ALKKUCS
MCID: ALK024
MIFTS: 41

Alkuraya-Kucinskas Syndrome (ALKKUCS)

Categories: Genetic diseases, Neuronal diseases

Aliases & Classifications for Alkuraya-Kucinskas Syndrome

MalaCards integrated aliases for Alkuraya-Kucinskas Syndrome:

Name: Alkuraya-Kucinskas Syndrome 57 74 6
Arthrogryposis 44 40 17 72
Alkkucs 57 74

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
onset in utero
most affected individuals die in utero or soon after birth


HPO:

32
alkuraya-kucinskas syndrome:
Inheritance autosomal recessive inheritance
Onset and clinical course congenital onset


Classifications:



External Ids:

OMIM 57 617822
UMLS 72 C0003886

Summaries for Alkuraya-Kucinskas Syndrome

UniProtKB/Swiss-Prot : 74 Alkuraya-Kucinskas syndrome: An autosomal recessive syndrome characterized by brain atrophy and arthrogryposis. Patients present with cerebral parenchymal underdevelopment, lissencephaly, severe to mild ventriculomegaly, and cerebellar hypoplasia with brainstem dysgenesis. Most affected individuals die in utero or soon after birth. The few patients who survive have variable intellectual disability and may have seizures. Facial dysmorphism, cardiac and ophthalmologic anomalies, such as microphthalmia and cataract, are additional features.

MalaCards based summary : Alkuraya-Kucinskas Syndrome, also known as arthrogryposis, is related to arthrogryposis, distal, type 1a and distal arthrogryposis, and has symptoms including muscle weakness, arthralgia and myalgia. An important gene associated with Alkuraya-Kucinskas Syndrome is KIAA1109 (KIAA1109). The drugs Adenosine and Neurotransmitter Agents have been mentioned in the context of this disorder. Affiliated tissues include brain, skeletal muscle and bone, and related phenotypes are seizures and pericardial effusion

OMIM : 57 ALKKUCS is an autosomal recessive severe neurodevelopmental disorder characterized by arthrogryposis, brain abnormalities associated with cerebral parenchymal underdevelopment, and global developmental delay. Most affected individuals die in utero or soon after birth. Additional abnormalities may include hypotonia, dysmorphic facial features, and involvement of other organ systems, such as cardiac or renal. The few patients who survive have variable intellectual disability and may have seizures (summary by Gueneau et al., 2018). (617822)

