RTTCV
MCID: RTT008
MIFTS: 33

Rett Syndrome, Congenital Variant (RTTCV)

Categories: Genetic diseases, Mental diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Rett Syndrome, Congenital Variant

MalaCards integrated aliases for Rett Syndrome, Congenital Variant:

Name: Rett Syndrome, Congenital Variant 57 29 13 6 39
Rett Syndrome Congenital Variant 72
Rttcv 72

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal dominant

Miscellaneous:
all reported cases have occurred de novo
onset in the first months of life
normal birth
most patients do not learn to sit or walk
seizure onset after 3 months


HPO:

31
rett syndrome, congenital variant:
Inheritance autosomal dominant inheritance sporadic


Classifications:



Summaries for Rett Syndrome, Congenital Variant

UniProtKB/Swiss-Prot : 72 Rett syndrome congenital variant: A severe neurodevelopmental disorder with features of classic Rett syndrome but earlier onset in the first months of life. Clinical features include progressive microcephaly, hypotonia, irresponsiveness and irritability in the neonatal period, mental retardation, psychomotor regression and stereotypical movements.

MalaCards based summary : Rett Syndrome, Congenital Variant, also known as rett syndrome congenital variant, is related to rett syndrome, and has symptoms including seizures, constipation and athetosis. An important gene associated with Rett Syndrome, Congenital Variant is FOXG1 (Forkhead Box G1). Affiliated tissues include eye and tongue, and related phenotypes are spasticity and global developmental delay

OMIM® : 57 The congenital variant of Rett syndrome is a severe neurodevelopmental disorder with features of classic Rett syndrome (RTT; 312750), but earlier onset in the first months of life. Classic Rett syndrome shows later onset and is caused by mutation in the MECP2 gene (300005). (613454) (Updated 05-Apr-2021)

Related Diseases for Rett Syndrome, Congenital Variant

Diseases in the Rett Syndrome family:

Rett Syndrome, Congenital Variant

Diseases related to Rett Syndrome, Congenital Variant via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 rett syndrome 9.1 WDFY1 FOXG1 ARSJ

Symptoms & Phenotypes for Rett Syndrome, Congenital Variant

Human phenotypes related to Rett Syndrome, Congenital Variant:

31 (show all 43)
# Description HPO Frequency HPO Source Accession
1 spasticity 31 very rare (1%) HP:0001257
2 global developmental delay 31 very rare (1%) HP:0001263
3 gastroesophageal reflux 31 very rare (1%) HP:0002020
4 stereotypy 31 very rare (1%) HP:0000733
5 intellectual disability, severe 31 very rare (1%) HP:0010864
6 absent speech 31 very rare (1%) HP:0001344
7 irritability 31 very rare (1%) HP:0000737
8 pachygyria 31 very rare (1%) HP:0001302
9 hypoplasia of the corpus callosum 31 very rare (1%) HP:0002079
10 feeding difficulties 31 very rare (1%) HP:0011968
11 generalized hypotonia 31 very rare (1%) HP:0001290
12 aspiration 31 very rare (1%) HP:0002835
13 bruxism 31 very rare (1%) HP:0003763
14 impaired social interactions 31 very rare (1%) HP:0000735
15 progressive microcephaly 31 very rare (1%) HP:0000253
16 simplified gyral pattern 31 very rare (1%) HP:0009879
17 inappropriate crying 31 very rare (1%) HP:0030215
18 delayed ability to sit 31 very rare (1%) HP:0025336
19 delayed ability to walk 31 very rare (1%) HP:0031936
20 seizure 31 very rare (1%) HP:0001250
21 eeg abnormality 31 HP:0002353
22 scoliosis 31 HP:0002650
23 constipation 31 HP:0002019
24 kyphosis 31 HP:0002808
25 chorea 31 HP:0002072
26 developmental regression 31 HP:0002376
27 depressed nasal bridge 31 HP:0005280
28 pes planus 31 HP:0001763
29 dyskinesia 31 HP:0100660
30 neonatal hypotonia 31 HP:0001319
31 motor delay 31 HP:0001270
32 talipes equinovarus 31 HP:0001762
33 thin upper lip vermilion 31 HP:0000219
34 protruding ear 31 HP:0000411
35 bulbous nose 31 HP:0000414
36 dystonia 31 HP:0001332
37 midface retrusion 31 HP:0011800
38 poor eye contact 31 HP:0000817
39 athetosis 31 HP:0002305
40 drooling 31 HP:0002307
41 apraxia 31 HP:0002186
42 delayed myelination 31 HP:0012448
43 tongue thrusting 31 HP:0100703

