TOKAS
MCID: TNN015
MIFTS: 30

Tonne-Kalscheuer Syndrome (TOKAS)

Categories: Genetic diseases, Mental diseases, Neuronal diseases, Reproductive diseases

Aliases & Classifications for Tonne-Kalscheuer Syndrome

MalaCards integrated aliases for Tonne-Kalscheuer Syndrome:

Name: Tonne-Kalscheuer Syndrome 57 12 72
Mental Retardation, X-Linked 61 57 72 29 6
Tokas 57 12 72
Mrx61 57 12 72
Intellectual Developmental Disorder with or Without Hand and Foot Anomalies, Genital Anomalies, or Congenital Diaphragmatic Hernia 57 12
Mental Retardation, X-Linked 61; Mrx61 57
X-Linked Mental Retardation 61 12
Syndrome, Tonne-Kalscheuer 39

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Miscellaneous:
onset in utero or at birth
some patients die in the perinatal period due to congenital diaphragmatic hernia
carrier females may have mild distal skeletal abnormalities or premature ovarian insufficiency

Inheritance:
x-linked


HPO:

31
tonne-kalscheuer syndrome:
Inheritance x-linked recessive inheritance


Classifications:



Summaries for Tonne-Kalscheuer Syndrome

OMIM® : 57 Tonne-Kalscheuer syndrome (TOKAS) is an X-linked recessive multiple congenital anomaly disorder with 2 main presentations. Most patients exhibit global developmental delay apparent from early infancy, impaired intellectual development, speech delay, behavioral abnormalities, and abnormal gait. Affected individuals also have dysmorphic facial features that evolve with age, anomalies of the hands, feet, and nails, and urogenital abnormalities with hypogenitalism. A subset of more severely affected males develop congenital diaphragmatic hernia in utero, which may result in perinatal or premature death. Carrier females may have very mild skeletal or hormonal abnormalities (summary by Frints et al., 2019). Also see Fryns syndrome (229850), an autosomal recessive disorder with overlapping features. (300978) (Updated 05-Apr-2021)

MalaCards based summary : Tonne-Kalscheuer Syndrome, also known as mental retardation, x-linked 61, is related to fryns syndrome. An important gene associated with Tonne-Kalscheuer Syndrome is RLIM (Ring Finger Protein, LIM Domain Interacting). Affiliated tissues include heart, brain and lung, and related phenotypes are congenital diaphragmatic hernia and pulmonary hypoplasia

Disease Ontology : 12 A syndromic X-linked intellectual disability characterized by global developmental delay, impaired intellectual development, speech delay, and behavioral abnormalities in most patients and variable congenital anomalies in some patients that has material basis in mutation in RLIM on chromosome Xq13.2.

UniProtKB/Swiss-Prot : 72 Tonne-Kalscheuer syndrome: An X-linked disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non-syndromic X-linked mental retardation, while syndromic mental retardation presents with associated physical, neurological and/or psychiatric manifestations.

Related Diseases for Tonne-Kalscheuer Syndrome

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

# Related Disease Score Top Affiliating Genes
1 fryns syndrome 11.3

Symptoms & Phenotypes for Tonne-Kalscheuer Syndrome

Human phenotypes related to Tonne-Kalscheuer Syndrome:

31 (show all 43)
# Description HPO Frequency HPO Source Accession
1 congenital diaphragmatic hernia 31 very rare (1%) HP:0000776
2 pulmonary hypoplasia 31 very rare (1%) HP:0002089
3 abnormal heart morphology 31 very rare (1%) HP:0001627
4 intellectual disability 31 HP:0001249
5 spasticity 31 HP:0001257
6 hyperreflexia 31 HP:0001347
7 tremor 31 HP:0001337
8 dysphagia 31 HP:0002015
9 self-injurious behavior 31 HP:0100716
10 global developmental delay 31 HP:0001263
11 hypertelorism 31 HP:0000316
12 behavioral abnormality 31 HP:0000708
13 wide nasal bridge 31 HP:0000431
14 delayed speech and language development 31 HP:0000750
15 pes planus 31 HP:0001763
16 microcephaly 31 HP:0000252
17 short stature 31 HP:0004322
18 broad thumb 31 HP:0011304
19 cryptorchidism 31 HP:0000028
20 micrognathia 31 HP:0000347
21 anxiety 31 HP:0000739
22 narrow face 31 HP:0000275
23 downslanted palpebral fissures 31 HP:0000494
24 narrow mouth 31 HP:0000160
25 brachydactyly 31 HP:0001156
26 downturned corners of mouth 31 HP:0002714
27 micropenis 31 HP:0000054
28 fine hair 31 HP:0002213
29 malar flattening 31 HP:0000272
30 prominent nasal bridge 31 HP:0000426
31 hypospadias 31 HP:0000047
32 broad forehead 31 HP:0000337
33 hypotelorism 31 HP:0000601
34 decreased testicular size 31 HP:0008734
35 broad-based gait 31 HP:0002136
36 feeding difficulties 31 HP:0011968
37 prominent nose 31 HP:0000448
38 aggressive behavior 31 HP:0000718
39 generalized hypotonia 31 HP:0001290
40 small nail 31 HP:0001792
41 poor speech 31 HP:0002465
42 velopharyngeal insufficiency 31 HP:0000220
43 shyness 31 HP:0100962

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
spasticity
hyperreflexia
tremor
broad-based gait
poor speech
more
Head And Neck Eyes:
hypertelorism
hypotelorism
downslanting palpebral fissures
straight lateral eyebrows

Head And Neck Head:
microcephaly

Genitourinary External Genitalia Male:
cryptorchidism
hypospadias
small penis
small testes

Skeletal Hands:
brachydactyly
broad thumbs

Abdomen Gastrointestinal:
velopharyngeal insufficiency
swallowing difficulties

Growth Other:
growth retardation
lean build

Cardiovascular Heart:
congenital heart defects (in some patients)

Skin Nails Hair Nails:
nail hypoplasia
abnormal nails

Chest Diaphragm:
congenital diaphragmatic hernia (in some patients)

Neurologic Behavioral Psychiatric Manifestations:
self-injurious behavior
anxiety
aggressive behavior
shyness
autistic features
more
Skeletal Feet:
pes planus

Growth Height:
short stature

Head And Neck Face:
micrognathia
broad forehead
malar hypoplasia
long narrow face

Skin Nails Hair Hair:
fine hair
receding hairline

Muscle Soft Tissue:
hypotonia

Head And Neck Nose:
broad nasal bridge
high nasal bridge
large nose

Head And Neck Mouth:
small mouth
downturned corners of the mouth

Respiratory Lung:
lung hypoplasia (in some patients)

Endocrine Features:
female carriers may have premature ovarian insufficiency

Clinical features from OMIM®:

300978 (Updated 05-Apr-2021)

Drugs & Therapeutics for Tonne-Kalscheuer Syndrome

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Clinical Evaluations of the TOKA Customized Device for High Tibial Osteotomy in the Treatment of Knee Osteoarthritis: a Pilot Study. Recruiting NCT04574570
2 Personalised Against Standard High Tibial Osteotomy, a Prospective Multi-centre Randomised Controlled Trial Not yet recruiting NCT04666571

Search NIH Clinical Center for Tonne-Kalscheuer Syndrome

Genetic Tests for Tonne-Kalscheuer Syndrome

Genetic tests related to Tonne-Kalscheuer Syndrome:

# Genetic test Affiliating Genes
1 Mental Retardation, X-Linked 61 29 RLIM

Anatomical Context for Tonne-Kalscheuer Syndrome

MalaCards organs/tissues related to Tonne-Kalscheuer Syndrome:

40
Heart, Brain, Lung, Testes

Publications for Tonne-Kalscheuer Syndrome

Articles related to Tonne-Kalscheuer Syndrome:

# Title Authors PMID Year
1
Pathogenic variants in E3 ubiquitin ligase RLIM/RNF12 lead to a syndromic X-linked intellectual disability and behavior disorder. 6 57
29728705 2019
2
X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes. 6 57
25644381 2016
3
Syndromic X-linked intellectual disability segregating with a missense variant in RLIM. 57 6
25735484 2015
4
Re: Critical Analysis of Early Recurrence after Laparoscopic Radical Cystectomy in a Large Cohort by the ESUT: S. Albisinni, L. Fossion, M. Oderda, O. M. Aboumarzouk, F. Aoun, T. Tokas, V. Varca, R. Sanchez-Salas, X. Cathelineau, P. Chlosta, F. Gaboardi, U. Nagele, T. Piechaud, J. Rassweiler, P. Rimington, L. Salomon and R. van Velthoven J Urol 2016;195:1710-1717. 61
27393901 2016

Variations for Tonne-Kalscheuer Syndrome

ClinVar genetic disease variations for Tonne-Kalscheuer Syndrome:

6 (show all 11)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 RLIM NM_016120.4(RLIM):c.1159C>T (p.Arg387Cys) SNV Pathogenic 253088 rs1569309776 GRCh37: X:73811991-73811991
GRCh38: X:74592156-74592156
2 RLIM NM_016120.4(RLIM):c.1795C>T (p.Arg599Cys) SNV Pathogenic 253089 rs1569309459 GRCh37: X:73811355-73811355
GRCh38: X:74591520-74591520
3 RLIM NM_016120.4(RLIM):c.1760C>G (p.Pro587Arg) SNV Pathogenic 253087 rs1569309474 GRCh37: X:73811390-73811390
GRCh38: X:74591555-74591555
4 RLIM NM_016120.4(RLIM):c.1792G>A (p.Asp598Asn) SNV Pathogenic 585243 rs1569309460 GRCh37: X:73811358-73811358
GRCh38: X:74591523-74591523
5 RLIM NM_016120.4(RLIM):c.1093C>T (p.Arg365Cys) SNV Pathogenic 585244 rs1569309816 GRCh37: X:73812057-73812057
GRCh38: X:74592222-74592222
6 RLIM NM_016120.4(RLIM):c.1831C>T (p.Arg611Cys) SNV Pathogenic 585245 rs1569309449 GRCh37: X:73811319-73811319
GRCh38: X:74591484-74591484
7 RLIM NM_016120.4(RLIM):c.1067A>G (p.Tyr356Cys) SNV Pathogenic 156224 rs786205133 GRCh37: X:73812083-73812083
GRCh38: X:74592248-74592248
8 RLIM NM_016120.4(RLIM):c.1262A>G (p.Tyr421Cys) SNV Likely pathogenic 979167 GRCh37: X:73811888-73811888
GRCh38: X:74592053-74592053
9 RLIM NM_016120.4(RLIM):c.1729T>C (p.Tyr577His) SNV Likely pathogenic 598940 rs1569309484 GRCh37: X:73811421-73811421
GRCh38: X:74591586-74591586
10 RLIM NM_016120.4(RLIM):c.1364C>A (p.Ser455Tyr) SNV Uncertain significance 635529 rs1478259309 GRCh37: X:73811786-73811786
GRCh38: X:74591951-74591951
11 RLIM NM_016120.4(RLIM):c.736A>G (p.Ile246Val) SNV Uncertain significance 1030534 GRCh37: X:73812414-73812414
GRCh38: X:74592579-74592579

UniProtKB/Swiss-Prot genetic disease variations for Tonne-Kalscheuer Syndrome:

72
# Symbol AA change Variation ID SNP ID
1 RLIM p.Tyr356Cys VAR_077826 rs786205133
2 RLIM p.Arg387Cys VAR_077827
3 RLIM p.Pro587Arg VAR_077828
4 RLIM p.Arg599Cys VAR_077829

Expression for Tonne-Kalscheuer Syndrome

Search GEO for disease gene expression data for Tonne-Kalscheuer Syndrome.

Pathways for Tonne-Kalscheuer Syndrome

GO Terms for Tonne-Kalscheuer Syndrome

Sources for Tonne-Kalscheuer Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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