CHN3
MCID: NRP065
MIFTS: 27

Neuropathy, Congenital Hypomyelinating, 3 (CHN3)

Categories: Genetic diseases, Muscle diseases, Neuronal diseases, Rare diseases, Respiratory diseases

Aliases & Classifications for Neuropathy, Congenital Hypomyelinating, 3

MalaCards integrated aliases for Neuropathy, Congenital Hypomyelinating, 3:

Name: Neuropathy, Congenital Hypomyelinating, 3 57 72
Congenital Hypomyelinating Neuropathy 3 29 6
Chn3 57 72
Hypomyelinating Neuropathy, Congenital, 3 57

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive

Miscellaneous:
onset in utero
some patients die in infancy or early childhood


HPO:

31
neuropathy, congenital hypomyelinating, 3:
Inheritance autosomal recessive inheritance
Onset and clinical course congenital onset


Classifications:



Summaries for Neuropathy, Congenital Hypomyelinating, 3

UniProtKB/Swiss-Prot : 72 Neuropathy, congenital hypomyelinating, 3: A form of congenital hypomyelinating neuropathy, a neurologic disorder characterized by early-onset hypotonia, areflexia, distal muscle weakness, and very slow nerve conduction velocities (NCV) resulting from improper myelination of axons. In its extreme form, it may present with severe joint contractures or arthrogryposis multiplex congenita and respiratory insufficiency. In less severe cases patients may achieve walking. Patients lack both active myelin breakdown and well-organized onion bulbs on sural nerve biopsies, have absence of inflammation, and show hypomyelination of most or all fibers. CHN3 is a severe autosomal recessive form characterized by onset of neurogenic muscle impairment in utero. Affected individuals have profoundly impaired psychomotor development and may die in infancy or early childhood.

MalaCards based summary : Neuropathy, Congenital Hypomyelinating, 3, is also known as congenital hypomyelinating neuropathy 3. An important gene associated with Neuropathy, Congenital Hypomyelinating, 3 is CNTNAP1 (Contactin Associated Protein 1). Affiliated tissues include eye, and related phenotypes are arthrogryposis multiplex congenita and seizure

OMIM® : 57 Congenital hypomyelinating neuropathy-3 is an autosomal recessive neurologic disorder characterized by onset of neurogenic muscle impairment in utero. Affected individuals present at birth with severe hypotonia, often causing respiratory insufficiency or failure and inability to swallow or feed properly. They have profoundly impaired psychomotor development and may die in infancy or early childhood. Those that survive are unable to sit or walk. Sural nerve biopsy shows hypomyelination of the nerve fibers, and brain imaging often shows impaired myelination and cerebral and cerebellar atrophy. Nerve conduction velocities are severely decreased (about 10 m/s) or absent due to improper myelination (summary by Vallat et al., 2016 and Low et al., 2018). For a discussion of genetic heterogeneity of CHN, see CHN1 (605253). (618186) (Updated 05-Apr-2021)

Related Diseases for Neuropathy, Congenital Hypomyelinating, 3

Diseases in the Neuropathy, Congenital Hypomyelinating, 1, Autosomal Recessive family:

Neuropathy, Congenital Hypomyelinating, 2 Neuropathy, Congenital Hypomyelinating, 3

Symptoms & Phenotypes for Neuropathy, Congenital Hypomyelinating, 3

Human phenotypes related to Neuropathy, Congenital Hypomyelinating, 3:

