ALKKUCS
MCID: ALK024
MIFTS: 43

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 56 12 73 6
Arthrogryposis 43 39 17 71
Alkkucs 56 12 73

Characteristics:

OMIM:

56
Inheritance:
autosomal recessive

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


HPO:

31
alkuraya-kucinskas syndrome:
Inheritance autosomal recessive inheritance
Onset and clinical course congenital onset


Classifications:



Summaries for Alkuraya-Kucinskas Syndrome

UniProtKB/Swiss-Prot : 73 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 Analgesics have been mentioned in the context of this disorder. Affiliated tissues include brain, bone and skeletal muscle, and related phenotypes are seizures and pericardial effusion

Disease Ontology : 12 A syndrome characterized by arthrogryposis, cerebral parenchymal underdevelopment, clubfoot, and global developmental delay with severe cases being incompatible with life that has material basis in homozygous or compound heterozygous mutation in KIAA1109 on chromosome 4q27.

OMIM : 56 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 512)
# Related Disease Score Top Affiliating Genes
1 arthrogryposis, distal, type 1a 12.9
2 distal arthrogryposis 12.8
3 arthrogryposis, distal, type 5 12.7
4 arthrogryposis multiplex congenita, neurogenic type 12.7
5 arthrogryposis, renal dysfunction, and cholestasis 1 12.7
6 arthrogryposis, distal, type 2b1 12.7
7 arthrogryposis, distal, type 3 12.7
8 arthrogryposis, distal, type 5d 12.7
9 arthrogryposis multiplex congenita, myogenic type 12.6
10 arthrogryposis, distal, type 6 12.6
11 arthrogryposis, distal, type 2a 12.6
12 arthrogryposis, distal, type 4 12.6
13 congenital arthrogryposis with anterior horn cell disease 12.6
14 arthrogryposis, distal, type 2b2 12.6
15 arthrogryposis, distal, type 1b 12.6
16 arthrogryposis, mental retardation, and seizures 12.6
17 arthrogryposis, renal dysfunction, and cholestasis 2 12.6
18 arthrogryposis, distal, type 2b3 12.5
19 muscular dystrophy, congenital, producing arthrogryposis 12.5
20 arthrogryposis, perthes disease, and upward gaze palsy 12.5
21 arthrogryposis multiplex congenita, neurogenic, with myelin defect 12.5
22 arthrogryposis, distal, with impaired proprioception and touch 12.5
23 arthrogryposis, distal, type 10 12.5
24 polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis 12.5
25 arthrogryposis, distal, type 7 12.4
26 neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies 12.4
27 arthrogryposis, cleft palate, craniosynostosis, and impaired intellectual development 12.4
28 pelvic hypoplasia with lower-limb arthrogryposis 12.3
29 arthrogryposis multiplex congenita, neurogenic, with agenesis of the corpus callosum 12.3
30 malignant hyperthermia arthrogryposis torticollis 12.3
31 arthrogryposis with hyperkeratosis 12.3
32 spinal muscular atrophy, x-linked 2 12.3
33 arthrogryposis, ectodermal dysplasia, cleft lip/palate, and developmental delay 12.3
34 arthrogryposis and ectodermal dysplasia 12.3
35 arthrogryposis, congenital, lower limb, x-linked 12.2
36 neuropathy, congenital, with arthrogryposis multiplex 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 illum syndrome 12.1
47 contractural arachnodactyly, congenital 12.1
48 arthrogryposis iugr thoracic dystrophy 12.0
49 arthrogryposis multiplex congenita cns calcification 12.0
50 arthrogryposis spinal muscular atrophy 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:

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

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Head:
macrocephaly

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

Neurologic Central Nervous System:
intellectual disability
hydrocephalus
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):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Adenosine Approved, Investigational 58-61-7 60961
2 Analgesics
3 Anti-Arrhythmia Agents
4 Neurotransmitter Agents
5 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:

40
Brain, Bone, Skeletal Muscle, Liver, Eye, Skin, Heart

Publications for Alkuraya-Kucinskas Syndrome

Articles related to Alkuraya-Kucinskas Syndrome:

(show top 50) (show all 1975)
# Title Authors PMID Year
1
KIAA1109 Variants Are Associated with a Severe Disorder of Brain Development and Arthrogryposis. 61 56 6
29290337 2018
2
Accelerating novel candidate gene discovery in neurogenetic disorders via whole-exome sequencing of prescreened multiplex consanguineous families. 56 6
25558065 2015
3
Tweek, an evolutionarily conserved protein, is required for synaptic vesicle recycling. 56
19640479 2009
4
Cerebral Palsy in Children With Congenital Zika Syndrome: A 2-Year Neurodevelopmental Follow-up. 61
31718421 2020
5
An uncommon case of arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome and review of the renal involvement: Questions. 61
31463585 2020
6
An uncommon case of arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome and review of the renal involvement: Answers. 61
31463586 2020
7
Patient-reported Outcomes in Arthrogryposis. 61
32040062 2020
8
Orthopaedic care of the child with arthrogryposis: a 2020 overview. 61
31743218 2020
9
The 5-Year Outcome of the Ponseti Method in Children With Idiopathic Clubfoot and Arthrogryposis. 61
32032217 2020
10
Body wall defects and amniotic band syndrome in pig (Sus scrofa domesticus). 61
31513296 2020
11
Biallelic loss of function variants in ATP1A2 cause hydrops fetalis, microcephaly, arthrogryposis and extensive cortical malformations. 61
30690204 2020
12
Recessive mutations in SCYL2 cause a novel syndromic form of arthrogryposis in humans. 61
31960134 2020
13
Identification of a novel pathogenic mutation of the MYH3 gene in a family with distal arthrogryposis type 2B. 61
31746383 2020
14
Tension band plate-guided growth of knee-flexion deformity in arthrogryposis multiplex congenita in which metaphyseal funnelization induced screw encroachment upon the neurovascular bundle. 61
31305362 2020
15
A new case of SMABF2 diagnosed in stillbirth expands the prenatal presentation and mutational spectrum of ASCC1. 61
31880396 2019
16
Orthopedic findings in arthrogryposis and congenital Zika syndrome: A case series. 61
31891236 2019
17
Novel in-frame FLNB deletion causes Larsen syndrome in a three-generation pedigree. 61
31836586 2019
18
Schaaf-Yang syndrome shows a Prader-Willi syndrome-like phenotype during infancy. 61
31791363 2019
19
Mutations in MAGEL2 and L1CAM Are Associated With Congenital Hypopituitarism and Arthrogryposis. 61
31504653 2019
20
[THE CONGENITAL TRIGGER THUMB - CLINICAL PRESENTATION AND TREATMENT]. 61
31823534 2019
21
Novel missense mutation in VPS33B is associated with isolated low gamma-glutamyltransferase cholestasis: Attenuated, incomplete phenotype of arthrogryposis, renal dysfunction, and cholestasis syndrome. 61
31479177 2019
22
Expanding the clinical and molecular spectrum of Lethal Congenital Contracture Syndrome 8 associated with biallelic variants of ADCY6. 61
31846058 2019
23
Arthrogryposis. 61
31787162 2019
24
Deleterious de novo variants of X-linked ZC4H2 in females cause a variable phenotype with neurogenic arthrogryposis multiplex congenita. 61
31206972 2019
25
Host and viral mechanisms of congenital Zika syndrome. 61
31451049 2019
26
X-linked infantile spinal muscular atrophy (SMAX2) caused by novel c.1681G>A substitution in the UBA1 gene, expanding the phenotype. 61
31932168 2019
27
A Novel VPS33B Variant Identified by Exome Sequencing in a Patient with Arthrogryposis-Renal Dysfunction-Cholestasis Syndrome. 61
31777725 2019
28
The genomic and clinical landscape of fetal akinesia. 61
31680123 2019
29
One-stage release by double surgical approach for neglected congenital vertical talus: results in a series of walking children in Tanzania. 61
31356505 2019
30
Diaphragmatic paralysis: Evaluation in infants with congenital Zika syndrome. 61
31595718 2019
31
Effects of Abnormal Muscle Forces on Prenatal Joint Morphogenesis in Mice. 61
31297860 2019
32
Subclinical in utero Zika virus infection is associated with interferon alpha sequelae and sex-specific molecular brain pathology in asymptomatic porcine offspring. 61
31725819 2019
33
Nerve transfer from the median to musculocutaneous nerve to induce active elbow flexion in selected cases of arthrogryposis multiplex congenita. 61
30891796 2019
34
Proximal Junctional Kyphosis After Posterior Spinal Fusion for Severe Kyphoscoliosis in a Patient With PIEZO2-deficient Arthrogryposis Syndrome. 61
31770315 2019
35
Novel SPEG variant cause centronuclear myopathy in China. 61
31625632 2019
36
Loss of SMPD4 Causes a Developmental Disorder Characterized by Microcephaly and Congenital Arthrogryposis. 61
31495489 2019
37
Recurrent TTN metatranscript-only c.39974-11T>G splice variant associated with autosomal recessive arthrogryposis multiplex congenita and myopathy. 61
31660661 2019
38
The Effects of Age on the Outcomes of Elbow Release in Arthrogryposis. 61
30660396 2019
39
Novel ASCC1 mutations causing prenatal-onset muscle weakness with arthrogryposis and congenital bone fractures. 61
30327447 2019
40
Biallelic TOR1A mutations cause severe arthrogryposis: A case requiring reverse phenotyping. 61
30244176 2019
41
The diagnostic workup in a patient with AMC: Overview of the clinical evaluation and paraclinical analyses with review of the literature. 61
31368648 2019
42
Classification of arthrogryposis. 61
31271512 2019
43
Central nervous system involvement in arthrogryposis multiplex congenita: Overview of causes, diagnosis, and care. 61
31410997 2019
44
Fetal cervical hyperextension in arthrogryposis. 61
31350810 2019
45
Disease coding systems for arthrogryposis multiplex congenita. 61
31232506 2019
46
Pain among children and adults living with arthrogryposis multiplex congenita: A scoping review. 61
31347265 2019
47
Muscle and joint function in children living with arthrogryposis multiplex congenita: A scoping review. 61
31350946 2019
48
Perspectives on gait and motion analysis in the management of youth with arthrogryposis multiplex congenita. 61
31359604 2019
49
Research platform for children with arthrogryposis multiplex congenita: Findings from the pilot registry. 61
31359631 2019
50
International multidisciplinary collaboration toward an annotated definition of arthrogryposis multiplex congenita. 61
31282072 2019

