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
Lethal Arthrogryposis with Anterior Horn Cell Disease 73 36 29 6
Arthrogryposis, Lethal, with Anterior Horn Cell Disease 13 39
Caahd 56 73
Laahd 58 73
Lethal Arthrogryposis with Anterior Horn Cell Disease, Formerly; Laahd, Formerly 56
Lethal Arthrogryposis with Anterior Horn Cell Disease, Formerly 56
Lethal Arthrogryposis-Anterior Horn Cell Disease Syndrome 58
Laahd, Formerly 56
Vuopala Disease 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 alkuraya-kucinskas syndrome and anterior horn cell disease. 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 seizures and microcephaly

KEGG : 36 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 : 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 alkuraya-kucinskas syndrome 10.2
2 anterior horn cell disease 10.2
3 muscular atrophy 10.2
4 congenital amyoplasia 10.2

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

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Ears:
low-set ears

Skeletal Spine:
scoliosis
kyphosis

Abdomen Gastrointestinal:
feeding difficulties
tube feeding

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

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

Genitourinary External Genitalia Male:
cryptorchidism

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

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:

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 56 6
28657126 2018
2
Survival beyond the perinatal period expands the phenotypes caused by mutations in GLE1. 61 56 6
28884921 2017
3
Expansion of the GLE1-associated arthrogryposis multiplex congenita clinical spectrum. 6 56
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
Deleterious mutations in the essential mRNA metabolism factor, hGle1, in amyotrophic lateral sclerosis. 61
25343993 2015
8
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 all 37) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 GLE1 NM_001499.2(GLE1):c.1849G>A (p.Val617Met)SNV Pathogenic 6464 rs121434408 9:131300337-131300337 9:128538058-128538058
2 GLE1 NM_001003722.1(GLE1):c.2051T>C (p.Ile684Thr)SNV Pathogenic 6465 rs121434409 9:131303403-131303403 9:128541124-128541124
3 GLE1 NM_001499.2(GLE1):c.433-10A>GSNV Pathogenic 6462 rs386833693 9:131284937-131284937 9:128522658-128522658
4 GLE1 NM_001499.2(GLE1):c.1882-2A>GSNV Pathogenic 619141 rs1336481358 9:131301893-131301893 9:128539614-128539614
5 GLE1 NM_001003722.1(GLE1):c.100-7_100-3deldeletion Pathogenic 619142
6 GLE1 NM_001003722.1(GLE1):c.2078C>T (p.Ser693Phe)SNV Pathogenic 619143 rs1564162129 9:131303430-131303430 9:128541151-128541151
7 GLE1 NM_001499.2(GLE1):c.1750C>T (p.Arg584Trp)SNV Pathogenic 619144 rs765269946 9:131298737-131298737 9:128536458-128536458
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.1641T>C (p.Tyr547=)SNV Uncertain significance 193820 rs77053118 9:131296225-131296225 9:128533946-128533946
11 GLE1 NM_001003722.1(GLE1):c.*390C>TSNV Uncertain significance 365140 rs886063491 9:131303839-131303839 9:128541560-128541560
12 GLE1 NM_001003722.1(GLE1):c.*933A>CSNV Uncertain significance 365146 rs537244282 9:131304382-131304382 9:128542103-128542103
13 GLE1 NM_001499.2(GLE1):c.-108C>ASNV Uncertain significance 365126 rs545478697 9:131266977-131266977 9:128504698-128504698
14 GLE1 NM_001499.2(GLE1):c.749C>T (p.Ala250Val)SNV Uncertain significance 365134 rs886063489 9:131285977-131285977 9:128523698-128523698
15 GLE1 NM_001003722.1(GLE1):c.2028+15G>ASNV Uncertain significance 365135 rs886063490 9:131302632-131302632 9:128540353-128540353
16 GLE1 NM_001003722.1(GLE1):c.*640C>TSNV Uncertain significance 365142 rs575049150 9:131304089-131304089 9:128541810-128541810
17 GLE1 NM_001499.2(GLE1):c.-81C>TSNV Uncertain significance 365128 rs56214514 9:131267004-131267004 9:128504725-128504725
18 GLE1 NM_001499.2(GLE1):c.54C>G (p.Asp18Glu)SNV Uncertain significance 365131 rs549769200 9:131267138-131267138 9:128504859-128504859
19 GLE1 NM_001003722.1(GLE1):c.*111T>CSNV Uncertain significance 365137 rs567740764 9:131303560-131303560 9:128541281-128541281
20 GLE1 NM_001499.2(GLE1):c.-84A>CSNV Uncertain significance 365127 rs886063488 9:131267001-131267001 9:128504722-128504722
21 GLE1 NM_001499.2(GLE1):c.321+13T>GSNV Uncertain significance 365132 rs752458769 9:131271389-131271389 9:128509110-128509110
22 GLE1 NM_001499.2(GLE1):c.679C>T (p.Arg227Cys)SNV Uncertain significance 284416 rs146025848 9:131285907-131285907 9:128523628-128523628
23 GLE1 NM_001499.2(GLE1):c.5C>G (p.Pro2Arg)SNV Uncertain significance 285426 rs150246404 9:131267089-131267089 9:128504810-128504810
24 GLE1 NM_001499.2(GLE1):c.1393T>A (p.Ser465Thr)SNV Uncertain significance 289027 rs141709685 9:131295872-131295872 9:128533593-128533593
25 GLE1 NM_001499.2(GLE1):c.-51G>ASNV Uncertain significance 365129 rs527886091 9:131267034-131267034 9:128504755-128504755
26 GLE1 NM_001499.2(GLE1):c.-45T>CSNV Uncertain significance 365130 rs372008961 9:131267040-131267040 9:128504761-128504761
27 GLE1 NM_001499.2(GLE1):c.433-15A>CSNV Uncertain significance 365133 rs752897261 9:131284932-131284932 9:128522653-128522653
28 GLE1 NM_001003722.1(GLE1):c.*540G>ASNV Uncertain significance 365141 rs886063492 9:131303989-131303989 9:128541710-128541710
29 GLE1 NM_001003722.1(GLE1):c.*708T>CSNV Uncertain significance 365143 rs886063493 9:131304157-131304157 9:128541878-128541878
30 GLE1 NM_001003722.1(GLE1):c.*782C>GSNV Uncertain significance 365144 rs886063494 9:131304231-131304231 9:128541952-128541952
31 GLE1 NM_001003722.1(GLE1):c.*907G>CSNV Likely benign 365145 rs55823126 9:131304356-131304356 9:128542077-128542077
32 GLE1 NM_001003722.1(GLE1):c.*1005T>CSNV Likely benign 365147 rs4466499 9:131304454-131304454 9:128542175-128542175
33 GLE1 NM_001003722.1(GLE1):c.*387C>GSNV Likely benign 365139 rs78624767 9:131303836-131303836 9:128541557-128541557
34 GLE1 NM_001003722.1(GLE1):c.*181C>ASNV Likely benign 365138 rs10513496 9:131303630-131303630 9:128541351-128541351
35 GLE1 NM_001499.2(GLE1):c.1000G>A (p.Glu334Lys)SNV Benign/Likely benign 256855 rs138310419 9:131287573-131287573 9:128525294-128525294
36 GLE1 NM_001499.2(GLE1):c.727A>G (p.Ile243Val)SNV Benign 198109 rs2275260 9:131285955-131285955 9:128523676-128523676
37 GLE1 NM_001003722.1(GLE1):c.*73G>ASNV Benign 365136 rs10760563 9:131303522-131303522 9:128541243-128541243

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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