31 (show all 30)
# Description HPO Frequency HPO Source Accession
1 arthrogryposis multiplex congenita 31 very rare (1%) HP:0002804
2 seizure 31 very rare (1%) HP:0001250
3 spasticity 31 HP:0001257
4 hyperreflexia 31 HP:0001347
5 ptosis 31 HP:0000508
6 high palate 31 HP:0000218
7 respiratory insufficiency 31 HP:0002093
8 hearing impairment 31 HP:0000365
9 gingival overgrowth 31 HP:0000212
10 thick vermilion border 31 HP:0012471
11 microcephaly 31 HP:0000252
12 visual impairment 31 HP:0000505
13 gastroesophageal reflux 31 HP:0002020
14 micrognathia 31 HP:0000347
15 low-set ears 31 HP:0000369
16 epicanthus 31 HP:0000286
17 dolichocephaly 31 HP:0000268
18 cachexia 31 HP:0004326
19 polyhydramnios 31 HP:0001561
20 decreased fetal movement 31 HP:0001558
21 dystonia 31 HP:0001332
22 hyporeflexia 31 HP:0001265
23 babinski sign 31 HP:0003487
24 hypoplasia of the corpus callosum 31 HP:0002079
25 cerebellar atrophy 31 HP:0001272
26 hand clenching 31 HP:0001188
27 cns hypomyelination 31 HP:0003429
28 facial diplegia 31 HP:0001349
29 limb joint contracture 31 HP:0003121
30 abnormal foot morphology 31 HP:0001760

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
spasticity
hyperreflexia
dystonia
cerebellar atrophy
hypomyelination
more
Head And Neck Ears:
hearing impairment
low-set ears

Abdomen Gastrointestinal:
gastroesophageal reflux
poor or absent swallowing due to hypotonia
tube-feeding

Growth Weight:
cachexia

Neurologic Peripheral Nervous System:
hyporeflexia
thin myelin sheaths
hypomyelination seen on sural nerve biopsy
widening of the nodes of ranvier and paranodal junctional gaps
atypical onion bulb formation by the basal lamina
more
Skeletal Feet:
foot deformities

Skeletal:
joint contractures (in some patients)
arthrogryposis multiplex congenita (amc) (in some patients)

Prenatal Manifestations Movement:
reduced fetal movement

Skeletal Limbs:
limb contractures

Head And Neck Nose:
thick nares

Head And Neck Eyes:
ptosis
visual impairment
epicanthal folds
absent eye contact

Head And Neck Head:
microcephaly
dolichocephaly

Head And Neck Face:
micrognathia
facial diplegia

Prenatal Manifestations Amniotic Fluid:
polyhydramnios

Head And Neck Mouth:
high-arched palate
thick lips
gingival hypertrophy

Growth Other:
poor overall growth

Skeletal Hands:
clenched hands

Respiratory:
respiratory insufficiency, neonatal
ventilatory support

Muscle Soft Tissue:
hypotonia, profound
neurogenic atrophy see on muscle biopsy
muscle denervation seen on emg

Clinical features from OMIM®:

618186 (Updated 05-Apr-2021)

Drugs & Therapeutics for Neuropathy, Congenital Hypomyelinating, 3

Search Clinical Trials , NIH Clinical Center for Neuropathy, Congenital Hypomyelinating, 3

Genetic Tests for Neuropathy, Congenital Hypomyelinating, 3

Genetic tests related to Neuropathy, Congenital Hypomyelinating, 3:

# Genetic test Affiliating Genes
1 Congenital Hypomyelinating Neuropathy 3 29 CNTNAP1

Anatomical Context for Neuropathy, Congenital Hypomyelinating, 3

MalaCards organs/tissues related to Neuropathy, Congenital Hypomyelinating, 3:

40
Eye

Publications for Neuropathy, Congenital Hypomyelinating, 3

Articles related to Neuropathy, Congenital Hypomyelinating, 3:

(show all 12)
# Title Authors PMID Year
1
Phenotype of CNTNAP1: a study of patients demonstrating a specific severe congenital hypomyelinating neuropathy with survival beyond infancy. 6 57
29511323 2018
2
Novel mutation in CNTNAP1 results in congenital hypomyelinating neuropathy. 57 6
27668699 2017
3
CNTNAP1 mutations cause CNS hypomyelination and neuropathy with or without arthrogryposis. 6 57
28374019 2017
4
Two novel variants in CNTNAP1 in two siblings presenting with congenital hypotonia and hypomyelinating neuropathy. 57 6
27782105 2017
5
Contactin-Associated Protein 1 (CNTNAP1) Mutations Induce Characteristic Lesions of the Paranodal Region. 6 57
27818385 2016
6
First-line exome sequencing in Palestinian and Israeli Arabs with neurological disorders is efficient and facilitates disease gene discovery. 6
32214227 2020
7
Variability in the Viral Protein Linked to the Genome of Turnip Mosaic Virus Influences Interactions with eIF(iso)4Es in Brassica rapa. 61
33551696 2021
8
CNTNAP1 Mutations and Their Clinical Presentations: New Case Report and Systematic Review. 61
32328110 2020
9
Genetic characteristics of Bacillus anthracis isolated from northwestern China from 1990 to 2016. 61
30418972 2018
10
Balanced design for the feasible super rocket fuels: A first-principle study on gauche CHN7 and CHN3. 61
29793214 2018
11
Biology and management of sugarcane yellow leaf virus: an historical overview. 61
26424197 2015
12
Genome characterization of sugarcane yellow leaf virus from China reveals a novel recombinant genotype. 61
24395076 2014

