CACH syndrome

General Information (adopted from Orphanet):

Synonyms, Signs: OVARIOLEUKODYSTROPHY, INCLUDED
CHILDHOOD ATAXIA WITH CENTRAL NERVOUS SYSTEM HYPOMYELINIZATION
VANISHING WHITE MATTER LEUKODYSTROPHY
CREE LEUKOENCEPHALOPATHY
CLE VANISHING WHITE MATTER LEUKODYSTROPHY WITH OVARIAN FAILURE, INCLUDED
VWM
CACH
Leukoencephalopathy with vanishing white matter
Childhood ataxia with diffuse central nervous system hypomyelination
Myelinosis centralis diffusa
Number of Symptoms 57
OrphanetNr: 135
OMIM Id: 603896
ICD-10: E75.2
UMLs: C1858991
C2931489
MeSH: C537420
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: 148 cases [Orphanet]
Inheritance: Autosomal recessive
[Orphanet]
Age of onset: Childhood
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: Leukodystrophy
 -Rare genetic disease
 -Rare neurologic disease

Symptom Information: Sort by abundance 

1
(HPO:0000869) Secondary amenorrhea 42 / 7739
2
(HPO:0008209) Premature ovarian failure 28 / 7739
3
(HPO:0004485) Cessation of head growth 1 / 7739
4
(HPO:0000256) Macrocephaly Frequent [HPO:probinson] 298 / 7739
5
(HPO:0000618) Blindness Occasional [HPO:probinson] 124 / 7739
6
(HPO:0000648) Optic atrophy 238 / 7739
7
(HPO:0002376) Developmental regression 74 / 7739
8
(HPO:0002317) Unsteady gait 45 / 7739
9
(HPO:0100543) Cognitive impairment 230 / 7739
10
(HPO:0001288) Gait disturbance 318 / 7739
11
(HPO:0000751) Personality changes 33 / 7739
12
(HPO:0000741) Apathy 42 / 7739
13
(HPO:0000712) Emotional lability 44 / 7739
14
(HPO:0001254) Lethargy 104 / 7739
15
(HPO:0002354) Memory impairment 63 / 7739
16
(HPO:0000746) Delusions 21 / 7739
17
(HPO:0001257) Spasticity 251 / 7739
18
(HPO:0001260) Dysarthria 329 / 7739
19
(HPO:0001250) Seizures 1245 / 7739
20
(HPO:0008233) Decreased serum progesterone 7 / 7739
21
(HPO:0008193) Primary gonadal insufficiency 7 / 7739
22
(HPO:0001324) Muscle weakness 859 / 7739
23
(HPO:0001252) Muscular hypotonia 990 / 7739
24
(HPO:0010547) Muscle flaccidity 466 / 7739
25
(HPO:0008947) Infantile muscular hypotonia 482 / 7739
26
(OMIM) Biopsy shows white matter hypomyelination, demyelination, gliosis 6 / 7739
27
(OMIM) Subset of patients with ovarioleukodystrophy have primary amenorrhea 6 / 7739
28
(OMIM) White matter rarefaction and cystic degeneration 6 / 7739
29
(HPO:0007305) CNS demyelination 21 / 7739
30
(OMIM) Cystic degeneration of cerebral white matter with preserved cortex 6 / 7739
31
(OMIM) Increased serum gonadotropins 6 / 7739
32
(OMIM) MRS shows decreased creatine in white matter 6 / 7739
33
(OMIM) Deterioration of motor development 6 / 7739
34
(OMIM) Chronic-progressive course with episodes of rapid deterioration following fever or head trauma 6 / 7739
35
(OMIM) MRS shows decreased choline in affected white matter 6 / 7739
36
(OMIM) MRI shows symmetric, diffuse lesions with CSF-like signal intensity 6 / 7739
37
(OMIM) Mild mental decline 6 / 7739
38
(OMIM) Rapid, instantaneous neurologic decline may occur after fright 6 / 7739
39
(OMIM) Psychiatric manifestations more common with adult-onset of disease 6 / 7739
40
(OMIM) Over time, white matter vanishes and is replaced by CSF 6 / 7739
41
(OMIM) Biopsy shows foamy lipid-laden macrophages 6 / 7739
42
(OMIM) Decreased amount of myelin-specific lipids 6 / 7739
43
(HPO:0006808) Cerebral hypomyelination 16 / 7739
44
(OMIM) Leukoencephalopathy, severe 6 / 7739
45
(OMIM) Cavitating leukoencephalopathy 7 / 7739
46
(HPO:0003621) Juvenile onset Frequent [HPO:probinson] 105 / 7739
47
(OMIM) Ovarian failure, in a subset of affected patients (ovarioleukodystrophy) 6 / 7739
48
(OMIM) Decreased amount of myelin-specific proteins 6 / 7739
49
(OMIM) Loss of coordination 6 / 7739
50
(HPO:0000007) Autosomal recessive inheritance 2538 / 7739
51
(OMIM) Developmental regression in affected children 6 / 7739
52
(OMIM) Macrocephaly may develop in those who survive past age 2 years 6 / 7739
53
(OMIM) Cessation of head growth in affected infants 6 / 7739
54
(OMIM) Magnetic resonance spectroscopy (MRS) shows decreased N-acetylaspartic acid in unaffected white matter 6 / 7739
55
(OMIM) Decreased serum estrogen 6 / 7739
56
(HPO:0002352) Leukoencephalopathy 32 / 7739
57
(OMIM) Blindness may occur in affected infants 6 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Vanishing white matter leukodystrophy is an autosomal recessive neurologic disorder characterized by variable neurologic features, including progressive cerebellar ataxia, spasticity, and cognitive impairment associated with white matter lesions on brain imaging. The age at onset can range from ...
Diagnosis OMIM Van der Knaap et al. (1998) proposed the following diagnostic criteria for vanishing white matter: (1) initial motor and mental development is normal or mildly delayed; (2) neurologic deterioration has a chronic progressive and episodic course, and episodes ...
Clinical Description OMIM Van der Knaap et al. (1997) identified 9 children with a 'new' leukoencephalopathy with vanishing white matter. The 9 patients included 3 affected sib pairs; the age range was 3 to 19 years. The onset of the disease ...
Genotype-Phenotype Correlations OMIM Fogli et al. (2004) found that 68 (87%) of 78 families with MRI criteria of leukodystrophy had a mutation in 4 of the EIF2B genes. Forty-two families (62%) had a mutation in the EIF2B5 gene, and 71% had ...
Molecular genetics OMIM By a genealogic study and haplotyping, Leegwater et al. (2001) showed that single founder was involved for 12 people with VWM in 9 families. This permitted narrowing of the location of the gene to a critical region containing ...