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
seizures
spasticity
chorea
dyskinesia
neonatal hypotonia
more
Abdomen Gastrointestinal:
constipation
gastroesophageal reflux

Head And Neck Eyes:
poor eye contact

Respiratory:
abnormal breathing patterns

Growth Other:
slow postnatal growth

Skeletal Spine:
scoliosis
kyphosis

Skeletal Feet:
pes planus
equinovarus

Head And Neck Mouth:
bruxism
tongue thrusting
sialorrhea

Head And Neck Head:
microcephaly, postnatal, progressive

Skeletal Limbs:
genu valgu

Clinical features from OMIM®:

613454 (Updated 05-Apr-2021)

UMLS symptoms related to Rett Syndrome, Congenital Variant:


seizures; constipation; athetosis; muscle spasticity

Drugs & Therapeutics for Rett Syndrome, Congenital Variant

Search Clinical Trials , NIH Clinical Center for Rett Syndrome, Congenital Variant

Genetic Tests for Rett Syndrome, Congenital Variant

Genetic tests related to Rett Syndrome, Congenital Variant:

# Genetic test Affiliating Genes
1 Rett Syndrome, Congenital Variant 29 FOXG1

Anatomical Context for Rett Syndrome, Congenital Variant

MalaCards organs/tissues related to Rett Syndrome, Congenital Variant:

40
Eye, Tongue

Publications for Rett Syndrome, Congenital Variant

Articles related to Rett Syndrome, Congenital Variant:

(show all 34)
# Title Authors PMID Year
1
FOXG1 syndrome: genotype-phenotype association in 83 patients with FOXG1 variants. 57 6
28661489 2018
2
The core FOXG1 syndrome phenotype consists of postnatal microcephaly, severe mental retardation, absent language, dyskinesia, and corpus callosum hypogenesis. 6 57
21441262 2011
3
Novel FOXG1 mutations associated with the congenital variant of Rett syndrome. 57 6
19578037 2010
4
Phenotypic variability in Rett syndrome associated with FOXG1 mutations in females. 6 57
19564653 2010
5
Atypical Rett syndrome with selective FOXG1 deletion detected by comparative genomic hybridization: case report and review of literature. 6 57
19623215 2009
6
FOXG1 is responsible for the congenital variant of Rett syndrome. 6 57
18571142 2008
7
Diagnostic exome sequencing in 100 consecutive patients with both epilepsy and intellectual disability. 6
30525188 2019
8
Delineating FOXG1 syndrome: From congenital microcephaly to hyperkinetic encephalopathy. 6
30533527 2018
9
Diagnostic yield of targeted massively parallel sequencing in children with epileptic encephalopathy. 6
29852413 2018
10
Regulatory variants of FOXG1 in the context of its topological domain organisation. 6
29289958 2018
11
Novel FOXG1 mutations in Chinese patients with Rett syndrome or Rett-like mental retardation. 6
28851325 2017
12
A prospective evaluation of whole-exome sequencing as a first-tier molecular test in infants with suspected monogenic disorders. 6
26938784 2016
13
Delineation of the movement disorders associated with FOXG1 mutations. 6
27029630 2016
14
The hyperkinetic movement disorder of FOXG1-related epileptic-dyskinetic encephalopathy. 6
26344814 2016
15
Mutations in epilepsy and intellectual disability genes in patients with features of Rett syndrome. 6
25914188 2015
16
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. 6
25741868 2015
17
Gene Mutation Analysis in 253 Chinese Children with Unexplained Epilepsy and Intellectual/Developmental Disabilities. 6
26544041 2015
18
The usefulness of whole-exome sequencing in routine clinical practice. 6
24901346 2014
19
De novo mutations in moderate or severe intellectual disability. 6
25356899 2014
20
Epilepsy and outcome in FOXG1-related disorders. 6
24836831 2014
21
Somatic mosaicism for a FOXG1 mutation: diagnostic implication. 57
24766421 2014
22
Novel mutation in forkhead box G1 (FOXG1) gene in an Indian patient with Rett syndrome. 6
24412290 2014
23
14q12 microdeletions excluding FOXG1 give rise to a congenital variant Rett syndrome-like phenotype. 6
22968132 2013
24
14q12 and severe Rett-like phenotypes: new clinical insights and physical mapping of FOXG1-regulatory elements. 6
22739344 2012
25
FOXG1 mutations in Japanese patients with the congenital variant of Rett syndrome. 6
22129046 2012
26
Expanding the phenotype associated with FOXG1 mutations and in vivo FoxG1 chromatin-binding dynamics. 6
22091895 2012
27
West syndrome associated with mosaic duplication of FOXG1 in a patient with maternal uniparental disomy of chromosome 14. 57
21910242 2011
28
Analysis of FOXG1 Is Highly Recommended in Male and Female Patients with Rett Syndrome. 6
22190898 2011
29
[FOXG1, a new gene responsible for the congenital form of Rett syndrome]. 6
21488007 2011
30
Planning and core analyses for periodic aggregate safety data reviews. 6
21270142 2011
31
A FOXG1 mutation in a boy with congenital variant of Rett syndrome. 6
20734096 2011
32
A missense mutation within the fork-head domain of the forkhead box G1 Gene (FOXG1) affects its nuclear localization. 6
21280142 2011
33
Duplications of FOXG1 in 14q12 are associated with developmental epilepsy, mental retardation, and severe speech impairment. 57
20736978 2011
34
Revisiting the phenotype associated with FOXG1 mutations: two novel cases of congenital Rett variant. 6
19806373 2010