Variations for Neuropathy, Congenital Hypomyelinating, 3

ClinVar genetic disease variations for Neuropathy, Congenital Hypomyelinating, 3:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 CNTNAP1 NM_003632.3(CNTNAP1):c.635T>C (p.Leu212Pro) SNV Pathogenic 590912 rs1567969825 GRCh37: 17:40837358-40837358
GRCh38: 17:42685340-42685340
2 CNTNAP1 NM_003632.3(CNTNAP1):c.2011C>T (p.Gln671Ter) SNV Pathogenic 590913 rs1567973088 GRCh37: 17:40842912-40842912
GRCh38: 17:42690894-42690894
3 CNTNAP1 NM_003632.3(CNTNAP1):c.2290C>T (p.Arg764Cys) SNV Pathogenic 590914 rs761805324 GRCh37: 17:40843475-40843475
GRCh38: 17:42691457-42691457
4 CNTNAP1 NM_003632.3(CNTNAP1):c.1677G>A (p.Trp559Ter) SNV Pathogenic 590918 rs756896276 GRCh37: 17:40841587-40841587
GRCh38: 17:42689569-42689569
5 CNTNAP1 NM_003632.3(CNTNAP1):c.967T>C (p.Cys323Arg) SNV Pathogenic 242386 rs768554986 GRCh37: 17:40838987-40838987
GRCh38: 17:42686969-42686969
6 CNTNAP1 NM_003632.3(CNTNAP1):c.1869G>A (p.Trp623Ter) SNV Pathogenic 242387 rs878853221 GRCh37: 17:40842770-40842770
GRCh38: 17:42690752-42690752
7 CNTNAP1 NM_003632.3(CNTNAP1):c.1163G>C (p.Arg388Pro) SNV Pathogenic 522842 rs779027563 GRCh37: 17:40839856-40839856
GRCh38: 17:42687838-42687838
8 CNTNAP1 NM_003632.3(CNTNAP1):c.2015G>A (p.Trp672Ter) SNV Pathogenic 560980 rs1567973091 GRCh37: 17:40842916-40842916
GRCh38: 17:42690898-42690898
9 CNTNAP1 NM_003632.3(CNTNAP1):c.151A>C (p.Arg51=) SNV Benign 803394 rs2271029 GRCh37: 17:40835922-40835922
GRCh38: 17:42683904-42683904

UniProtKB/Swiss-Prot genetic disease variations for Neuropathy, Congenital Hypomyelinating, 3:

72
# Symbol AA change Variation ID SNP ID
1 CNTNAP1 p.Arg388Pro VAR_078819 rs779027563
2 CNTNAP1 p.Arg764Cys VAR_078823 rs761805324
3 CNTNAP1 p.Pro50Gln VAR_081766
4 CNTNAP1 p.Leu212Pro VAR_081767 rs156796982
5 CNTNAP1 p.Arg714Pro VAR_081770

Expression for Neuropathy, Congenital Hypomyelinating, 3

Search GEO for disease gene expression data for Neuropathy, Congenital Hypomyelinating, 3.

Pathways for Neuropathy, Congenital Hypomyelinating, 3

GO Terms for Neuropathy, Congenital Hypomyelinating, 3

Sources for Neuropathy, Congenital Hypomyelinating, 3

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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