CAAHD
MCID: CNG538
MIFTS: 32

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 56 73 36
Lethal Arthrogryposis with Anterior Horn Cell Disease 73 29 6
Arthrogryposis, Lethal, with Anterior Horn Cell Disease 13 39
Caahd 56 73
Lethal Arthrogryposis with Anterior Horn Cell Disease, Formerly; Laahd, Formerly 56
Lethal Arthrogryposis with Anterior Horn Cell Disease, Formerly 56
Arthrogryposis-Anterior Horn Cell Disease Syndrome 58
Laahd, Formerly 56
Vuopala Disease 58
Laahd 73
Aahd 58

Characteristics:

OMIM:

56
Inheritance:
autosomal recessive

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


HPO:

31
congenital arthrogryposis with anterior horn cell disease:
Clinical modifier neonatal death
Inheritance autosomal recessive inheritance
Onset and clinical course variable expressivity congenital onset


Classifications:

Orphanet: 58  
Developmental anomalies during embryogenesis


Summaries for Congenital Arthrogryposis with Anterior Horn Cell Disease

OMIM : 56 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, skeletal muscle and tongue, and related phenotypes are microcephaly and dystonia

KEGG : 36 Congenital arthrogryposis with anterior horn cell disease (CAAHD), formerly known as 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 CAAHD.

UniProtKB/Swiss-Prot : 73 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:

31 (show all 40)
# Description HPO Frequency HPO Source Accession
1 microcephaly 31 very rare (1%) HP:0000252
2 dystonia 31 very rare (1%) HP:0001332
3 cerebral atrophy 31 very rare (1%) HP:0002059
4 seizure 31 very rare (1%) HP:0001250
5 short neck 31 HP:0000470
6 hip dysplasia 31 HP:0001385
7 scoliosis 31 HP:0002650
8 kyphosis 31 HP:0002808
9 prominent forehead 31 HP:0011220
10 respiratory insufficiency due to muscle weakness 31 HP:0002747
11 feeding difficulties 31 HP:0011968
12 skeletal muscle atrophy 31 HP:0003202
13 cryptorchidism 31 HP:0000028
14 high palate 31 HP:0000218
15 retrognathia 31 HP:0000278
16 micrognathia 31 HP:0000347
17 low-set ears 31 HP:0000369
18 ptosis 31 HP:0000508
19 myopia 31 HP:0000545
20 motor delay 31 HP:0001270
21 talipes equinovarus 31 HP:0001762
22 fetal akinesia sequence 31 HP:0001989
23 downslanted palpebral fissures 31 HP:0000494
24 dysarthria 31 HP:0001260
25 arthrogryposis multiplex congenita 31 HP:0002804
26 respiratory failure 31 HP:0002878
27 single transverse palmar crease 31 HP:0000954
28 rocker bottom foot 31 HP:0001838
29 hand clenching 31 HP:0001188
30 generalized hypotonia 31 HP:0001290
31 difficulty walking 31 HP:0002355
32 inability to walk 31 HP:0002540
33 brisk reflexes 31 HP:0001348
34 mutism 31 HP:0002300
35 peripheral axonal neuropathy 31 HP:0003477
36 myopathic facies 31 HP:0002058
37 areflexia of lower limbs 31 HP:0002522
38 facial diplegia 31 HP:0001349
39 paucity of anterior horn motor neurons 31 HP:0007277
40 abnormal anterior horn cell morphology 31 HP:0006802

Symptoms via clinical synopsis from OMIM:

56
Skeletal Pelvis:
hip dysplasia

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

Abdomen Gastrointestinal:
feeding difficulties
tube feeding

Head And Neck Ears:
low-set ears

Neurologic Central Nervous System:
difficulty walking
inability to walk
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

Skeletal Spine:
scoliosis
kyphosis

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

Genitourinary External Genitalia Male:
cryptorchidism

Head And Neck Eyes:
ptosis
myopia
downslanting palpebral fissures

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:
club feet
rocker-bottom 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