Variations for Rett Syndrome, Congenital Variant

ClinVar genetic disease variations for Rett Syndrome, Congenital Variant:

6 (show top 50) (show all 197)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 FOXG1 NM_005249.5(FOXG1):c.765G>A (p.Trp255Ter) SNV Pathogenic 13867 rs121913678 GRCh37: 14:29237250-29237250
GRCh38: 14:28768044-28768044
2 FOXG1 FOXG1, 1-BP DEL, 969C Deletion Pathogenic 13868 GRCh37:
GRCh38:
3 FOXG1 NM_005249.5(FOXG1):c.643T>C (p.Phe215Leu) SNV Pathogenic 13870 rs267606828 GRCh37: 14:29237128-29237128
GRCh38: 14:28767922-28767922
4 FOXG1 NM_005249.5(FOXG1):c.924G>A (p.Trp308Ter) SNV Pathogenic 13871 rs267606827 GRCh37: 14:29237409-29237409
GRCh38: 14:28768203-28768203
5 FOXG1 NM_005249.5(FOXG1):c.1200C>G (p.Tyr400Ter) SNV Pathogenic 13872 rs138747073 GRCh37: 14:29237685-29237685
GRCh38: 14:28768479-28768479
6 FOXG1 FOXG1, 1-BP DUP, 460G Duplication Pathogenic 29815 GRCh37:
GRCh38:
7 FOXG1 NM_005249.5(FOXG1):c.135_136dup (p.Gln46fs) Duplication Pathogenic 158587 rs587783629 GRCh37: 14:29236616-29236617
GRCh38: 14:28767410-28767411
8 FOXG1 NM_005249.5(FOXG1):c.170_179del (p.His57fs) Deletion Pathogenic 158589 rs587783631 GRCh37: 14:29236653-29236662
GRCh38: 14:28767447-28767456
9 FOXG1 NM_005249.5(FOXG1):c.263_278del (p.Arg88fs) Deletion Pathogenic 158593 rs587783635 GRCh37: 14:29236745-29236760
GRCh38: 14:28767539-28767554
10 FOXG1 NM_005249.5(FOXG1):c.757A>G (p.Asn253Asp) SNV Pathogenic 158599 rs587783641 GRCh37: 14:29237242-29237242
GRCh38: 14:28768036-28768036
11 FOXG1 NM_005249.5(FOXG1):c.762C>G (p.Tyr254Ter) SNV Pathogenic 158600 rs587783642 GRCh37: 14:29237247-29237247
GRCh38: 14:28768041-28768041
12 FOXG1 NM_005249.5(FOXG1):c.765G>T (p.Trp255Cys) SNV Pathogenic 158601 rs121913678 GRCh37: 14:29237250-29237250
GRCh38: 14:28768044-28768044
13 FOXG1 NM_005249.5(FOXG1):c.505_506delinsT (p.Gly169fs) Indel Pathogenic 189614 rs786205003 GRCh37: 14:29236990-29236991
GRCh38: 14:28767784-28767785
14 FOXG1 NM_005249.5(FOXG1):c.552dup (p.Ser185fs) Duplication Pathogenic 189615 rs786205004 GRCh37: 14:29237036-29237037
GRCh38: 14:28767830-28767831
15 FOXG1 NM_005249.5(FOXG1):c.577G>A (p.Ala193Thr) SNV Pathogenic 189616 rs786205005 GRCh37: 14:29237062-29237062
GRCh38: 14:28767856-28767856
16 FOXG1 NM_005249.5(FOXG1):c.689G>A (p.Arg230His) SNV Pathogenic 189618 rs786205007 GRCh37: 14:29237174-29237174
GRCh38: 14:28767968-28767968
17 FOXG1 NM_005249.5(FOXG1):c.700T>C (p.Ser234Pro) SNV Pathogenic 189619 rs786205008 GRCh37: 14:29237185-29237185
GRCh38: 14:28767979-28767979