Related Diseases for Alkuraya-Kucinskas Syndrome

Diseases related to Alkuraya-Kucinskas Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 517)
# Related Disease Score Top Affiliating Genes
1 arthrogryposis, distal, type 1a 12.9
2 distal arthrogryposis 12.8
3 arthrogryposis multiplex congenita, neurogenic type 12.7
4 arthrogryposis, distal, type 5 12.7
5 arthrogryposis, renal dysfunction, and cholestasis 1 12.7
6 arthrogryposis, distal, type 2b1 12.7
7 arthrogryposis, distal, type 3 12.6
8 arthrogryposis, distal, type 5d 12.6
9 congenital arthrogryposis with anterior horn cell disease 12.6
10 arthrogryposis, distal, type 2a 12.6
11 arthrogryposis, mental retardation, and seizures 12.6
12 arthrogryposis, distal, type 2b2 12.5
13 arthrogryposis, distal, type 4 12.5
14 arthrogryposis, renal dysfunction, and cholestasis 2 12.5
15 arthrogryposis, distal, type 2b3 12.5
16 muscular dystrophy, congenital, producing arthrogryposis 12.5
17 arthrogryposis, perthes disease, and upward gaze palsy 12.5
18 arthrogryposis, distal, type 1b 12.5
19 arthrogryposis, distal, with impaired proprioception and touch 12.5
20 arthrogryposis, distal, type 6 12.5
21 polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis 12.4
22 arthrogryposis multiplex congenita, neurogenic, with myelin defect 12.4
23 arthrogryposis, distal, type 7 12.4
24 arthrogryposis multiplex congenita, myogenic type 12.4
25 arthrogryposis, cleft palate, craniosynostosis, and impaired intellectual development 12.4
26 malignant hyperthermia arthrogryposis torticollis 12.3
27 arthrogryposis-like hand anomaly and sensorineural deafness 12.3
28 pelvic dysplasia arthrogryposis of lower limbs 12.3
29 spinal muscular atrophy, x-linked 2 12.3
30 arthrogryposis, ectodermal dysplasia, cleft lip/palate, and developmental delay 12.3
31 arthrogryposis and ectodermal dysplasia 12.3
32 arthrogryposis, congenital, lower limb, x-linked 12.2
33 arthrogryposis multiplex congenita whistling face 12.2
34 autosomal recessive myogenic arthrogryposis multiplex congenita 12.2
35 neuropathy, congenital, with arthrogryposis multiplex 12.2
36 arthrogryposis, distal, type 10 12.2
37 fetal akinesia deformation sequence 1 12.2
38 arthrogryposis multiplex with deafness, inguinal hernias, and early death 12.2
39 arthrogryposis, distal, with mental retardation and characteristic facies 12.1
40 spondylohypoplasia, arthrogryposis and popliteal pterygium 12.1
41 arthrogryposis, distal, type 2e 12.1
42 arthrogryposis, distal, with hypopituitarism, mental retardation, and facial anomalies 12.1
43 bruck syndrome 1 12.1
44 arthrogryposis epileptic seizures migrational brain disorder 12.1
45 minicore myopathy, antenatal onset, with arthrogryposis 12.1
46 contractural arachnodactyly, congenital 12.1
47 arthrogryposis with hyperkeratosis 12.0
48 pelvic hypoplasia with lower-limb arthrogryposis 12.0
49 illum syndrome 12.0
50 arthrogryposis iugr thoracic dystrophy 12.0

Graphical network of the top 20 diseases related to Alkuraya-Kucinskas Syndrome:



Diseases related to Alkuraya-Kucinskas Syndrome

Symptoms & Phenotypes for Alkuraya-Kucinskas Syndrome

Human phenotypes related to Alkuraya-Kucinskas Syndrome:

32 (show all 45)
# Description HPO Frequency HPO Source Accession
1 seizures 32 very rare (1%) HP:0001250
2 pericardial effusion 32 very rare (1%) HP:0001698
3 macrocephaly 32 HP:0000256
4 hypertelorism 32 HP:0000316
5 low-set ears 32 HP:0000369
6 clinodactyly 32 HP:0030084
7 high palate 32 HP:0000218
8 hydrocephalus 32 HP:0000238
9 intellectual disability 32 HP:0001249
10 cataract 32 HP:0000518
11 behavioral abnormality 32 HP:0000708
12 global developmental delay 32 HP:0001263
13 depressed nasal bridge 32 HP:0005280
14 short nose 32 HP:0003196
15 anteverted nares 32 HP:0000463
16 generalized hypotonia 32 HP:0001290
17 edema 32 HP:0000969
18 strabismus 32 HP:0000486
19 absent speech 32 HP:0001344
20 webbed neck 32 HP:0000465
21 cystic hygroma 32 HP:0000476
22 ventriculomegaly 32 HP:0002119
23 arthrogryposis multiplex congenita 32 HP:0002804
24 talipes equinovarus 32 HP:0001762
25 cerebellar hypoplasia 32 HP:0001321
26 micropenis 32 HP:0000054
27 upslanted palpebral fissure 32 HP:0000582
28 adducted thumb 32 HP:0001181
29 hypotelorism 32 HP:0000601
30 plagiocephaly 32 HP:0001357
31 aplasia/hypoplasia of the corpus callosum 32 HP:0007370
32 lissencephaly 32 HP:0001339
33 oculomotor apraxia 32 HP:0000657
34 scrotal hypoplasia 32 HP:0000046
35 cerebellar dysplasia 32 HP:0007033
36 camptodactyly 32 HP:0012385
37 overlapping fingers 32 HP:0010557
38 posteriorly rotated ears 32 HP:0000358
39 hand clenching 32 HP:0001188
40 hypermetropia 32 HP:0000540
41 cutaneous syndactyly 32 HP:0012725
42 overlapping toe 32 HP:0001845
43 hypoplasia of the brainstem 32 HP:0002365
44 gray matter heterotopia 32 HP:0002282
45 kinked brainstem 32 HP:0012793

