CHN3
MCID: NRP065
MIFTS: 24

Neuropathy, Congenital Hypomyelinating, 3 (CHN3)

Categories: Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Neuropathy, Congenital Hypomyelinating, 3

MalaCards integrated aliases for Neuropathy, Congenital Hypomyelinating, 3:

Name: Neuropathy, Congenital Hypomyelinating, 3 58 76
Chn3 58 76
Hypomyelinating Neuropathy, Congenital, 3 58
Congenital Hypomyelinating Neuropathy 3 6

Characteristics:

OMIM:

58
Inheritance:
autosomal recessive

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


HPO:

33
neuropathy, congenital hypomyelinating, 3:
Onset and clinical course congenital onset


Classifications:



Summaries for Neuropathy, Congenital Hypomyelinating, 3

UniProtKB/Swiss-Prot : 76 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 chn3. An important gene associated with Neuropathy, Congenital Hypomyelinating, 3 is CNTNAP1 (Contactin Associated Protein 1). Affiliated tissues include brain and eye, and related phenotypes are seizures and arthrogryposis multiplex congenita

OMIM : 58 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)

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:

33 (show all 24)
# Description HPO Frequency HPO Source Accession
1 seizures 33 very rare (1%) HP:0001250
2 arthrogryposis multiplex congenita 33 very rare (1%) HP:0002804
3 low-set ears 33 HP:0000369
4 high palate 33 HP:0000218
5 ptosis 33 HP:0000508
6 spasticity 33 HP:0001257
7 hyperreflexia 33 HP:0001347
8 respiratory insufficiency 33 HP:0002093
9 gingival overgrowth 33 HP:0000212
10 hearing impairment 33 HP:0000365
11 thick vermilion border 33 HP:0012471
12 microcephaly 33 HP:0000252
13 visual impairment 33 HP:0000505
14 gastroesophageal reflux 33 HP:0002020
15 micrognathia 33 HP:0000347
16 epicanthus 33 HP:0000286
17 dolichocephaly 33 HP:0000268
18 babinski sign 33 HP:0003487
19 dystonia 33 HP:0001332
20 hyporeflexia 33 HP:0001265
21 cerebellar atrophy 33 HP:0001272
22 facial diplegia 33 HP:0001349
23 hypoplasia of the corpus callosum 33 HP:0002079
24 cns hypomyelination 33 HP:0003429

Symptoms via clinical synopsis from OMIM:

58
Head And Neck Ears:
low-set ears
hearing impairment

Neurologic Central Nervous System:
spasticity
hyperreflexia
dystonia
cerebellar atrophy
hypomyelination
more
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 Hands:
clenched hands

Prenatal Manifestations Movement:
reduced fetal movement

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

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

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

Growth Other:
poor overall growth

Respiratory:
respiratory insufficiency, neonatal
ventilatory support

Skeletal Limbs:
limb contractures

Clinical features from OMIM:

618186

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

Anatomical Context for Neuropathy, Congenital Hypomyelinating, 3

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

42
Brain, Eye

Publications for Neuropathy, Congenital Hypomyelinating, 3

Articles related to Neuropathy, Congenital Hypomyelinating, 3:

# Title Authors Year
1
Phenotype of CNTNAP1: a study of patients demonstrating a specific severe congenital hypomyelinating neuropathy with survival beyond infancy. ( 29511323 )
2018
2
Balanced design for the feasible super rocket fuels: A first-principle study on gauche CHN7 and CHN3. ( 29793214 )
2018
3
Two novel variants in CNTNAP1 in two siblings presenting with congenital hypotonia and hypomyelinating neuropathy. ( 27782105 )
2017
4
CNTNAP1 mutations cause CNS hypomyelination and neuropathy with or without arthrogryposis. ( 28374019 )
2017
5
Novel mutation in CNTNAP1 results in congenital hypomyelinating neuropathy. ( 27668699 )
2017
6
Contactin-Associated Protein 1 (CNTNAP1) Mutations Induce Characteristic Lesions of the Paranodal Region. ( 27818385 )
2016

Variations for Neuropathy, Congenital Hypomyelinating, 3

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

6 (show all 14)
# Gene Variation Type Significance SNP ID Assembly Location
1 CNTNAP1 NM_003632.2(CNTNAP1): c.1869G> A (p.Trp623Ter) single nucleotide variant Pathogenic rs878853221 GRCh38 Chromosome 17, 42690752: 42690752
2 CNTNAP1 NM_003632.2(CNTNAP1): c.1869G> A (p.Trp623Ter) single nucleotide variant Pathogenic rs878853221 GRCh37 Chromosome 17, 40842770: 40842770
3 CNTNAP1 NM_003632.2(CNTNAP1): c.967T> C (p.Cys323Arg) single nucleotide variant Pathogenic rs768554986 GRCh38 Chromosome 17, 42686969: 42686969
4 CNTNAP1 NM_003632.2(CNTNAP1): c.967T> C (p.Cys323Arg) single nucleotide variant Pathogenic rs768554986 GRCh37 Chromosome 17, 40838987: 40838987
5 CNTNAP1 NM_003632.2(CNTNAP1): c.1163G> C (p.Arg388Pro) single nucleotide variant Likely pathogenic rs779027563 GRCh37 Chromosome 17, 40839856: 40839856
6 CNTNAP1 NM_003632.2(CNTNAP1): c.1163G> C (p.Arg388Pro) single nucleotide variant Likely pathogenic rs779027563 GRCh38 Chromosome 17, 42687838: 42687838
7 CNTNAP1 NM_003632.3(CNTNAP1): c.635T> C (p.Leu212Pro) single nucleotide variant Pathogenic GRCh37 Chromosome 17, 40837358: 40837358
8 CNTNAP1 NM_003632.3(CNTNAP1): c.635T> C (p.Leu212Pro) single nucleotide variant Pathogenic GRCh38 Chromosome 17, 42685340: 42685340
9 CNTNAP1 NM_003632.3(CNTNAP1): c.2011C> T (p.Gln671Ter) single nucleotide variant Pathogenic GRCh38 Chromosome 17, 42690894: 42690894
10 CNTNAP1 NM_003632.3(CNTNAP1): c.2011C> T (p.Gln671Ter) single nucleotide variant Pathogenic GRCh37 Chromosome 17, 40842912: 40842912
11 CNTNAP1 NM_003632.3(CNTNAP1): c.2290C> T (p.Arg764Cys) single nucleotide variant Pathogenic GRCh37 Chromosome 17, 40843475: 40843475
12 CNTNAP1 NM_003632.3(CNTNAP1): c.2290C> T (p.Arg764Cys) single nucleotide variant Pathogenic GRCh38 Chromosome 17, 42691457: 42691457
13 CNTNAP1 NM_003632.3(CNTNAP1): c.1677G> A (p.Trp559Ter) single nucleotide variant Pathogenic GRCh37 Chromosome 17, 40841587: 40841587
14 CNTNAP1 NM_003632.3(CNTNAP1): c.1677G> A (p.Trp559Ter) single nucleotide variant Pathogenic GRCh38 Chromosome 17, 42689569: 42689569

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

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