Neurodegeneration with brain iron accumulation due to C19orf12 mutation

General Information (adopted from Orphanet):

Synonyms, Signs: MITOCHONDRIAL PROTEIN-ASSOCIATED NEURODEGENERATION
NBIA4
NBIA5
MPAN
NBIA due to C19orf12 mutation
Neurodegeneration with brain iron accumulation type 5
Mitochondrial membrane protein associated neurodegeneration
Number of Symptoms 71
OrphanetNr: 289560
OMIM Id: 614298
ICD-10: G23.0
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance:
Age of onset:

Disease classification (adopted from Orphanet):

Parent Diseases: Autosomal recessive syndromic optic atrophy
 -Rare eye disease
 -Rare genetic disease
Neurodegeneration with brain iron accumulation
 -Rare genetic disease
 -Rare neurologic disease

Comment:

Disease severity of NBIA4 seemingly follows a genotype–phenotype relation, with homozygous frameshift or nonsense mutations leading to an earlier manifestation and more rapid progression than those with missense mutations (PMID:23521069).

Symptom Information: Sort by abundance 

1
 (HPO:0000020) Urinary incontinence 23269600 IBIS 75 / 7739
2
 (HPO:0000338) Hypomimic face 23521069 IBIS 8 / 7739
3
 (HPO:0000648) Optic atrophy Frequent [IBIS] 74% (n=23) 23269600 IBIS 238 / 7739
4
 (HPO:0000571) Hypometric saccades 23269600 IBIS 10 / 7739
5
 (HPO:0000529) Progressive visual loss 22508347 IBIS 54 / 7739
6
 (HPO:0000640) Gaze-evoked nystagmus 23269600 IBIS 27 / 7739
7
 (HPO:0007772) Impaired smooth pursuit 23269600 IBIS 21 / 7739
8
 (HPO:0000551) Abnormality of color vision 23269600 IBIS 20 / 7739
9
 (HPO:0001315) Reduced tendon reflexes 23269600 IBIS 160 / 7739
10
 (HPO:0000722) Obsessive-compulsive behavior 21981780 IBIS 35 / 7739
11
 (HPO:0007002) Motor axonal neuropathy Frequent [IBIS] 44% (n=18) 21981780 IBIS 17 / 7739
12
 (HPO:0001265) Hyporeflexia 22584950 IBIS 208 / 7739
13
 (HPO:0002015) Dysphagia Frequent [IBIS] 52% (n=21) 23269600 IBIS 301 / 7739
14
 (HPO:0000712) Emotional lability 21981780 IBIS 44 / 7739
15
 (HPO:0000726) Dementia 23269600 IBIS 131 / 7739
16
 (HPO:0001284) Areflexia 23269600 IBIS 198 / 7739
17
 (HPO:0001263) Global developmental delay 22584950 IBIS 853 / 7739
18
 (HPO:0002366) Abnormal lower motor neuron morphology 23269600 IBIS 12 / 7739
19
 (HPO:0100710) Impulsivity 21981780 IBIS 16 / 7739
20
 (HPO:0002067) Bradykinesia 23521069 IBIS 62 / 7739
21
 (HPO:0001251) Ataxia 21981780 IBIS 413 / 7739
22
 (HPO:0001300) Parkinsonism Frequent [IBIS] 72% (n=18) 21981780 IBIS 75 / 7739
23
 (HPO:0001288) Gait disturbance Frequent [IBIS] 73% (n=23) 23269600 IBIS 318 / 7739
24
 (HPO:0001268) Mental deterioration 21981780 IBIS 88 / 7739
25
 (HPO:0100543) Cognitive impairment 23269600 IBIS 230 / 7739
26
 (HPO:0001249) Intellectual disability 22584950 IBIS 1089 / 7739
27
 (HPO:0007256) Abnormal pyramidal signs 22584950 IBIS 116 / 7739
28
 (HPO:0002071) Abnormality of extrapyramidal motor function 23521069 IBIS 76 / 7739
29
 (HPO:0001347) Hyperreflexia Frequent [IBIS] 78% (n=18) 21981780 IBIS 363 / 7739
30
 (HPO:0001260) Dysarthria Very frequent [IBIS] 90% (n=21) 23269600 IBIS 329 / 7739
31
 (HPO:0001257) Spasticity Frequent [IBIS] 78% (n=18) 21981780 IBIS 251 / 7739
32
 (HPO:0001285) Spastic tetraparesis 21981780 IBIS 29 / 7739
33
 (HPO:0003487) Babinski sign Frequent [IBIS] 78% (n=18) 21981780 IBIS 179 / 7739
34
 (HPO:0001337) Tremor 21981780 IBIS 200 / 7739
35
 (HPO:0002127) Abnormal upper motor neuron morphology 23269600 IBIS 15 / 7739
36
 (HPO:0012048) Oromandibular dystonia Frequent [IBIS] 72% (n=18) 21981780 IBIS 7 / 7739