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Head:
macrocephaly

Head And Neck Ears:
low-set ears
posteriorly rotated ears

Neurologic Central Nervous System:
hydrocephalus
intellectual disability
cerebellar hypoplasia
lissencephaly
cerebellar dysplasia
more
Muscle Soft Tissue:
edema
hypotonia

Skeletal Skull:
plagiocephaly

Head And Neck Mouth:
high-arched palate

Genitourinary External Genitalia Male:
hypoplastic scrotum
small penis

Head And Neck Face:
retrognathism

Respiratory:
breathing difficulties, neonatal

Respiratory Lung:
pleural effusions (in some patients)

Head And Neck Eyes:
hypertelorism
strabismus
hypotelorism
oculomotor apraxia
hypermetropia
more
Skeletal Hands:
clinodactyly
camptodactyly
overlapping fingers
adducted thumbs
clenched hands

Head And Neck Nose:
short nose
anteverted nares
flattened nasal bridge

Head And Neck Neck:
webbed neck
cystic hygroma

Skeletal Feet:
cutaneous syndactyly
overlapping toes
foot deformities
club feet

Neurologic Behavioral Psychiatric Manifestations:
behavioral problems

Skeletal:
arthrogryposis

Cardiovascular Heart:
cardiac defects (in some patients)
pericardial effusions (in some patients)

Genitourinary Kidneys:
renal defects (in some patients)

Skeletal Limbs:
flexion deformities

Clinical features from OMIM:

617822

UMLS symptoms related to Alkuraya-Kucinskas Syndrome:


muscle weakness, arthralgia, myalgia, muscle cramp, metatarsalgia, muscle rigidity, muscle spasticity

Drugs & Therapeutics for Alkuraya-Kucinskas Syndrome

Drugs for Alkuraya-Kucinskas Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 7)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Adenosine Approved, Investigational 58-61-7 60961
2 Neurotransmitter Agents
3 Analgesics
4 Peripheral Nervous System Agents
5 Purinergic P1 Receptor Agonists
6 Anti-Arrhythmia Agents
7 Vasodilator Agents

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Effects of Power Mobility on the Development and Function of Young Children With Severe Motor Impairments Completed NCT01028833 Phase 2
2 WREX Outcome Study Unknown status NCT02218593
3 An Innovative Device for Intervention in Infants With Nervous System Injury Completed NCT01959581
4 Study of Therapeutic Outcomes and Practices in Freeman-Sheldon Syndrome Recruiting NCT01144741
5 Freeman-Sheldon Syndrome Evaluation and Diagnosis in Clinical Settings (FSS-EDICT) I: a Case-Control, Cross-Sectional Study of Baseline and Stress Physiology Parameters Not yet recruiting NCT01306994
6 Freeman-Sheldon Syndrome Quality of Life Study (FSS-QLS): Cross-sectional Study of Concomitant Disorder-Specific Contributors to Quality of Life and Clinical Outcome Terminated NCT01307475

Search NIH Clinical Center for Alkuraya-Kucinskas Syndrome

Cochrane evidence based reviews: arthrogryposis

Genetic Tests for Alkuraya-Kucinskas Syndrome

Anatomical Context for Alkuraya-Kucinskas Syndrome

MalaCards organs/tissues related to Alkuraya-Kucinskas Syndrome:

41
Brain, Skeletal Muscle, Bone, Eye, Skin, Liver, Spinal Cord

Publications for Alkuraya-Kucinskas Syndrome

Articles related to Alkuraya-Kucinskas Syndrome:

