IHPRF3
MCID: HYP714
MIFTS: 31

Hypotonia, Infantile, with Psychomotor Retardation and Characteristic Facies 3 (IHPRF3)

Categories: Fetal diseases, Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Hypotonia, Infantile, with Psychomotor Retardation and...

MalaCards integrated aliases for Hypotonia, Infantile, with Psychomotor Retardation and Characteristic Facies 3:

Name: Hypotonia, Infantile, with Psychomotor Retardation and Characteristic Facies 3 57 72 29 6
Ihprf3 57 72
Hypotonia, Infantile, with Psychomotor Retardation and Characteristic Facies, Type 3 39
Tbck-Related Intellectual Disability Syndrome 58

Characteristics:

OMIM®:

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

Miscellaneous:
variable severity
onset at birth


HPO:

31
hypotonia, infantile, with psychomotor retardation and characteristic facies 3:
Inheritance autosomal recessive inheritance
Onset and clinical course variable expressivity congenital onset


Classifications:

Orphanet: 58  
Rare neurological diseases
Developmental anomalies during embryogenesis


Summaries for Hypotonia, Infantile, with Psychomotor Retardation and...

OMIM® : 57 Infantile hypotonia with psychomotor retardation and characteristic facies-3 is a severe autosomal recessive neurodevelopmental disorder with onset at birth or in early infancy. Most affected individuals show very poor, if any, normal psychomotor development, poor speech, and inability to walk independently (summary by Bhoj et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of infantile hypotonia with psychomotor retardation and characteristic facies, see IHPRF1 (615419). (616900) (Updated 05-Apr-2021)

MalaCards based summary : Hypotonia, Infantile, with Psychomotor Retardation and Characteristic Facies 3, also known as ihprf3, is related to alacrima, achalasia, and mental retardation syndrome and hypotonia. An important gene associated with Hypotonia, Infantile, with Psychomotor Retardation and Characteristic Facies 3 is TBCK (TBC1 Domain Containing Kinase). Affiliated tissues include eye, brain and skeletal muscle, and related phenotypes are neonatal hypotonia and severe muscular hypotonia

UniProtKB/Swiss-Prot : 72 Hypotonia, infantile, with psychomotor retardation and characteristic facies 3: An autosomal recessive neurodevelopmental disorder characterized by profound developmental disability, intellectual disability and severe hypotonia. Many patients have seizures, and show brain atrophy, dysgenesis of the corpus callosum and white-matter changes on neuroimaging. Non-specific facial dysmorphism is noted in some individuals.

Related Diseases for Hypotonia, Infantile, with Psychomotor Retardation and...

Diseases in the Hypotonia, Infantile, with Psychomotor Retardation and Characteristic Facies 3 family:

Hypotonia, Infantile, with Psychomotor Retardation and Characteristic Facies 1 Hypotonia, Infantile, with Psychomotor Retardation and Characteristic Facies 2

Diseases related to Hypotonia, Infantile, with Psychomotor Retardation and Characteristic Facies 3 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 alacrima, achalasia, and mental retardation syndrome 10.2
2 hypotonia 10.2

Symptoms & Phenotypes for Hypotonia, Infantile, with Psychomotor Retardation and...

Human phenotypes related to Hypotonia, Infantile, with Psychomotor Retardation and Characteristic Facies 3:

58 31 (show top 50) (show all 100)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 neonatal hypotonia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001319
2 severe muscular hypotonia 58 31 very rare (1%) Very frequent (99-80%) HP:0006829
3 progressive muscle weakness 58 31 hallmark (90%) Very frequent (99-80%) HP:0003323
4 emg: chronic denervation signs 58 31 hallmark (90%) Very frequent (99-80%) HP:0003444
5 respiratory insufficiency 58 31 frequent (33%) Frequent (79-30%) HP:0002093
6 coarse facial features 58 31 frequent (33%) Frequent (79-30%) HP:0000280
7 delayed speech and language development 58 31 very rare (1%) Frequent (79-30%) HP:0000750
8 skeletal muscle atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0003202
9 areflexia 58 31 frequent (33%) Frequent (79-30%) HP:0001284
10 ventriculomegaly 58 31 very rare (1%) Frequent (79-30%) HP:0002119
11 severe global developmental delay 58 31 frequent (33%) Frequent (79-30%) HP:0011344
12 hypoplasia of the corpus callosum 58 31 frequent (33%) Frequent (79-30%) HP:0002079
13 abnormality of the periventricular white matter 58 31 frequent (33%) Frequent (79-30%) HP:0002518
14 inability to walk 58 31 frequent (33%) Frequent (79-30%) HP:0002540
15 global brain atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0002283
16 multifocal seizures 58 31 frequent (33%) Frequent (79-30%) HP:0031165
17 abnormal circulating lipid concentration 31 frequent (33%) HP:0003119
18 macrocephaly 58 31 very rare (1%) Occasional (29-5%) HP:0000256
19 scoliosis 58 31 very rare (1%) Occasional (29-5%) HP:0002650
20 hypothermia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002045
21 hypothyroidism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000821
22 developmental regression 58 31 very rare (1%) Occasional (29-5%) HP:0002376
23 macroglossia 58 31 very rare (1%) Occasional (29-5%) HP:0000158
24 delayed skeletal maturation 58 31 occasional (7.5%) Occasional (29-5%) HP:0002750
25 thick eyebrow 58 31 occasional (7.5%) Occasional (29-5%) HP:0000574
26 cognitive impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0100543
27 osteoporosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0000939
28 high, narrow palate 58 31 occasional (7.5%) Occasional (29-5%) HP:0002705
29 epicanthus 58 31 very rare (1%) Occasional (29-5%) HP:0000286
30 pectus excavatum 58 31 occasional (7.5%) Occasional (29-5%) HP:0000767
31 bulbous nose 58 31 occasional (7.5%) Occasional (29-5%) HP:0000414
32 ventricular septal defect 58 31 occasional (7.5%) Occasional (29-5%) HP:0001629
33 broad forehead 58 31 occasional (7.5%) Occasional (29-5%) HP:0000337
34 tented upper lip vermilion 58 31 very rare (1%) Occasional (29-5%) HP:0010804
35 sloping forehead 58 31 very rare (1%) Occasional (29-5%) HP:0000340
36 hirsutism 58 31 occasional (7.5%) Occasional (29-5%) HP:0001007
37 limb undergrowth 58 31 occasional (7.5%) Occasional (29-5%) HP:0009826
38 emg: myokymic discharges 58 31 occasional (7.5%) Occasional (29-5%) HP:0100288
39 eeg with generalized epileptiform discharges 58 31 occasional (7.5%) Occasional (29-5%) HP:0011198
40 nystagmus 58 31 very rare (1%) Very rare (<4-1%) HP:0000639
41 short neck 58 31 very rare (1%) Very rare (<4-1%) HP:0000470
42 corneal opacity 58 31 very rare (1%) Very rare (<4-1%) HP:0007957
43 mandibular prognathia 58 31 very rare (1%) Very rare (<4-1%) HP:0000303
44 wide nasal bridge 58 31 very rare (1%) Very rare (<4-1%) HP:0000431
45 microcephaly 58 31 very rare (1%) Very rare (<4-1%) HP:0000252
46 sensorineural hearing impairment 58 31 very rare (1%) Very rare (<4-1%) HP:0000407
47 strabismus 58 31 very rare (1%) Very rare (<4-1%) HP:0000486
48 cryptorchidism 58 31 very rare (1%) Very rare (<4-1%) HP:0000028
49 autism 58 31 very rare (1%) Very rare (<4-1%) HP:0000717
50 upslanted palpebral fissure 58 31 very rare (1%) Very rare (<4-1%) HP:0000582

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
seizures
developmental regression
cerebellar hypoplasia
cerebral atrophy
poor speech
more
Head And Neck Nose:
anteverted nares
bulbous nose
high nasal bridge

Head And Neck Face:
sloping forehead
coarse facies
bitemporal narrowing

Muscle Soft Tissue:
hypotonia, severe

Respiratory:
respiratory insufficiency due to hypotonia

Head And Neck Mouth:
macroglossia
thick lips
gingival hyperplasia
tented upper lip

Neurologic Peripheral Nervous System:
hyporeflexia

Head And Neck Eyes:
deep-set eyes
arched eyebrows
cortical visual impairment

Head And Neck Head:
macrocephaly (in some patients)

Abdomen Gastrointestinal:
feeding difficulties due to hypotonia

Clinical features from OMIM®:

616900 (Updated 05-Apr-2021)

Drugs & Therapeutics for Hypotonia, Infantile, with Psychomotor Retardation and...

