NKX6-2-related autosomal recessive hypomyelinating leukodystrophy
Synonyms: Autosomal recessive hypomyelinating leukodystrophy-progressive spastic ataxia · SPAX8
- Type
- Disease
- Group
- Disorder
- Inheritance
- Autosomal recessive
- Age of onset
- Childhood, Infancy
- Status
- active
A rare leukodystrophy characterized by a spectrum of progressive neurologic manifestations comprising rapidly progressive early-onset nystagmus, spastic tetraplegia, and visual and hearing impairment, resulting in death in early childhood, as well as later onset of slowly progressive complex spastic ataxia with pyramidal and cerebellar symptoms and loss of developmental milestones. Brain imaging shows diffuse hypomyelination of the subcortical and deep white matter, cerebellar atrophy, and diffuse spinal cord volume loss.
Names in Orphadata languages
12 of 12 languages| Lang | Name | Synonyms |
|---|---|---|
| en | NKX6-2-related autosomal recessive hypomyelinating leukodystrophy | Autosomal recessive hypomyelinating leukodystrophy-progressive spastic ataxia · SPAX8 |
| fr | Leucodystrophie hypomyélinisante autosomique récessive associée à NKX6-2 | Leucodystrophie hypomyélinisante autosomique récessive-ataxie spastique progressive · SPAX8 |
| de | NKX6-2-assoziierte autosomal-rezessive hypomyelinisierende Leukodystrophie | SPAX8 |
| es | Leucodistrofia hipomielinizante autosómica recesiva asociada a NKX6-2 | Leucodistrofia hipomielinizante autosómica recesiva-ataxia espástica progresiva · SPAX8 |
| it | Leucodistrofia ipomielinizzante autosomica recessiva correlata a NKX6-2 | Leucodistrofia ipomielinizzante - atassia spastica progressiva autosomica recessiva · SPAX8 |
| nl | NKX6-2-gerelateerde autosomaal recessieve hypomyeliniserende leukodystrofie | Autosomaal recessieve hypomyeliniserende leukodystrofie - progressieve spastische ataxie · SPAX8 |
| pt | Leucodistrofia hipomielinizante autossómica recessiva NKX6-2-relacionada | |
| pl | Autosomalna, recesywna leukodystrofia hipomielinizująca związana z NKX6-2 | SPAX8 · Autosomalna, recesywna leukodystrofia hipomielinizująca-postępująca ataksja/niezborność spastyczna |
| cs | NKX6-vázaná autozomálně recesivní hypomyelinizační leukodystrofie | SPAX8 · Autozomálně recesivní hypomyelinizační leukodystrofie a progresivní spastická ataxie |
| uk | NKX6-2-повязана аутосомно-рецесивна гіпомієлінізуюча лейкодистрофія | Аутосомно-рецесивна гіпомієлінізуюча лейкодистрофія - прогресуюча спастична атаксія · SPAX8 |
| zh | NKX6-2基因相关的常染色体隐性低髓鞘化脑白质营养不良症 | = en |
| tr | NKX6-2-ilişkili otozomal resesif hipomiyelinizan lökodistrofi | Otozomal çekinik hipomyelinizan lökodistrofi-ilerleyici spastik ataksi · SPAX8 |
Definition in:
Cross-references
qualifier = Orphanet mapping relation| Source | Code | Qualifier | ICD relation | Validation |
|---|---|---|---|---|
| OMIM | 617560 | E | validated | |
| ICD-10 | E75.2 | NTBT | attributed | validated |
| MONDO | 0033043 | E | validated | |
| UMLS | C4479653 | 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 (3):
- ORPHA:316240Autosomal recessive spastic ataxia
rare genetic diseases; rare neurological diseases - ORPHA:68356Leukodystrophy
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 |
|---|---|---|---|---|---|---|---|---|
| NKX6-2 | Disease-causing germline mutation(s) in | Assessed | HGNC:19321 | ENSG00000148826 | 605955 | 10q26.3 | NK6 homeobox 2 | 28575651[PMID] |
Prevalence and incidence
2 records| Type | Class | Value | Area | Qualification | Validation | Source |
|---|---|---|---|---|---|---|
| Cases/families | 25 cases | Worldwide | Case(s) | Validated | 29388673[PMID]_30285346[PMID] | |
| Point prevalence | <1 / 1 000 000 | — | Worldwide | Class only | Validated | ORPHANET_29388673[PMID]_30285346[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
25 annotations · validated 2019-03-27| HPO | Term (as annotated by Orphanet) | Diagnostic |
|---|---|---|
| Very frequent (99-80%) | ||
| HP:0007256 | Abnormal pyramidal sign | |
| HP:0001251 | Ataxia | |
| HP:0000571 | Hypometric saccades | |
| HP:0000639 | Nystagmus | |
| Frequent (79-30%) | ||
| HP:0003429 | CNS hypomyelination | |
| HP:0001260 | Dysarthria | |
| HP:0001332 | Dystonia | |
| HP:0001288 | Gait disturbance | |
| HP:0001290 | Generalized hypotonia | |
| HP:0001263 | Global developmental delay | |
| HP:0002599 | Head titubation | |
| HP:0030890 | Hyperintensity of cerebral white matter on MRI | |
| HP:0001347 | Hyperreflexia | |
| HP:0002415 | Leukodystrophy | |
| HP:0007704 | Paroxysmal involuntary eye movements | |
| HP:0002191 | Progressive spasticity | |
| Occasional (29-5%) | ||
| HP:0001272 | Cerebellar atrophy | |
| HP:0002059 | Cerebral atrophy | |
| HP:0001007 | Hirsutism | |
| HP:0002650 | Scoliosis | |
| HP:0001250 | Seizure | |
| HP:0000486 | Strabismus | |
| Very rare (<4-1%) | ||
| HP:0002079 | Hypoplasia of the corpus callosum | |
| HP:0001249 | Intellectual disability | |
| Excluded (0%) | ||
| HP:0012534 | Dysesthesia | |
Run the differential on the 4 obligate / very frequent terms
Annotation source: 29388673[PMID]_30285346[PMID]
Sources for this card
- Orphanet page: orpha.net/en/disease/detail/527497
- This record as JSON: /data/d/527497.json