Variations for Alkuraya-Kucinskas Syndrome

ClinVar genetic disease variations for Alkuraya-Kucinskas Syndrome:

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 KIAA1109 NM_015312.3(KIAA1109):c.3986A>G (p.Tyr1329Cys)SNV Pathogenic 487547 rs770791100 4:123160823-123160823 4:122239668-122239668
2 KIAA1109 NM_015312.3(KIAA1109):c.5599G>A (p.Val1867Met)SNV Pathogenic 487548 rs1554025656 4:123170726-123170726 4:122249571-122249571
3 KIAA1109 NM_015312.3(KIAA1109):c.3611del (p.Asn1204fs)deletion Pathogenic 487549 rs775516790 4:123159280-123159280 4:122238125-122238125
4 KIAA1109 NM_015312.3(KIAA1109):c.2902C>T (p.Arg968Cys)SNV Pathogenic 487550 rs1051597475 4:123147970-123147970 4:122226815-122226815
5 KIAA1109 NM_015312.3(KIAA1109):c.10153G>C (p.Gly3385Arg)SNV Pathogenic 487551 rs1554059454 4:123230520-123230520 4:122309365-122309365
6 KIAA1109 NM_015312.3(KIAA1109):c.1557T>A (p.Tyr519Ter)SNV Pathogenic/Likely pathogenic 183349 rs730882245 4:123128323-123128323 4:122207168-122207168
7 KIAA1109 NM_015312.3(KIAA1109):c.1381-2A>GSNV Likely pathogenic 804447 4:123122162-123122162 4:122201007-122201007
8 KIAA1109 NM_015312.3(KIAA1109):c.439C>T (p.Arg147Cys)SNV Uncertain significance 523045 rs779054376 4:123107271-123107271 4:122186116-122186116
9 KIAA1109 NM_015312.3(KIAA1109):c.1183del (p.Ile395fs)deletion Uncertain significance 800986 4:123117919-123117919 4:122196764-122196764

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 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
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50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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