ORPHA:289494

4H leukodystrophy

Synonyms: POLR-related leukodystrophy

Type: Disease
Group: Disorder
Age of onset: Adolescent, Adult, Childhood, Infancy
Status: active

A rare hypomyelinating leukodystrophy disorder characterized by the association of dental abnormalities (delayed dentition, abnormal order of dentition, hypodontia), hypogonadotropic hypogonadism, and hypomyelinating leukodystrophy manifesting with neurodevelopmental delay or regression and/or progressive cerebellar symptoms.

Names in Orphadata languages

12 of 12 languages

Lang	Name	Synonyms
en	4H leukodystrophy	POLR-related leukodystrophy
fr	Leucodystrophie 4H	Leucodystrophie hypomyélinisante associée à POLR
de	4H-Leukodystrophie	4H-Syndrom · POLR-assoziierte Leukodystrophie
es	Leucodistrofia 4H	Leucodistrofia asociada a POLR
it	Leucodistrofia 4H	Leucodistrofia Pol III-correlata
nl	4H-leukodystrofie	POLR-gerelateerde leukodystrofie
pt	Leucodistrofia hipomielinizante com ou sem oligondontia e/ou hipogonadismo
pl	Leukodystrofia hipomielinizująca z lub bez oligodoncji i/lub hipogonadyzmem	Leukodystrofia związna z Pol III
cs	Hypomyelinizační leukodystrofie s/bez oligodontie a/nebo hypogonadizmem	Pol III-vázaná leukodystrofie
uk	4H лейкодистрофія	POLR-асоційована лейкодистрофія
zh	4H型脑白质营养不良	POLR相关脑白质营养不良
tr	4H lökodistrofi	POLR-ilişkili lökodistrofi

Definition in:

Cross-references

qualifier = Orphanet mapping relation

Source	Code	Qualifier	ICD relation	Validation
OMIM	607694	BTNT		validated
OMIM	614381	BTNT		validated
OMIM	616494	BTNT		validated
ICD-10	G37.8	NTBT	attributed	validated
ICD-11	8A44.Z	NTBT	index	validated
MONDO	100605	E		validated
UMLS	C5679947	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):

ORPHA:98006Rare neurologic disease

Parents in the classifications (1):

ORPHA:68356Leukodystrophy
rare genetic diseases; rare neurological diseases

Children (5):

Genes

0 direct · 7 via subtypes

Orphanet records no gene directly on this code.

Recorded by Orphanet on subtypes of this disorder:

Gene	Subtype	Association	Status	HGNC	Ensembl	OMIM	Locus	Name	Source of validation
POLR1C	ORPHA:88637Hypomyelination-hypogonadotropic hypogonadism-hypodontia syndrome	Disease-causing germline mutation(s) in	Assessed	HGNC:20194	ENSG00000171453	610060	6p21.1	RNA polymerase I and III subunit C	26151409[PMID]
POLR3A	ORPHA:77295Odontoleukodystrophy	Disease-causing germline mutation(s) in	Assessed	HGNC:30074	ENSG00000148606	614258	10q22.3	RNA polymerase III subunit A	21855841[PMID]_22855961[PMID]
POLR3A	ORPHA:88637Hypomyelination-hypogonadotropic hypogonadism-hypodontia syndrome	Disease-causing germline mutation(s) in	Assessed	HGNC:30074	ENSG00000148606	614258	10q22.3	RNA polymerase III subunit A	21855841[PMID]_22855961[PMID]
POLR3A	ORPHA:137639Hypomyelinating leukodystrophy-ataxia-hypodontia-hypomyelination syndrome	Disease-causing germline mutation(s) in	Assessed	HGNC:30074	ENSG00000148606	614258	10q22.3	RNA polymerase III subunit A	27506977[PMID]
POLR3A	ORPHA:447893Hypomyelination-cerebellar atrophy-hypoplasia of the corpus callosum syndrome	Disease-causing germline mutation(s) in	Assessed	HGNC:30074	ENSG00000148606	614258	10q22.3	RNA polymerase III subunit A	22036171[PMID]
POLR3A	ORPHA:447896Tremor-ataxia-central hypomyelination syndrome	Disease-causing germline mutation(s) in	Assessed	HGNC:30074	ENSG00000148606	614258	10q22.3	RNA polymerase III subunit A	20640464[PMID]
POLR3B	ORPHA:88637Hypomyelination-hypogonadotropic hypogonadism-hypodontia syndrome	Disease-causing germline mutation(s) in	Assessed	HGNC:30348	ENSG00000013503	614366	12q23.3	RNA polymerase III subunit B	22855961[PMID]_22036172[PMID]

Prevalence and incidence

2 records

Type	Class	Value	Area	Qualification	Validation	Source
Point prevalence	Unknown	—	Worldwide	Class only	Validated	ORPHANET_[EXPERT]
Cases/families		200 cases	Worldwide	Case(s)	Validated	[EXPERT]_22855961[PMID]_25339210[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

32 annotations · validated 2021-03-31

HPO	Term (as annotated by Orphanet)	Diagnostic
Very frequent (99-80%)
HP:0000164	Abnormality of the dentition
HP:0001251	Ataxia
HP:0006808	Cerebral hypomyelination
HP:0001260	Dysarthria
HP:0001332	Dystonia
HP:0000668	Hypodontia
HP:0000044	Hypogonadotropic hypogonadism
HP:0000545	Myopia
Frequent (79-30%)
HP:0002071	Abnormality of extrapyramidal motor function
HP:0000496	Abnormality of eye movement
HP:0000823	Delayed puberty
HP:0002307	Drooling
HP:0002015	Dysphagia
HP:0030890	Hyperintensity of cerebral white matter on MRI
HP:0007240	Progressive gait ataxia
HP:0004322	Short stature
HP:0001337	Tremor
HP:0002493	Upper motor neuron dysfunction
Occasional (29-5%)
HP:0000570	Abnormal saccadic eye movements
HP:0002926	Abnormality of thyroid physiology
HP:0001272	Cerebellar atrophy
HP:0000824	Decreased response to growth hormone stimulation test
HP:0000684	Delayed eruption of teeth
HP:0002075	Dysdiadochokinesis
HP:0001310	Dysmetria
HP:0000640	Gaze-evoked nystagmus
HP:0002079	Hypoplasia of the corpus callosum
HP:0001268	Mental deterioration
HP:0001250	Seizure
Very rare (<4-1%)
HP:0000518	Cataract
HP:0000648	Optic atrophy
HP:0031206	Striatal T2 hyperintensity

Run the differential on the 8 obligate / very frequent terms

Annotation source: 22855961[PMID]_33005949[PMID]_31768296[PMID]

Sources for this card

Orphanet page: orpha.net/en/disease/detail/289494
This record as JSON: /data/d/289494.json