CAAHD
MCID: CNG538
MIFTS: 30

Congenital Arthrogryposis with Anterior Horn Cell Disease (CAAHD)

Categories: Fetal diseases, Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Congenital Arthrogryposis with Anterior Horn Cell Disease

MalaCards integrated aliases for Congenital Arthrogryposis with Anterior Horn Cell Disease:

Name: Congenital Arthrogryposis with Anterior Horn Cell Disease 57 74
Lethal Arthrogryposis with Anterior Horn Cell Disease 74 37 29 6
Arthrogryposis, Lethal, with Anterior Horn Cell Disease 13 40
Caahd 57 74
Laahd 59 74
Lethal Arthrogryposis with Anterior Horn Cell Disease, Formerly; Laahd, Formerly 57
Lethal Arthrogryposis with Anterior Horn Cell Disease, Formerly 57
Lethal Arthrogryposis-Anterior Horn Cell Disease Syndrome 59
Laahd, Formerly 57
Vuopala Disease 59

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
highly variable severity
onset in utero
death in infancy or early childhood may occur


HPO:

32
congenital arthrogryposis with anterior horn cell disease:
Clinical modifier neonatal death
Inheritance autosomal recessive inheritance
Onset and clinical course variable expressivity congenital onset


Classifications:



External Ids:

OMIM 57 611890
KEGG 37 H01030
UMLS via Orphanet 73 C2678471
Orphanet 59 ORPHA53696
MedGen 42 C2678471

Summaries for Congenital Arthrogryposis with Anterior Horn Cell Disease

OMIM : 57 Congenital arthrogryposis with anterior horn cell disease (CAAHD) is an autosomal recessive neuromuscular disorder with highly variable severity. Affected individuals are usually noted to have contractures in utero on prenatal ultrasound studies, and present at birth with generalized contractures manifest as arthrogryposis multiplex congenita (AMC). Patients have severe hypotonia with respiratory insufficiency, often resulting in death in infancy or early childhood. Some patients may survive into later childhood with supportive care, but may be unable to walk or sit independently due to a combination of muscle weakness and contractures. Cognition may be normal. The disorder also includes multiple congenital anomalies associated with AMC and hypotonia, including high-arched palate, myopathic facies, and bulbar weakness. Neuropathologic studies demonstrate severe loss of anterior horn cells in the spinal cord, as well as diffuse motor neuron axonopathy (summary by Smith et al., 2017 and Tan et al., 2017). (611890)

MalaCards based summary : Congenital Arthrogryposis with Anterior Horn Cell Disease, also known as lethal arthrogryposis with anterior horn cell disease, is related to fetal akinesia deformation sequence 1 and alkuraya-kucinskas syndrome. An important gene associated with Congenital Arthrogryposis with Anterior Horn Cell Disease is GLE1 (GLE1 RNA Export Mediator). Affiliated tissues include spinal cord, tongue and skeletal muscle, and related phenotypes are seizures and microcephaly

KEGG : 37
Lethal arthrogryposis with anterior horn cell disease (LAAHD) is a condition with fetal akinesia deformation sequence (FADS), multiple contractures and facial anomalies. Motor neuron loss is also present in patients with LAAHD.

UniProtKB/Swiss-Prot : 74 Congenital arthrogryposis with anterior horn cell disease: An autosomal recessive disorder characterized by fetal akinesia, arthrogryposis and motor neuron loss. The fetus often survives delivery, but dies early as a result of respiratory failure. Neuropathological findings resemble those of lethal congenital contracture syndrome type 1, but are less severe.

Related Diseases for Congenital Arthrogryposis with Anterior Horn Cell Disease

Diseases related to Congenital Arthrogryposis with Anterior Horn Cell Disease via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 fetal akinesia deformation sequence 1 10.2
2 alkuraya-kucinskas syndrome 10.2
3 anterior horn cell disease 10.2
4 muscular atrophy 10.2
5 congenital amyoplasia 10.2

Graphical network of the top 20 diseases related to Congenital Arthrogryposis with Anterior Horn Cell Disease:



Diseases related to Congenital Arthrogryposis with Anterior Horn Cell Disease

Symptoms & Phenotypes for Congenital Arthrogryposis with Anterior Horn Cell Disease

Human phenotypes related to Congenital Arthrogryposis with Anterior Horn Cell Disease:

32 (show all 39)
# Description HPO Frequency HPO Source Accession
1 seizures 32 very rare (1%) HP:0001250
2 microcephaly 32 very rare (1%) HP:0000252
3 dystonia 32 very rare (1%) HP:0001332
4 cerebral atrophy 32 very rare (1%) HP:0002059
5 low-set ears 32 HP:0000369
6 short neck 32 HP:0000470
7 high palate 32 HP:0000218
8 ptosis 32 HP:0000508
9 scoliosis 32 HP:0002650
10 kyphosis 32 HP:0002808
11 hip dysplasia 32 HP:0001385
12 prominent forehead 32 HP:0011220
13 respiratory insufficiency due to muscle weakness 32 HP:0002747
14 micrognathia 32 HP:0000347
15 skeletal muscle atrophy 32 HP:0003202
16 generalized hypotonia 32 HP:0001290
17 feeding difficulties 32 HP:0011968
18 retrognathia 32 HP:0000278
19 cryptorchidism 32 HP:0000028
20 myopia 32 HP:0000545
21 areflexia of lower limbs 32 HP:0002522
22 inability to walk 32 HP:0002540
23 arthrogryposis multiplex congenita 32 HP:0002804
24 motor delay 32 HP:0001270
25 talipes equinovarus 32 HP:0001762
26 fetal akinesia sequence 32 HP:0001989
27 downslanted palpebral fissures 32 HP:0000494
28 respiratory failure 32 HP:0002878
29 difficulty walking 32 HP:0002355
30 myopathic facies 32 HP:0002058
31 facial diplegia 32 HP:0001349
32 brisk reflexes 32 HP:0001348
33 peripheral axonal neuropathy 32 HP:0003477
34 single transverse palmar crease 32 HP:0000954
35 rocker bottom foot 32 HP:0001838
36 hand clenching 32 HP:0001188
37 mutism 32 HP:0002300
38 abnormal anterior horn cell morphology 32 HP:0006802
39 paucity of anterior horn motor neurons 32 HP:0007277

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Ears:
low-set ears

Skeletal Spine:
scoliosis
kyphosis

Head And Neck Face:
prominent forehead
micrognathia
retrognathia
myopathic facies
facial diplegia

Abdomen Gastrointestinal:
feeding difficulties
tube feeding

Neurologic Central Nervous System:
inability to walk
difficulty walking
brisk reflexes
delayed motor development
seizures (in some patients)
more
Head And Neck Mouth:
high-arched palate
tent-shaped mouth
atrophic tongue

Head And Neck Head:
microcephaly (in some patients)

Skeletal:
arthrogryposis
contractures, congenital

Prenatal Manifestations Movement:
decreased fetal movements

Head And Neck Eyes:
ptosis
myopia
downslanting palpebral fissures

Skeletal Pelvis:
hip dysplasia

Respiratory:
respiratory insufficiency due to muscle weakness
respiratory failure
mechanical ventilation

Genitourinary External Genitalia Male:
cryptorchidism

Muscle Soft Tissue:
hypotonia
muscle atrophy
loss of muscle fibers and increased fibrous tissue seen on muscle biopsy
emg indicates a neurogenic process

Skeletal Feet:
rocker-bottom feet
club feet

Skeletal Hands:
clenched hands
ulnar deviation of the fingers
single palmar crease

Neurologic Peripheral Nervous System:
areflexia of the lower limbs
axonal neuropathy

Clinical features from OMIM:

611890

Drugs & Therapeutics for Congenital Arthrogryposis with Anterior Horn Cell Disease

Search Clinical Trials , NIH Clinical Center for Congenital Arthrogryposis with Anterior Horn Cell Disease

Genetic Tests for Congenital Arthrogryposis with Anterior Horn Cell Disease

Genetic tests related to Congenital Arthrogryposis with Anterior Horn Cell Disease:

# Genetic test Affiliating Genes
1 Lethal Arthrogryposis with Anterior Horn Cell Disease 29 GLE1

Anatomical Context for Congenital Arthrogryposis with Anterior Horn Cell Disease

MalaCards organs/tissues related to Congenital Arthrogryposis with Anterior Horn Cell Disease:

41
Spinal Cord, Tongue, Skeletal Muscle

Publications for Congenital Arthrogryposis with Anterior Horn Cell Disease

Articles related to Congenital Arthrogryposis with Anterior Horn Cell Disease:

# Title Authors PMID Year
1
A homozygous I684T in GLE1 as a novel cause of arthrogryposis and motor neuron loss. 38 8 71
28657126 2018
2
Survival beyond the perinatal period expands the phenotypes caused by mutations in GLE1. 38 8 71
28884921 2017
3
Expansion of the GLE1-associated arthrogryposis multiplex congenita clinical spectrum. 8 71
27684565 2017
4
Mutations in mRNA export mediator GLE1 result in a fetal motoneuron disease. 8 71
18204449 2008
5
The importance of managing the patient and not the gene: expanded phenotype of GLE1-associated arthrogryposis. 38 8
28729373 2017
6
Lethal arthrogryposis with anterior horn cell disease. 38 8
7821908 1995
7
Deleterious mutations in the essential mRNA metabolism factor, hGle1, in amyotrophic lateral sclerosis. 38
25343993 2015
8
Insights into mRNA export-linked molecular mechanisms of human disease through a Gle1 structure-function analysis. 38
24275432 2014

Variations for Congenital Arthrogryposis with Anterior Horn Cell Disease

ClinVar genetic disease variations for Congenital Arthrogryposis with Anterior Horn Cell Disease:

6 (show all 37)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 GLE1 NM_001499.2(GLE1): c.1849G> A (p.Val617Met) single nucleotide variant Pathogenic rs121434408 9:131300337-131300337 9:128538058-128538058
2 GLE1 NM_001003722.1(GLE1): c.2051T> C (p.Ile684Thr) single nucleotide variant Pathogenic rs121434409 9:131303403-131303403 9:128541124-128541124
3 GLE1 NM_001499.2(GLE1): c.433-10A> G single nucleotide variant Pathogenic rs386833693 9:131284937-131284937 9:128522658-128522658
4 GLE1 NM_001499.2(GLE1): c.1882-2A> G single nucleotide variant Pathogenic 9:131301893-131301893 9:128539614-128539614
5 GLE1 NM_001003722.1(GLE1): c.100-7_100-3delTCTCT deletion Pathogenic
6 GLE1 NM_001003722.1(GLE1): c.2078C> T (p.Ser693Phe) single nucleotide variant Pathogenic 9:131303430-131303430 9:128541151-128541151
7 GLE1 NM_001499.2(GLE1): c.1750C> T (p.Arg584Trp) single nucleotide variant Pathogenic 9:131298737-131298737 9:128536458-128536458
8 GLE1 NM_001499.2(GLE1): c.1706G> A (p.Arg569His) single nucleotide variant Likely pathogenic rs121434407 9:131298693-131298693 9:128536414-128536414
9 GLE1 NM_001499.2(GLE1): c.823G> A (p.Asp275Asn) single nucleotide variant Conflicting interpretations of pathogenicity rs146800850 9:131286051-131286051 9:128523772-128523772
10 GLE1 NM_001499.2(GLE1): c.1641T> C (p.Tyr547=) single nucleotide variant Uncertain significance rs77053118 9:131296225-131296225 9:128533946-128533946
11 GLE1 NM_001003722.1(GLE1): c.*390C> T single nucleotide variant Uncertain significance rs886063491 9:131303839-131303839 9:128541560-128541560
12 GLE1 NM_001003722.1(GLE1): c.*933A> C single nucleotide variant Uncertain significance rs537244282 9:131304382-131304382 9:128542103-128542103
13 GLE1 NM_001499.2(GLE1): c.-108C> A single nucleotide variant Uncertain significance rs545478697 9:131266977-131266977 9:128504698-128504698
14 GLE1 NM_001499.2(GLE1): c.749C> T (p.Ala250Val) single nucleotide variant Uncertain significance rs886063489 9:131285977-131285977 9:128523698-128523698
15 GLE1 NM_001003722.1(GLE1): c.2028+15G> A single nucleotide variant Uncertain significance rs886063490 9:131302632-131302632 9:128540353-128540353
16 GLE1 NM_001003722.1(GLE1): c.*640C> T single nucleotide variant Uncertain significance rs575049150 9:131304089-131304089 9:128541810-128541810
17 GLE1 NM_001499.2(GLE1): c.-81C> T single nucleotide variant Uncertain significance rs56214514 9:131267004-131267004 9:128504725-128504725
