ORPHA:135

CACH syndrome

Synonyms: Childhood ataxia with diffuse central nervous system hypomyelination · Leukoencephalopathy with vanishing white matter · Myelinosis centralis diffusa

Type: Disease
Group: Disorder
Inheritance: Autosomal recessive
Age of onset: Childhood
Status: active

A new leukoencephalopathy, the CACH syndrome (Childhood Ataxia with Central nervous system Hypomyelination) or VWM (Vanishing White Matter) was identified on clinical and MRI criteria. Classically, this disease is characterized by (1) an onset between 2 and 5 years of age, with a cerebello-spastic syndrome exacerbated by episodes of fever or head trauma leading to death after 5 to 10 years of disease evolution, (2) a diffuse involvement of the white matter on cerebral MRI with a CSF-like signal intensity (cavitation), (3) a recessive autosomal mode of inheritance, (4) neuropathologic findings consistent with a cavitating orthochromatic leukodystrophy with increased number of oligodendrocytes with sometimes ``foamy'' aspect.

Names in Orphadata languages

12 of 12 languages

Lang	Name	Synonyms
en	CACH syndrome	Childhood ataxia with diffuse central nervous system hypomyelination · Leukoencephalopathy with vanishing white matter · Myelinosis centralis diffusa
fr	Syndrome CACH	Ataxie infantile avec hypomyélinisation diffuse du système nerveux central · Leucoencéphalopathie avec perte de substance blanche · Myélinolyse centrale diffuse
de	CACH-Syndrom	Infantile Ataxie mit diffuser Hypomyelinisierung des ZNS · Leukoenzephalopathie mit Verlust der weissen Hirnsubstanz · Myelinosis centralis diffusa
es	Síndrome CACH	Ataxia infantil con hipomielinización del sistema nervioso central · Leucoencefalopatía con desaparición de la sustancia blanca · Mielinosis central difusa
it	Sindrome CACH	Atassia infantile con ipomielinizzazione diffusa del sistema nervoso centrale · Leucoencefalopatia con perdita della sostanza bianca · Mielinolisi centrale diffusa
nl	CACH-syndroom	Ataxie op kinderleeftijd met diffuse hypomyelinisatie van centraal zenuwstelsel · Leuko-encefalopathie met verdwijnende witte stof · Myelinosis centralis diffusa
pt	Síndrome CACH	Ataxia infantil com hipomielinização difusa do SNC · Leucoencefalopatia com desaparecimento de substância branca · Mielinose central difusa
pl	Zespół CACH	Dziecięca ataksja z rozlaną hipomielinizacją centralnego układu nerwowego · Leukoencefalopatia z zanikającą istotą białą · Myelinosis centralis diffusa
cs	CACH syndrom	Leukoencefalopatie s mizející bílou hmotou · Myelinosis centralis diffusa · Dětská ataxie s difuzní hypomyelinizací centrálního nervového systému
uk	CACH-синдром	Дитяча атаксія з дифузною гіпомієлінізацією центральної нервової системи · Лейкоенцефалопатія зі зникненням білої речовини · Центральний дифузний мієліноз
zh	CACH综合征	弥漫性中枢神经系统髓鞘形成减少伴儿童期共济失调
tr	CACH sendromu	Myelinozis sentralis diffusa · Kaybolan beyaz cevher ile seyreden lökoensefalopati · Yaygın merkezi sinir sistemi hipomiyelinizasyon ile seyreden çocukluk çağı ataksisi

Definition in:

Cross-references

qualifier = Orphanet mapping relation

Source	Code	Qualifier	ICD relation	Validation
OMIM	603896	E		validated
OMIM	615889	BTNT		validated
OMIM	620312	BTNT		validated
OMIM	620313	BTNT		validated
OMIM	620314	BTNT		validated
OMIM	620315	BTNT		validated
ICD-10	E75.2	NTBT	attributed	validated
ICD-11	8A44.3	NTBT	index	validated
MONDO	0800448	E		validated
UMLS	C1858991	E		validated
GARD	231	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 · 26 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
AARS2	ORPHA:99853Ovarioleukodystrophy	Disease-causing germline mutation(s) (loss of function) in	Assessed	HGNC:21022	ENSG00000124608	612035	6p21.1	alanyl-tRNA synthetase 2, mitochondrial	24808023[PMID]
EIF2B1	ORPHA:99853Ovarioleukodystrophy	Disease-causing germline mutation(s) in	Assessed	HGNC:3257	ENSG00000111361	606686	12q24.31	eukaryotic translation initiation factor 2B subunit alpha	20301435[PMID]_15136673[PMID]
EIF2B1	ORPHA:99854Cree leukoencephalopathy	Disease-causing germline mutation(s) in	Assessed	HGNC:3257	ENSG00000111361	606686	12q24.31	eukaryotic translation initiation factor 2B subunit alpha	20301435[PMID]_15136673[PMID]
EIF2B1	ORPHA:157713Congenital or early infantile CACH syndrome	Disease-causing germline mutation(s) in	Assessed	HGNC:3257	ENSG00000111361	606686	12q24.31	eukaryotic translation initiation factor 2B subunit alpha	20301435[PMID]
EIF2B1	ORPHA:157716Late infantile CACH syndrome	Disease-causing germline mutation(s) in	Assessed	HGNC:3257	ENSG00000111361	606686	12q24.31	eukaryotic translation initiation factor 2B subunit alpha	20301435[PMID]
EIF2B1	ORPHA:157719Juvenile or adult CACH syndrome	Disease-causing germline mutation(s) in	Assessed	HGNC:3257	ENSG00000111361	606686	12q24.31	eukaryotic translation initiation factor 2B subunit alpha	20301435[PMID]
EIF2B2	ORPHA:99853Ovarioleukodystrophy	Disease-causing germline mutation(s) in	Assessed	HGNC:3258	ENSG00000119718	606454	14q24.3	eukaryotic translation initiation factor 2B subunit beta	20301435[PMID]_15136673[PMID]
EIF2B2	ORPHA:99854Cree leukoencephalopathy	Disease-causing germline mutation(s) in	Assessed	HGNC:3258	ENSG00000119718	606454	14q24.3	eukaryotic translation initiation factor 2B subunit beta	20301435[PMID]_15136673[PMID]
EIF2B2	ORPHA:157713Congenital or early infantile CACH syndrome	Disease-causing germline mutation(s) in	Assessed	HGNC:3258	ENSG00000119718	606454	14q24.3	eukaryotic translation initiation factor 2B subunit beta	20301435[PMID]
EIF2B2	ORPHA:157716Late infantile CACH syndrome	Disease-causing germline mutation(s) in	Assessed	HGNC:3258	ENSG00000119718	606454	14q24.3	eukaryotic translation initiation factor 2B subunit beta	20301435[PMID]
EIF2B2	ORPHA:157719Juvenile or adult CACH syndrome	Disease-causing germline mutation(s) in	Assessed	HGNC:3258	ENSG00000119718	606454	14q24.3	eukaryotic translation initiation factor 2B subunit beta	20301435[PMID]
EIF2B3	ORPHA:99853Ovarioleukodystrophy	Disease-causing germline mutation(s) in	Assessed	HGNC:3259	ENSG00000070785	606273	1p34.1	eukaryotic translation initiation factor 2B subunit gamma	20301435[PMID]_15136673[PMID]
EIF2B3	ORPHA:99854Cree leukoencephalopathy	Disease-causing germline mutation(s) in	Assessed	HGNC:3259	ENSG00000070785	606273	1p34.1	eukaryotic translation initiation factor 2B subunit gamma	20301435[PMID]_15136673[PMID]
EIF2B3	ORPHA:157713Congenital or early infantile CACH syndrome	Disease-causing germline mutation(s) in	Assessed	HGNC:3259	ENSG00000070785	606273	1p34.1	eukaryotic translation initiation factor 2B subunit gamma	20301435[PMID]
EIF2B3	ORPHA:157716Late infantile CACH syndrome	Disease-causing germline mutation(s) in	Assessed	HGNC:3259	ENSG00000070785	606273	1p34.1	eukaryotic translation initiation factor 2B subunit gamma	20301435[PMID]
EIF2B3	ORPHA:157719Juvenile or adult CACH syndrome	Disease-causing germline mutation(s) in	Assessed	HGNC:3259	ENSG00000070785	606273	1p34.1	eukaryotic translation initiation factor 2B subunit gamma	20301435[PMID]
EIF2B4	ORPHA:99853Ovarioleukodystrophy	Disease-causing germline mutation(s) in	Assessed	HGNC:3260	ENSG00000115211	606687	2p23.3	eukaryotic translation initiation factor 2B subunit delta	20301435[PMID]_15136673[PMID]
EIF2B4	ORPHA:99854Cree leukoencephalopathy	Disease-causing germline mutation(s) in	Assessed	HGNC:3260	ENSG00000115211	606687	2p23.3	eukaryotic translation initiation factor 2B subunit delta	20301435[PMID]_15136673[PMID]
EIF2B4	ORPHA:157713Congenital or early infantile CACH syndrome	Disease-causing germline mutation(s) in	Assessed	HGNC:3260	ENSG00000115211	606687	2p23.3	eukaryotic translation initiation factor 2B subunit delta	20301435[PMID]
EIF2B4	ORPHA:157716Late infantile CACH syndrome	Disease-causing germline mutation(s) in	Assessed	HGNC:3260	ENSG00000115211	606687	2p23.3	eukaryotic translation initiation factor 2B subunit delta	20301435[PMID]
EIF2B4	ORPHA:157719Juvenile or adult CACH syndrome	Disease-causing germline mutation(s) in	Assessed	HGNC:3260	ENSG00000115211	606687	2p23.3	eukaryotic translation initiation factor 2B subunit delta	20301435[PMID]
EIF2B5	ORPHA:99853Ovarioleukodystrophy	Disease-causing germline mutation(s) in	Assessed	HGNC:3261	ENSG00000145191	603945	3q27.1	eukaryotic translation initiation factor 2B subunit epsilon	20301435[PMID]_15136673[PMID]
EIF2B5	ORPHA:99854Cree leukoencephalopathy	Disease-causing germline mutation(s) in	Assessed	HGNC:3261	ENSG00000145191	603945	3q27.1	eukaryotic translation initiation factor 2B subunit epsilon	20301435[PMID]_15136673[PMID]
EIF2B5	ORPHA:157713Congenital or early infantile CACH syndrome	Disease-causing germline mutation(s) in	Assessed	HGNC:3261	ENSG00000145191	603945	3q27.1	eukaryotic translation initiation factor 2B subunit epsilon	20301435[PMID]
EIF2B5	ORPHA:157716Late infantile CACH syndrome	Disease-causing germline mutation(s) in	Assessed	HGNC:3261	ENSG00000145191	603945	3q27.1	eukaryotic translation initiation factor 2B subunit epsilon	20301435[PMID]
EIF2B5	ORPHA:157719Juvenile or adult CACH syndrome	Disease-causing germline mutation(s) in	Assessed	HGNC:3261	ENSG00000145191	603945	3q27.1	eukaryotic translation initiation factor 2B subunit epsilon	20301435[PMID]