18 FOXG1 NM_005249.5(FOXG1):c.730C>T (p.Arg244Cys) SNV Pathogenic 189620 rs786205009 GRCh37: 14:29237215-29237215
GRCh38: 14:28768009-28768009
19 FOXG1 NM_005249.5(FOXG1):c.788_792del (p.Asp263fs) Deletion Pathogenic 189621 rs786205010 GRCh37: 14:29237272-29237276
GRCh38: 14:28768066-28768070
20 FOXG1 NM_005249.5(FOXG1):c.969del (p.Ser323fs) Deletion Pathogenic 189622 rs786205011 GRCh37: 14:29237454-29237454
GRCh38: 14:28768248-28768248
21 FOXG1 NM_005249.5(FOXG1):c.821G>A (p.Arg274Gln) SNV Pathogenic 224139 rs869312700 GRCh37: 14:29237306-29237306
GRCh38: 14:28768100-28768100
22 FOXG1 NM_005249.5(FOXG1):c.500del (p.Glu167fs) Deletion Pathogenic 471469 rs1555321294 GRCh37: 14:29236985-29236985
GRCh38: 14:28767779-28767779
23 FOXG1 NM_005249.5(FOXG1):c.624C>A (p.Tyr208Ter) SNV Pathogenic 453289 rs267606826 GRCh37: 14:29237109-29237109
GRCh38: 14:28767903-28767903
24 FOXG1 , ARSJ t(4;14)(q26;q12) Translocation Pathogenic 426095 GRCh37: 4:114869960-114871254
GRCh38:
25 FOXG1 t(9;14)(q22.31;q12) Translocation Pathogenic 426096 GRCh37: 9:94269066-94269642
GRCh38:
26 FOXG1 , WDFY1 t(2;14)(q36.1;q12) Translocation Pathogenic 426094 GRCh37: 2:224764222-224765719
GRCh38:
27 FOXG1 NM_005249.5(FOXG1):c.946del (p.Leu316fs) Deletion Pathogenic 538818 rs1555321380 GRCh37: 14:29237429-29237429
GRCh38: 14:28768223-28768223
28 FOXG1 NM_005249.5(FOXG1):c.407_458del (p.Glu136fs) Deletion Pathogenic 579194 rs1566445169 GRCh37: 14:29236884-29236935
GRCh38: 14:28767678-28767729
29 FOXG1 NM_005249.5(FOXG1):c.1023C>G (p.Tyr341Ter) SNV Pathogenic 573079 rs764343290 GRCh37: 14:29237508-29237508
GRCh38: 14:28768302-28768302
30 FOXG1 NM_005249.5(FOXG1):c.762C>A (p.Tyr254Ter) SNV Pathogenic 651666 rs587783642 GRCh37: 14:29237247-29237247
GRCh38: 14:28768041-28768041
31 FOXG1 NM_005249.5(FOXG1):c.85del (p.Gln29fs) Deletion Pathogenic 803012 rs1594382746 GRCh37: 14:29236569-29236569
GRCh38: 14:28767363-28767363
32 FOXG1 NM_005249.5(FOXG1):c.301C>T (p.Gln101Ter) SNV Pathogenic 834510 GRCh37: 14:29236786-29236786
GRCh38: 14:28767580-28767580
33 FOXG1 NM_005249.5(FOXG1):c.1014dup (p.Met339fs) Duplication Pathogenic 836883 GRCh37: 14:29237495-29237496
GRCh38: 14:28768289-28768290
34 FOXG1 NM_005249.5(FOXG1):c.1414_1417del (p.Ser472fs) Deletion Pathogenic 855075 GRCh37: 14:29237896-29237899
GRCh38: 14:28768690-28768693
35 FOXG1 NC_000014.9:g.(?_28767260)_(28768769_?)del Deletion Pathogenic 830776 GRCh37: 14:29236466-29237975
GRCh38:
36 FOXG1 NM_005249.5(FOXG1):c.1135del (p.Leu379fs) Deletion Pathogenic 950543 GRCh37: 14:29237619-29237619
GRCh38: 14:28768413-28768413
