ORPHA:2254
Pontocerebellar hypoplasia type 1
Synonyms: Norman disease · PCH1
- Type
- Clinical subtype
- Group
- Subtype of disorder
- Inheritance
- Autosomal recessive
- Age of onset
- Neonatal
- Status
- active
A severe, genetic form of pontocerebellar hypoplasia (PCH) characterized by spinal cord anterior horn cell degeneration in addition to pontocerebellar hypoplasia. Clinically, patients manifest with a severe global development deficit that is evident early on from difficulties in feeding and swallowing
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Names in Orphadata languages
12 of 12 languages| Lang | Name | Synonyms |
|---|---|---|
| en | Pontocerebellar hypoplasia type 1 | Norman disease · PCH1 |
| fr | Hypoplasie pontocérébelleuse type 1 | HPC1 · PCH1 |
| de | Pontozerebelläre Hypoplasie Typ 1 | Norman-Krankheit · PCH1 |
| es | Hipoplasia pontocerebelosa tipo 1 | Enfermedad de Norman · HPC1 |
| it | Ipoplasia pontocerebellare, tipo 1 | Malattia di Norman · PCH1 |
| nl | Pontocerebellaire hypoplasie type 1 | PCH1 · Ziekte van Norman |
| pt | Hipoplasia pontocerebelosa tipo 1 | |
| pl | Hipolplazja mostu i móżdżku typu 1 | Choroba Normana · PCH1 |
| cs | Pontocerebelární hypoplázie, typ 1 | Normanova nemoc · PCH1 |
| uk | Гіпоплазія мозочка, тип 1 | Хвороба Нормана · PCH1 |
| zh | 脑桥小脑发育不全1型 | Norman 病 |
| tr | Pontoserebellar hipoplazi tip 1 | PCH1 · Norman hastalığı |
Definition in:
2
Cross-references
qualifier = Orphanet mapping relation| Source | Code | Qualifier | ICD relation | Validation |
|---|---|---|---|---|
| OMIM | 607596 | BTNT | validated | |
| OMIM | 614678 | BTNT | validated | |
| OMIM | 616081 | BTNT | validated | |
| OMIM | 618065 | BTNT | validated | |
| OMIM | 619303 | BTNT | validated | |
| OMIM | 619304 | BTNT | validated | |
| ICD-10 | Q04.3 | NTBT | attributed | validated |
| ICD-11 | LD20.01 | NTBT | index | validated |
| MONDO | 0016396 | E | validated | |
| MeSH | C548069 | E | validated | |
| UMLS | C5442006 | E | validated | |
| GARD | 10704 | 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:98523Pontocerebellar hypoplasia
rare developmental anomalies during embryogenesis; rare genetic diseases; rare neurological diseases - ORPHA:207012Spinal muscular atrophy associated with central nervous system anomaly
rare genetic diseases; rare neurological diseases
No children.
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Genes
6 direct| Gene | Association | Status | HGNC | Ensembl | OMIM | Locus | Name | Source of validation |
|---|---|---|---|---|---|---|---|---|
| SLC25A46 | Disease-causing germline mutation(s) (loss of function) in | Assessed | HGNC:25198 | ENSG00000164209 | 610826 | 5q22.1 | solute carrier family 25 member 46 | 28637197[PMID] |
| AGTPBP1 | Disease-causing germline mutation(s) in | Assessed | HGNC:17258 | ENSG00000135049 | 606830 | 9q21.33 | ATP/GTP binding carboxypeptidase 1 | 30976113[PMID] |
| EXOSC3 | Disease-causing germline mutation(s) in | Assessed | HGNC:17944 | ENSG00000107371 | 606489 | 9p13.2 | exosome component 3 | 22544365[PMID]_25144110[PMID] |
| EXOSC8 | Disease-causing germline mutation(s) in | Assessed | HGNC:17035 | ENSG00000120699 | 606019 | 13q13.3 | exosome component 8 | 24989451[PMID] |
| EXOSC9 | Disease-causing germline mutation(s) in | Assessed | HGNC:9137 | ENSG00000123737 | 606180 | 4q27 | exosome component 9 | 29727687[PMID] |
| VRK1 | Disease-causing germline mutation(s) in | Assessed | HGNC:12718 | ENSG00000100749 | 602168 | 14q32.2 | VRK serine/threonine kinase 1 | 19646678[PMID] |
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Prevalence and incidence
2 records| Type | Class | Value | Area | Qualification | Validation | Source |
|---|---|---|---|---|---|---|
| Cases/families | 40 families | Worldwide | Family(ies) | Validated | [EXPERT] | |
| 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
29 annotations · validated 2022-09-16| HPO | Term (as annotated by Orphanet) | Diagnostic |
|---|---|---|
| Very frequent (99-80%) | ||
| HP:0007360 | Aplasia/Hypoplasia of the cerebellum | |
| HP:0002398 | Degeneration of anterior horn cells | |
| HP:0001263 | Global developmental delay | |
| HP:0001265 | Hyporeflexia | |
| HP:0001252 | Hypotonia | |
| HP:0001270 | Motor delay | |
| HP:0001324 | Muscle weakness | |
| HP:0002878 | Respiratory failure | |
| HP:0003202 | Skeletal muscle atrophy | |
| Frequent (79-30%) | ||
| HP:0001508 | Failure to thrive | |
| HP:0011968 | Feeding difficulties | |
| HP:0012110 | Hypoplasia of the pons | |
| HP:0000639 | Nystagmus | |
| HP:0000648 | Optic atrophy | |
| HP:0000253 | Progressive microcephaly | |
| HP:0000529 | Progressive visual loss | |
| Occasional (29-5%) | ||
| HP:0002350 | Cerebellar cyst | |
| HP:0002120 | Cerebral cortical atrophy | |
| HP:0004886 | Congenital laryngeal stridor | |
| HP:0001347 | Hyperreflexia | |
| HP:0003477 | Peripheral axonal neuropathy | |
| HP:0001250 | Seizure | |
| HP:0001257 | Spasticity | |
| HP:0000486 | Strabismus | |
| HP:0033725 | Thin corpus callosum | |
| HP:0001308 | Tongue fasciculations | |
| Very rare (<4-1%) | ||
| HP:0002804 | Arthrogryposis multiplex congenita | |
| HP:0001251 | Ataxia | |
| HP:0000565 | Esotropia | |
Run the differential on the 9 obligate / very frequent terms
Annotation source: 29656927[PMID]_35893425[PMID]_35852507[PMID]_24989451[PMID]
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Sources for this card
- Orphanet page: orpha.net/en/disease/detail/2254
- This record as JSON: /data/d/2254.json