(show top 50) (show all 1940)
# Title Authors PMID Year
1
KIAA1109 Variants Are Associated with a Severe Disorder of Brain Development and Arthrogryposis. 38 8 71
29290337 2018
2
Accelerating novel candidate gene discovery in neurogenetic disorders via whole-exome sequencing of prescreened multiplex consanguineous families. 8 71
25558065 2015
3
Tweek, an evolutionarily conserved protein, is required for synaptic vesicle recycling. 8
19640479 2009
4
Novel ASCC1 mutations causing prenatal-onset muscle weakness with arthrogryposis and congenital bone fractures. 38
30327447 2019
5
Heterozygous variants in MYBPC1 are associated with an expanded neuromuscular phenotype beyond arthrogryposis. 38
31264822 2019
6
Diagnosis of fetal non-chromosomal abnormalities on routine ultrasound examination at 11-13 weeks' gestation. 38
31408229 2019
7
Fetal arthrogryposis multiplex congenita/fetal akinesia deformation sequence (FADS)-Aetiology, diagnosis, and management. 38
31218730 2019
8
Central nervous system involvement in arthrogryposis multiplex congenita: Overview of causes, diagnosis, and care. 38
31410997 2019
9
The diagnostic workup in a patient with AMC: Overview of the clinical evaluation and paraclinical analyses with review of the literature. 38
31368648 2019
10
Predicting Ambulatory Function Based on Infantile Lower Extremity Posture Types in Amyoplasia Arthrogryposis. 38
30672764 2019
11
A Novel VPS33B Mutation Causing a Mild Phenotype of Arthrogryposis, Renal dysfunction, and Cholestasis Syndrome. 38
31343487 2019
12
Rehabilitation across the lifespan for individuals with arthrogryposis. 38
31397084 2019
13
Gene ontology analysis of arthrogryposis (multiple congenital contractures). 38
31369690 2019
14
A standardized autopsy protocol for arthrogryposis (multiple congenital contractures). 38
31373772 2019
15
Classification of arthrogryposis. 38
31271512 2019
16
Fetal cervical hyperextension in arthrogryposis. 38
31350810 2019
17
One-stage release by double surgical approach for neglected congenital vertical talus: results in a series of walking children in Tanzania. 38
31356505 2019
18
Characterization of Hand Anomalies Associated With Möbius Syndrome. 38
31031024 2019
19
SLC18A3 variants lead to fetal akinesia deformation sequence early in pregnancy. 38
31059209 2019
20
Treatment and outcomes of arthrogryposis in the upper extremity. 38
31268234 2019
21
Fetal arthrogryposis: Challenges and perspectives for prenatal detection and management. 38
31318155 2019
22
The relationship between joint surgery and quality of life in adults with arthrogryposis: An international study. 38
31260181 2019
23
Muscle and joint function in children living with arthrogryposis multiplex congenita: A scoping review. 38
31350946 2019
24
The Genomics of Arthrogryposis, a Complex Trait: Candidate Genes and Further Evidence for Oligogenic Inheritance. 38
31230720 2019
25
Pain among children and adults living with arthrogryposis multiplex congenita: A scoping review. 38
31347265 2019
26
International multidisciplinary collaboration toward an annotated definition of arthrogryposis multiplex congenita. 38
31282072 2019
27
Perspectives on gait and motion analysis in the management of youth with arthrogryposis multiplex congenita. 38
31359604 2019
28
Research platform for children with arthrogryposis multiplex congenita: Findings from the pilot registry. 38
31359631 2019
29
Quality of life, satisfaction with life, and functional mobility of young adults with arthrogryposis after leaving pediatric care. 38
31260186 2019
30
Tension band plate-guided growth of knee-flexion deformity in arthrogryposis multiplex congenita in which metaphyseal funnelization induced screw encroachment upon the neurovascular bundle. 38
31305362 2019
31
Effects of Abnormal Muscle Forces on Prenatal Joint Morphogenesis in Mice. 38
31297860 2019
32
Descriptive study of suspected congenital Zika syndrome cases during the 2015-2016 epidemic in Brazil. 38
31340371 2019
33
Distal arthrogryposis type 5 and PIEZO2 novel variant in a Canadian family. 38
30938034 2019
34
Nonimmune hydrops fetalis: identifying the underlying genetic etiology. 38
30410095 2019
35
Disease coding systems for arthrogryposis multiplex congenita. 38
31232506 2019
36
Elbow Flexion Assist Orthosis for Arthrogryposis. 38
31374678 2019
37
CHRNG-related nonlethal multiple pterygium syndrome: Muscle imaging pattern and clinical, histopathological, and molecular genetic findings. 38
30868735 2019
38
Challenging clubfeet: the arthrogrypotic clubfoot and the complex clubfoot. 38
31312267 2019
39
New Insights of a Neuronal Peptidase DINE/ECEL1: Nerve Development, Nerve Regeneration and Neurogenic Pathogenesis. 38
30357652 2019
40
Deleterious de novo variants of X-linked ZC4H2 in females cause a variable phenotype with neurogenic arthrogryposis multiplex congenita. 38
31206972 2019
41
Play with objects in children with arthrogryposis: Effects of intervention with the Playskin Lift™ exoskeletal garment. 38
31232529 2019
42
PIEZO2 deficiency is a recognizable arthrogryposis syndrome: A new case and literature review. 38
30941898 2019
43
Neu-Laxova syndrome presenting prenatally with increased nuchal translucency and cystic hygroma: The utility of exome sequencing in deciphering the diagnosis. 38
30838783 2019
44
SYNE1-ataxia: Novel genotypic and phenotypic findings. 38
30573412 2019
45
Autosomal recessive spinocerebellar ataxia SCAR8/ARCA1: First families detected in Spain. 38
31103315 2019
46
A novel mutation in VPS33B gene causing a milder ARC syndrome phenotype with prolonged survival. 38
31240160 2019
47
CORVET, CHEVI and HOPS - multisubunit tethers of the endo-lysosomal system in health and disease. 38
31092635 2019
48
Mutations in PIEZO2 contribute to Gordon syndrome, Marden-Walker syndrome and distal arthrogryposis: A bioinformatics analysis of mechanisms. 38
30988732 2019
49
Arthrogryposis in a Case of Chiari Malformation II: First Case Report in a Mediterranean Population. 38
31105263 2019
50
Development of an online registry for adults with arthrogryposis multiplex congenita: A protocol paper. 38
31099966 2019