37 FOXG1 NM_005249.5(FOXG1):c.406del (p.Glu136fs) Deletion Pathogenic 952981 GRCh37: 14:29236887-29236887
GRCh38: 14:28767681-28767681
38 FOXG1 NM_005249.5(FOXG1):c.590G>T (p.Ser197Ile) SNV Pathogenic 976112 GRCh37: 14:29237075-29237075
GRCh38: 14:28767869-28767869
39 FOXG1 NM_005249.5(FOXG1):c.632T>C (p.Ile211Thr) SNV Pathogenic 979179 GRCh37: 14:29237117-29237117
GRCh38: 14:28767911-28767911
40 FOXG1 NM_005249.5(FOXG1):c.506del (p.Gly169fs) Deletion Pathogenic 471470 rs1452295073 GRCh37: 14:29236986-29236986
GRCh38: 14:28767780-28767780
41 FOXG1 NM_005249.5(FOXG1):c.777del (p.Ser260fs) Deletion Pathogenic 807603 rs1594383798 GRCh37: 14:29237262-29237262
GRCh38: 14:28768056-28768056
42 FOXG1 NM_005249.5(FOXG1):c.624C>G (p.Tyr208Ter) SNV Pathogenic 13869 rs267606826 GRCh37: 14:29237109-29237109
GRCh38: 14:28767903-28767903
43 FOXG1 NM_005249.5(FOXG1):c.298del (p.Gln100fs) Deletion Pathogenic 158594 rs587783636 GRCh37: 14:29236779-29236779
GRCh38: 14:28767573-28767573
44 FOXG1 NM_005249.5(FOXG1):c.177_186dup (p.Pro63fs) Duplication Pathogenic 451937 rs1555321206 GRCh37: 14:29236655-29236656
GRCh38: 14:28767449-28767450
45 FOXG1 NM_005249.5(FOXG1):c.645C>G (p.Phe215Leu) SNV Pathogenic 373043 rs1057518165 GRCh37: 14:29237130-29237130
GRCh38: 14:28767924-28767924
46 FOXG1 NM_005249.5(FOXG1):c.406G>T (p.Glu136Ter) SNV Pathogenic 379607 rs1057520663 GRCh37: 14:29236891-29236891
GRCh38: 14:28767685-28767685
47 FOXG1 NM_005249.5(FOXG1):c.214C>T (p.Gln72Ter) SNV Pathogenic 487210 rs1555321237 GRCh37: 14:29236699-29236699
GRCh38: 14:28767493-28767493
48 FOXG1 NM_005249.5(FOXG1):c.460dup (p.Glu154fs) Duplication Pathogenic 95268 rs398124204 GRCh37: 14:29236938-29236939
GRCh38: 14:28767732-28767733
49 FOXG1 NM_005249.5(FOXG1):c.256dup (p.Gln86fs) Duplication Pathogenic 189613 rs786205001 GRCh37: 14:29236734-29236735
GRCh38: 14:28767528-28767529
50 FOXG1 NM_005249.5(FOXG1):c.256del (p.Gln86fs) Deletion Pathogenic 189612 rs786205001 GRCh37: 14:29236735-29236735
GRCh38: 14:28767529-28767529

UniProtKB/Swiss-Prot genetic disease variations for Rett Syndrome, Congenital Variant:

72
# Symbol AA change Variation ID SNP ID
1 FOXG1 p.Phe215Leu VAR_063885 rs267606828
2 FOXG1 p.Arg244Cys VAR_064396 rs786205009

Expression for Rett Syndrome, Congenital Variant

Search GEO for disease gene expression data for Rett Syndrome, Congenital Variant.

Pathways for Rett Syndrome, Congenital Variant

GO Terms for Rett Syndrome, Congenital Variant

Sources for Rett Syndrome, Congenital Variant

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