37
 (HPO:0007325) Generalized dystonia Frequent [IBIS] 72% (n=18) 21981780 IBIS 7 / 7739
38
 (HPO:0000716) Depression 21981780 IBIS 99 / 7739
39
 (HPO:0000750) Delayed speech and language development Frequent [IBIS] 556% (n=18) 21981780 IBIS 197 / 7739
40
 (HPO:0001332) Dystonia Frequent [IBIS] 71% (n=21) 23269600 IBIS 197 / 7739
41
 (HPO:0002311) Incoordination 21981780 IBIS 84 / 7739
42
 (HPO:0001780) Abnormality of toe 22584950 IBIS 5 / 7739
43
 (HPO:0003691) Scapular winging 22584950 IBIS 51 / 7739
44
 (HPO:0001761) Pes cavus 23521069 IBIS 225 / 7739
45
 (HPO:0009130) Hand muscle atrophy 22584950 IBIS 11 / 7739
46
 (HPO:0002607) Bowel incontinence 23269600 IBIS 33 / 7739
47
 (HPO:0003236) Elevated serum creatine phosphokinase 23521069 IBIS 214 / 7739
48
 (HPO:0011727) Peroneal muscle weakness 22584950 IBIS 6 / 7739
49
 (HPO:0003693) Distal amyotrophy 22584950 IBIS 118 / 7739
50
 (HPO:0002460) Distal muscle weakness Frequent [IBIS] 86% (n=21) 23269600 IBIS 122 / 7739
51
 (OMIM) Tau-containing inclusions 21981780 IBIS 1 / 7739
52
 (OMIM) Iron accumulation in the globus pallidus and substantia nigra seen on MRI 21981780 IBIS 1 / 7739
53
 (OMIM) Alpha-synuclein-containing inclusions 21981780 IBIS 1 / 7739
54
 (HPO:0012677) Iron accumulation in globus pallidus 21981780 IBIS 1 / 7739
55
 (OMIM) Increased serum creatine kinase, mild 23521069 IBIS 2 / 7739
56
 (HPO:0012753) T2 hypointense basal ganglia Very frequent [IBIS] 100% (n=24) 21981780 IBIS 1 / 7739
57
 (OMIM) Axonal spheroids 21981780 IBIS 2 / 7739
58
 (OMIM) Lower motor neuron signs, later 23269600 IBIS 1 / 7739
59
 (OMIM) Loss of myelin in the pyramidal tracts 21981780 IBIS 1 / 7739
60
 (OMIM) Iron-containing deposits in various brain regions 21981780 IBIS 1 / 7739
61
 (OMIM) Upper motor neuron signs, early 23269600 IBIS 1 / 7739
62
 (OMIM) Reduced nerve amplitudes of peroneal nerve 22584950 IBIS 1 / 7739
63
 (MedDRA:10070246) Executive dysfunction 22584950 IBIS 6 / 7739
64
 (MedDRA:10057689) Acquired claw toe 22584950 IBIS 4 / 7739
65
 (HPO:0001272) Cerebellar atrophy 23521069 IBIS 197 / 7739
66
 (HPO:0100315) Lewy bodies 21981780 IBIS 5 / 7739
67
 (HPO:0100314) Cerebral inclusion bodies 21981780 IBIS 2 / 7739
68
 (HPO:0011400) Abnormal CNS myelination 21981780 IBIS 10 / 7739
69
 (MedDRA:10010219) Compulsions 21981780 IBIS 3 / 7739
70
 (HPO:0012678) Iron accumulation in substantia nigra 21981780 IBIS 1 / 7739
71
 (OMIM) Atrophy of the small muscles in the hand 22584950 IBIS 1 / 7739

Associated genes:

C19orf12;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Neurodegeneration with brain iron accumulation-4 (NBIA4) is an autosomal recessive neurodegenerative disorder characterized by progressive spastic paraplegia, parkinsonism unresponsive to L-DOPA treatment, and psychiatric or behavioral symptoms. Other neurologic features, including optic atrophy, eye movement abnormalities, dystonia, dysphagia, ...
Clinical Description OMIM Hartig et al. (2011) reported 24 Polish patients with neurodegeneration with brain iron accumulation, including 9 patients from 4 families with 2 or 3 affected sibs. The diagnosis was based on hypointensity in the globus pallidus documented by ...
Molecular genetics OMIM In 24 Polish patients with NBIA4, Hartig et al. (2011) identified homozygous or compound heterozygous mutations in the C19ORF12 gene (see, e.g., 614297.0001-614297.0004). Eighteen patients carried the same 11-bp deletion (614297.0001), and haplotype analysis indicated a founder effect. ...