Variations for Alkuraya-Kucinskas Syndrome

ClinVar genetic disease variations for Alkuraya-Kucinskas Syndrome:

6
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 KIAA1109 NM_015312.3(KIAA1109): c.3986A> G (p.Tyr1329Cys) single nucleotide variant Pathogenic rs770791100 4:123160823-123160823 4:122239668-122239668
2 KIAA1109 NM_015312.3(KIAA1109): c.5599G> A (p.Val1867Met) single nucleotide variant Pathogenic rs1554025656 4:123170726-123170726 4:122249571-122249571
3 KIAA1109 NM_015312.3(KIAA1109): c.3611del (p.Asn1204fs) deletion Pathogenic rs775516790 4:123159283-123159283 4:122238128-122238128
4 KIAA1109 NM_015312.3(KIAA1109): c.2902C> T (p.Arg968Cys) single nucleotide variant Pathogenic rs1051597475 4:123147970-123147970 4:122226815-122226815
5 KIAA1109 NM_015312.3(KIAA1109): c.10153G> C (p.Gly3385Arg) single nucleotide variant Pathogenic rs1554059454 4:123230520-123230520 4:122309365-122309365
6 KIAA1109 NM_015312.3(KIAA1109): c.1557T> A (p.Tyr519Ter) single nucleotide variant Pathogenic/Likely pathogenic rs730882245 4:123128323-123128323 4:122207168-122207168
7 KIAA1109 NM_015312.3(KIAA1109): c.439C> T (p.Arg147Cys) single nucleotide variant Uncertain significance rs779054376 4:123107271-123107271 4:122186116-122186116

Expression for Alkuraya-Kucinskas Syndrome

Search GEO for disease gene expression data for Alkuraya-Kucinskas Syndrome.

Pathways for Alkuraya-Kucinskas Syndrome

GO Terms for Alkuraya-Kucinskas Syndrome

Sources for Alkuraya-Kucinskas Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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