orphadata languages
12 of 12 languages| Lang | Name | Synonyms |
|---|---|---|
| en | Severe intellectual disability and progressive spastic paraplegia | AP-4 associated hereditary spastic paraplegia · AP4 deficiency syndrome |
| fr | Déficience intellectuelle sévère et paraplégie spastique progressive | Paraplégie spastique héréditaire associée à AP-4 · Syndrome de déficit en AP4 |
| de | Intelligenzminderung, schwere, mit progressiver spastischer Paraplegie | AP-4-assoziierte hereditäre spastische Paraplegie · AP4-Mangel-Syndrom |
| es | Discapacidad intelectual grave y paraplejía espástica progresiva | Paraplejía espástica hereditaria asociada a AP-4 · Síndrome de deficiencia de AP4 |
| it | Deficit cognitivo grave e paraplegia spastica progressiva | Sindrome da deficit di AP4 · Paraplegia spastica ereditaria associata all'AP-4 |
| nl | Ernstige intellectuele achterstand en progressieve spastische paraplegie | AP-4 geassocieerde hereditaire spastische paraplegie · AP4-deficiëntiesyndroom |
| pt | Perturbação do desenvolvimento intelectual grave e paraplegia espástica progressiva | Síndrome de deficiência de AP4 |
| pl | Ciężka niepełnosprawność intelektualna z postępującą paraplegią spastyczną | Zespół niedoboru AP4 |
| cs | Těžká mentální retardace a progresivní spastická paraplegie | Syndrom AP4 deficitu |
| uk | Тяжка розумова відсталість та прогресуюча спастична параплегія | Синдром дефіциту AP4 |
| zh | 严重智力障碍和进行性痉挛性截瘫 | AP4缺陷综合征 |
| tr | Ağır zihinsel yetersizlik ve ilerleyici spastik parapleji | AP4 eksikliği sendromu |
Definition in:
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Cross-references
qualifier = Orphanet mapping relation| Source | Code | Qualifier | ICD relation | Validation |
|---|---|---|---|---|
| OMIM | 612936 | BTNT | validated | |
| OMIM | 613744 | BTNT | validated | |
| OMIM | 614066 | BTNT | validated | |
| OMIM | 614067 | BTNT | validated | |
| ICD-10 | G11.4 | NTBT | attributed | validated |
| UMLS | C4755264 | E | validated | |
| GARD | 10999 | 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 (2):
- ORPHA:100981Autosomal recessive complex spastic paraplegia
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.
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Genes
4 direct| Gene | Association | Status | HGNC | Ensembl | OMIM | Locus | Name | Source of validation |
|---|---|---|---|---|---|---|---|---|
| AP4B1 | Disease-causing germline mutation(s) in | Assessed | HGNC:572 | ENSG00000134262 | 607245 | 1p13.2 | adaptor related protein complex 4 subunit beta 1 | 22290197[PMID]_21620353[PMID] |
| AP4E1 | Disease-causing germline mutation(s) in | Assessed | HGNC:573 | ENSG00000081014 | 607244 | 15q21.2 | adaptor related protein complex 4 subunit epsilon 1 | 20972249[PMID]_21620353[PMID] |
| AP4M1 | Disease-causing germline mutation(s) in | Assessed | HGNC:574 | ENSG00000221838 | 602296 | 7q22.1 | adaptor related protein complex 4 subunit mu 1 | 19559397[PMID] |
| AP4S1 | Disease-causing germline mutation(s) in | Assessed | HGNC:575 | ENSG00000100478 | 607243 | 14q12 | adaptor related protein complex 4 subunit sigma 1 | 21620353[PMID] |
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Prevalence and incidence
2 records| Type | Class | Value | Area | Qualification | Validation | Source |
|---|---|---|---|---|---|---|
| Cases/families | 15 cases | Worldwide | Case(s) | Validated | 21620353[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
37 annotations · validated 2018-11-05| HPO | Term (as annotated by Orphanet) | Diagnostic |
|---|---|---|
| Very frequent (99-80%) | ||
| HP:0001252 | Hypotonia | |
| HP:0010864 | Intellectual disability, severe | |
| HP:0000252 | Microcephaly | |
| HP:0007020 | Progressive spastic paraplegia | |
| Frequent (79-30%) | ||
| HP:0003487 | Babinski sign | |
| HP:0000414 | Bulbous nose | |
| HP:0001272 | Cerebellar atrophy | |
| HP:0002120 | Cerebral cortical atrophy | |
| HP:0000280 | Coarse facial features | |
| HP:0002307 | Drooling | |
| HP:0001332 | Dystonia | |
| HP:0000297 | Facial hypotonia | |
| HP:0001288 | Gait disturbance | |
| HP:0001263 | Global developmental delay | |
| HP:0001347 | Hyperreflexia | |
| HP:0002465 | Poor speech | |
| HP:0004322 | Short stature | |
| HP:0002464 | Spastic dysarthria | |
| HP:0001257 | Spasticity | |
| HP:0002515 | Waddling gait | |
| Occasional (29-5%) | ||
| HP:0002518 | Abnormal periventricular white matter morphology | |
| HP:0000733 | Abnormal repetitive mannerisms | |
| HP:0010803 | Everted upper lip vermilion | |
| HP:0000218 | High palate | |
| HP:0002079 | Hypoplasia of the corpus callosum | |
| HP:0000341 | Narrow forehead | |
| HP:0025502 | Overweight | |
| HP:0001763 | Pes planus | |
| HP:0001250 | Seizure | |
| HP:0000322 | Short philtrum | |
| HP:0100962 | Shyness | |
| HP:0000154 | Wide mouth | |
| Very rare (<4-1%) | ||
| HP:0008807 | Acetabular dysplasia | |
| HP:0000646 | Amblyopia | |
| HP:0002761 | Generalized joint hypermobility | |
| HP:0002816 | Genu recurvatum | |
| HP:0000486 | Strabismus | |
Run the differential on the 4 obligate / very frequent terms
Annotation source: 21620353[PMID]_19559397[PMID]_25552650[PMID]
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Sources for this card
- Orphanet page: orpha.net/en/disease/detail/280763
- This record as JSON: /data/d/280763.json