Anatomical Context for Congenital Arthrogryposis with Anterior Horn Cell Disease

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

40
Spinal Cord, Skeletal Muscle, Tongue

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. 61 6 56
28657126 2018
2
Survival beyond the perinatal period expands the phenotypes caused by mutations in GLE1. 6 56 61
28884921 2017
3
Expansion of the GLE1-associated arthrogryposis multiplex congenita clinical spectrum. 56 6
27684565 2017
4
Mutations in mRNA export mediator GLE1 result in a fetal motoneuron disease. 56 6
18204449 2008
5
The importance of managing the patient and not the gene: expanded phenotype of GLE1-associated arthrogryposis. 56 61
28729373 2017
6
Lethal arthrogryposis with anterior horn cell disease. 61 56
7821908 1995
7
Extension of the phenotypic spectrum of GLE1-related disorders to a mild congenital form resembling congenital myopathy. 61
32537934 2020
8
Deleterious mutations in the essential mRNA metabolism factor, hGle1, in amyotrophic lateral sclerosis. 61
25343993 2015
9
Insights into mRNA export-linked molecular mechanisms of human disease through a Gle1 structure-function analysis. 61
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 top 50) (show all 65) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 GLE1 NM_001499.2(GLE1):c.1882-2A>GSNV Pathogenic 619141 rs1336481358 9:131301893-131301893 9:128539614-128539614
2 GLE1 NM_001003722.1(GLE1):c.100-7_100-3deldeletion Pathogenic 619142 9:131271147-131271151 9:128508868-128508872
3 GLE1 NM_001003722.1(GLE1):c.2078C>T (p.Ser693Phe)SNV Pathogenic 619143 rs1564162129 9:131303430-131303430 9:128541151-128541151
4 GLE1 NM_001499.2(GLE1):c.1750C>T (p.Arg584Trp)SNV Pathogenic 619144 rs765269946 9:131298737-131298737 9:128536458-128536458
5 GLE1 NM_001499.2(GLE1):c.1849G>A (p.Val617Met)SNV Pathogenic 6464 rs121434408 9:131300337-131300337 9:128538058-128538058
6 GLE1 NM_001003722.1(GLE1):c.2051T>C (p.Ile684Thr)SNV Pathogenic 6465 rs121434409 9:131303403-131303403 9:128541124-128541124
7 GLE1 NM_001499.2(GLE1):c.433-10A>GSNV Pathogenic 6462 rs386833693 9:131284937-131284937 9:128522658-128522658
8 GLE1 NM_001499.2(GLE1):c.1706G>A (p.Arg569His)SNV Likely pathogenic 6463 rs121434407 9:131298693-131298693 9:128536414-128536414
9 GLE1 NM_001499.2(GLE1):c.823G>A (p.Asp275Asn)SNV Conflicting interpretations of pathogenicity 256860 rs146800850 9:131286051-131286051 9:128523772-128523772
10 GLE1 NM_001499.2(GLE1):c.1393T>A (p.Ser465Thr)SNV Conflicting interpretations of pathogenicity 289027 rs141709685 9:131295872-131295872 9:128533593-128533593
11 GLE1 NM_001499.2(GLE1):c.1641T>C (p.Tyr547=)SNV Conflicting interpretations of pathogenicity 193820 rs77053118 9:131296225-131296225 9:128533946-128533946
12 GLE1 NM_001003722.2(GLE1):c.643-4A>GSNV Conflicting interpretations of pathogenicity 706615 9:131285867-131285867 9:128523588-128523588
13 GLE1 NM_001003722.2(GLE1):c.1243-5G>ASNV Conflicting interpretations of pathogenicity 706479 9:131289730-131289730 9:128527451-128527451
14 GLE1 NM_001003722.2(GLE1):c.-34G>ASNV Uncertain significance 912454 9:131267051-131267051 9:128504772-128504772
15 GLE1 NM_001003722.2(GLE1):c.76C>G (p.Arg26Gly)SNV Uncertain significance 913573 9:131267160-131267160 9:128504881-128504881
16 GLE1 NM_001003722.2(GLE1):c.485C>T (p.Ser162Leu)SNV Uncertain significance 913956 9:131284999-131284999 9:128522720-128522720
17 GLE1 NM_001003722.2(GLE1):c.573G>C (p.Met191Ile)SNV Uncertain significance 913957 9:131285087-131285087 9:128522808-128522808
18 GLE1 NM_001003722.2(GLE1):c.719A>G (p.Glu240Gly)SNV Uncertain significance 915198 9:131285947-131285947 9:128523668-128523668
19 GLE1 NM_001003722.2(GLE1):c.737G>A (p.Arg246Gln)SNV Uncertain significance 915199 9:131285965-131285965 9:128523686-128523686
20 GLE1 NM_001003722.2(GLE1):c.928G>A (p.Glu310Lys)SNV Uncertain significance 912487 9:131287501-131287501 9:128525222-128525222