18 GLE1 NM_001499.2(GLE1): c.54C> G (p.Asp18Glu) single nucleotide variant Uncertain significance rs549769200 9:131267138-131267138 9:128504859-128504859
19 GLE1 NM_001003722.1(GLE1): c.*111T> C single nucleotide variant Uncertain significance rs567740764 9:131303560-131303560 9:128541281-128541281
20 GLE1 NM_001499.2(GLE1): c.-84A> C single nucleotide variant Uncertain significance rs886063488 9:131267001-131267001 9:128504722-128504722
21 GLE1 NM_001499.2(GLE1): c.321+13T> G single nucleotide variant Uncertain significance rs752458769 9:131271389-131271389 9:128509110-128509110
22 GLE1 NM_001499.2(GLE1): c.679C> T (p.Arg227Cys) single nucleotide variant Uncertain significance rs146025848 9:131285907-131285907 9:128523628-128523628
23 GLE1 NM_001499.2(GLE1): c.5C> G (p.Pro2Arg) single nucleotide variant Uncertain significance rs150246404 9:131267089-131267089 9:128504810-128504810
24 GLE1 NM_001499.2(GLE1): c.1393T> A (p.Ser465Thr) single nucleotide variant Uncertain significance rs141709685 9:131295872-131295872 9:128533593-128533593
25 GLE1 NM_001499.2(GLE1): c.-51G> A single nucleotide variant Uncertain significance rs527886091 9:131267034-131267034 9:128504755-128504755
26 GLE1 NM_001499.2(GLE1): c.-45T> C single nucleotide variant Uncertain significance rs372008961 9:131267040-131267040 9:128504761-128504761
27 GLE1 NM_001499.2(GLE1): c.433-15A> C single nucleotide variant Uncertain significance rs752897261 9:131284932-131284932 9:128522653-128522653
28 GLE1 NM_001003722.1(GLE1): c.*540G> A single nucleotide variant Uncertain significance rs886063492 9:131303989-131303989 9:128541710-128541710
29 GLE1 NM_001003722.1(GLE1): c.*708T> C single nucleotide variant Uncertain significance rs886063493 9:131304157-131304157 9:128541878-128541878
30 GLE1 NM_001003722.1(GLE1): c.*782C> G single nucleotide variant Uncertain significance rs886063494 9:131304231-131304231 9:128541952-128541952
31 GLE1 NM_001003722.1(GLE1): c.*907G> C single nucleotide variant Likely benign rs55823126 9:131304356-131304356 9:128542077-128542077
32 GLE1 NM_001003722.1(GLE1): c.*1005T> C single nucleotide variant Likely benign rs4466499 9:131304454-131304454 9:128542175-128542175
33 GLE1 NM_001003722.1(GLE1): c.*387C> G single nucleotide variant Likely benign rs78624767 9:131303836-131303836 9:128541557-128541557
34 GLE1 NM_001003722.1(GLE1): c.*181C> A single nucleotide variant Likely benign rs10513496 9:131303630-131303630 9:128541351-128541351
35 GLE1 NM_001499.2(GLE1): c.1000G> A (p.Glu334Lys) single nucleotide variant Benign/Likely benign rs138310419 9:131287573-131287573 9:128525294-128525294
36 GLE1 NM_001499.2(GLE1): c.727A> G (p.Ile243Val) single nucleotide variant Benign rs2275260 9:131285955-131285955 9:128523676-128523676
37 GLE1 NM_001003722.1(GLE1): c.*73G> A single nucleotide variant Benign rs10760563 9:131303522-131303522 9:128541243-128541243

UniProtKB/Swiss-Prot genetic disease variations for Congenital Arthrogryposis with Anterior Horn Cell Disease:

74
# Symbol AA change Variation ID SNP ID
1 GLE1 p.Val617Met VAR_043876 rs121434408
2 GLE1 p.Ile684Thr VAR_043877 rs121434409

Expression for Congenital Arthrogryposis with Anterior Horn Cell Disease

Search GEO for disease gene expression data for Congenital Arthrogryposis with Anterior Horn Cell Disease.

Pathways for Congenital Arthrogryposis with Anterior Horn Cell Disease

GO Terms for Congenital Arthrogryposis with Anterior Horn Cell Disease

Sources for Congenital Arthrogryposis with Anterior Horn Cell Disease

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