Congenital or early infantile 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
Number of Symptoms 47
OrphanetNr: 157713
OMIM Id: 603896
ICD-10: E75.2
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal recessive inheritance
[Omim]
Age of onset: Juvenile onset
[Omim]

Disease classification (adopted from Orphanet):

Parent Diseases: CACH syndrome
 -Rare genetic disease
 -Rare neurologic disease

Symptom Information: Sort by abundance 

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