21 GLE1 NM_001003722.2(GLE1):c.947G>A (p.Arg316Gln)SNV Uncertain significance 912488 9:131287520-131287520 9:128525241-128525241
22 GLE1 NM_001003722.2(GLE1):c.1109C>T (p.Pro370Leu)SNV Uncertain significance 913605 9:131287682-131287682 9:128525403-128525403
23 GLE1 NM_001003722.2(GLE1):c.1396G>A (p.Val466Ile)SNV Uncertain significance 914004 9:131295875-131295875 9:128533596-128533596
24 GLE1 NM_001003722.2(GLE1):c.1431A>G (p.Gln477=)SNV Uncertain significance 914005 9:131295910-131295910 9:128533631-128533631
25 GLE1 NM_001003722.2(GLE1):c.1493C>G (p.Ala498Gly)SNV Uncertain significance 914006 9:131296077-131296077 9:128533798-128533798
26 GLE1 NM_001003722.2(GLE1):c.1554C>A (p.Asp518Glu)SNV Uncertain significance 914007 9:131296138-131296138 9:128533859-128533859
27 GLE1 NM_001003722.2(GLE1):c.*381C>TSNV Uncertain significance 912543 9:131303830-131303830 9:128541551-128541551
28 GLE1 NM_001003722.2(GLE1):c.*425A>GSNV Uncertain significance 913645 9:131303874-131303874 9:128541595-128541595
29 GLE1 NM_001003722.2(GLE1):c.*525C>TSNV Uncertain significance 913646 9:131303974-131303974 9:128541695-128541695
30 GLE1 NM_001003722.2(GLE1):c.*536G>ASNV Uncertain significance 914048 9:131303985-131303985 9:128541706-128541706
31 GLE1 NM_001003722.2(GLE1):c.*599G>ASNV Uncertain significance 914049 9:131304048-131304048 9:128541769-128541769
32 GLE1 NM_001003722.2(GLE1):c.*618T>CSNV Uncertain significance 914050 9:131304067-131304067 9:128541788-128541788
33 GLE1 NM_001003722.2(GLE1):c.*907G>ASNV Uncertain significance 914557 9:131304356-131304356 9:128542077-128542077
34 GLE1 NM_001003722.2(GLE1):c.*962C>TSNV Uncertain significance 912589 9:131304411-131304411 9:128542132-128542132
35 GLE1 NM_001003722.2(GLE1):c.*1002G>CSNV Uncertain significance 912590 9:131304451-131304451 9:128542172-128542172
36 GLE1 NM_001003722.2(GLE1):c.1130-15T>CSNV Uncertain significance 913606 9:131289443-131289443 9:128527164-128527164
37 GLE1 NM_001003722.2(GLE1):c.1882-8C>GSNV Uncertain significance 915237 9:131301887-131301887 9:128539608-128539608
38 GLE1 NM_001003722.2(GLE1):c.1964+8G>TSNV Uncertain significance 915238 9:131301985-131301985 9:128539706-128539706
39 GLE1 NM_001499.2(GLE1):c.-51G>ASNV Uncertain significance 365129 rs527886091 9:131267034-131267034 9:128504755-128504755
40 GLE1 NM_001499.2(GLE1):c.-45T>CSNV Uncertain significance 365130 rs372008961 9:131267040-131267040 9:128504761-128504761
41 GLE1 NM_001003722.1(GLE1):c.*390C>TSNV Uncertain significance 365140 rs886063491 9:131303839-131303839 9:128541560-128541560
42 GLE1 NM_001003722.1(GLE1):c.*933A>CSNV Uncertain significance 365146 rs537244282 9:131304382-131304382 9:128542103-128542103
43 GLE1 NM_001499.2(GLE1):c.-108C>ASNV Uncertain significance 365126 rs545478697 9:131266977-131266977 9:128504698-128504698
44 GLE1 NM_001499.2(GLE1):c.749C>T (p.Ala250Val)SNV Uncertain significance 365134 rs886063489 9:131285977-131285977 9:128523698-128523698
45 GLE1 NM_001003722.1(GLE1):c.2028+15G>ASNV Uncertain significance 365135 rs886063490 9:131302632-131302632 9:128540353-128540353
46 GLE1 NM_001003722.1(GLE1):c.*640C>TSNV Uncertain significance 365142 rs575049150 9:131304089-131304089 9:128541810-128541810
47 GLE1 NM_001499.2(GLE1):c.-81C>TSNV Uncertain significance 365128 rs56214514 9:131267004-131267004 9:128504725-128504725
48 GLE1 NM_001499.2(GLE1):c.54C>G (p.Asp18Glu)SNV Uncertain significance 365131 rs549769200 9:131267138-131267138 9:128504859-128504859
49 GLE1 NM_001003722.1(GLE1):c.*111T>CSNV Uncertain significance 365137 rs567740764 9:131303560-131303560 9:128541281-128541281
50 GLE1 NM_001499.2(GLE1):c.-84A>CSNV Uncertain significance 365127 rs886063488 9:131267001-131267001 9:128504722-128504722

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

73
# 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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