Prevalence and incidence

2 records

Type	Class	Value	Area	Qualification	Validation	Source
Cases/families		148 cases	Worldwide	Case(s)	Validated	ORPHANET
Point prevalence	Unknown	—	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.

HPO phenotypes

55 annotations · validated 2020-12-18

HPO	Term (as annotated by Orphanet)	Diagnostic
Very frequent (99-80%)
HP:0410263	Brain imaging abnormality
HP:0006978	Dysmyelinating leukodystrophy
Frequent (79-30%)
HP:0007366	Atrophy/Degeneration affecting the brainstem
HP:0001272	Cerebellar atrophy
HP:0006855	Cerebellar vermis atrophy
HP:0002059	Cerebral atrophy
HP:0001347	Hyperreflexia
HP:0000737	Irritability
HP:0002070	Limb ataxia
HP:0000648	Optic atrophy
HP:0008209	Premature ovarian insufficiency
HP:0002344	Progressive neurologic deterioration
HP:0001250	Seizure
HP:0001257	Spasticity
HP:0002078	Truncal ataxia
Occasional (29-5%)
HP:0007361	Abnormality of the pons
HP:0000741	Apathy
HP:0002804	Arthrogryposis multiplex congenita
HP:0000708	Atypical behavior
HP:0000618	Blindness
HP:0000518	Cataract
HP:0100543	Cognitive impairment
HP:0001558	Decreased fetal movement
HP:0001260	Dysarthria
HP:0032398	Dysgyria
HP:0001310	Dysmetria
HP:0002015	Dysphagia
HP:0001298	Encephalopathy
HP:0011968	Feeding difficulties
HP:0001371	Flexion contracture
HP:0008947	Floppy infant
HP:0033049	Globus pallidus hypointensity on susceptibility-weighted imaging
HP:0000133	Gonadal dysgenesis
HP:0001510	Growth delay
HP:0002315	Headache
HP:0001269	Hemiparesis
HP:0001433	Hepatosplenomegaly
HP:0001511	Intrauterine growth retardation
HP:0006956	Lateral ventricle dilatation
HP:0000252	Microcephaly
HP:0002076	Migraine
HP:0011342	Mild global developmental delay
HP:0001270	Motor delay
HP:0008288	Nonketotic hyperglycinemia
HP:0001562	Oligohydramnios
HP:0100653	Optic neuritis
HP:0001733	Pancreatitis
HP:0000786	Primary amenorrhea
HP:0000089	Renal hypoplasia
HP:0000869	Secondary amenorrhea
HP:0001264	Spastic diplegia
HP:0012690	T2 hypointense thalamus
HP:0002013	Vomiting
HP:0012704	Widened subarachnoid space
Very rare (<4-1%)
HP:0004481	Progressive macrocephaly

Run the differential on the 2 obligate / very frequent terms

Annotation source: 29740943[PMID]_20301435[PMID]

Sources for this card

Orphanet page: orpha.net/en/disease/detail/135
This record as JSON: /data/d/135.json