Search Clinical Trials , NIH Clinical Center for Hypotonia, Infantile, with Psychomotor Retardation and Characteristic Facies 3

Genetic Tests for Hypotonia, Infantile, with Psychomotor Retardation and...

Genetic tests related to Hypotonia, Infantile, with Psychomotor Retardation and Characteristic Facies 3:

# Genetic test Affiliating Genes
1 Hypotonia, Infantile, with Psychomotor Retardation and Characteristic Facies 3 29 TBCK

Anatomical Context for Hypotonia, Infantile, with Psychomotor Retardation and...

MalaCards organs/tissues related to Hypotonia, Infantile, with Psychomotor Retardation and Characteristic Facies 3:

40
Eye, Brain, Skeletal Muscle

Publications for Hypotonia, Infantile, with Psychomotor Retardation and...

Articles related to Hypotonia, Infantile, with Psychomotor Retardation and Characteristic Facies 3:

# Title Authors PMID Year
1
Recessive Inactivating Mutations in TBCK, Encoding a Rab GTPase-Activating Protein, Cause Severe Infantile Syndromic Encephalopathy. 57 6
27040692 2016
2
Mutations in TBCK, Encoding TBC1-Domain-Containing Kinase, Lead to a Recognizable Syndrome of Intellectual Disability and Hypotonia. 6 57
27040691 2016
3
Accelerating novel candidate gene discovery in neurogenetic disorders via whole-exome sequencing of prescreened multiplex consanguineous families. 57 6
25558065 2015
4
CNVs cause autosomal recessive genetic diseases with or without involvement of SNV/indels. 6
32576985 2020
5
Homozygous boricua TBCK mutation causes neurodegeneration and aberrant autophagy. 6
29283439 2018
6
TBCK influences cell proliferation, cell size and mTOR signaling pathway. 6
23977024 2013
7
Further delineation of TBCK - Infantile hypotonia with psychomotor retardation and characteristic facies type 3. 61
30103036 2019

Variations for Hypotonia, Infantile, with Psychomotor Retardation and...

ClinVar genetic disease variations for Hypotonia, Infantile, with Psychomotor Retardation and Characteristic Facies 3:

6 (show all 44)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 TBCK GRCh37/hg19 4q24(chr4:107092252-107092428) copy number loss Pathogenic 915974 GRCh37: 4:107092252-107092428
GRCh38:
2 TBCK Deletion Pathogenic 978028 GRCh37:
GRCh38: 4:106170668-106178063
3 TBCK NM_001163435.3(TBCK):c.1370del (p.Asn457fs) Deletion Pathogenic 225241 rs746860249 GRCh37: 4:107156505-107156505
GRCh38: 4:106235348-106235348
4 TBCK NC_000004.12:g.106168703_106217941del Deletion Pathogenic 977748 GRCh37:
GRCh38:
5 TBCK NM_001163435.3(TBCK):c.1532G>A (p.Arg511His) SNV Pathogenic 225237 rs869320711 GRCh37: 4:107154202-107154202
GRCh38: 4:106233045-106233045
6 TBCK NM_001163435.3(TBCK):c.2060_2235+1del Deletion Pathogenic 584451 rs1560755661 GRCh37: 4:107092251-107092427
GRCh38: 4:106171094-106171270
7 TBCK NM_001163435.3(TBCK):c.1860+1G>A SNV Pathogenic 636243 rs1303851095 GRCh37: 4:107133906-107133906
GRCh38: 4:106212749-106212749
8 TBCK NM_001163435.3(TBCK):c.659-1G>A SNV Pathogenic 638592 rs1579391376 GRCh37: 4:107170140-107170140
GRCh38: 4:106248983-106248983
9 TBCK NM_001163435.3(TBCK):c.193+1G>T SNV Pathogenic 984709 GRCh37: 4:107229924-107229924
GRCh38: 4:106308767-106308767
10 TBCK NM_001163435.3(TBCK):c.2143C>T (p.Gln715Ter) SNV Pathogenic 976465 GRCh37: 4:107092344-107092344
GRCh38: 4:106171187-106171187
11 TBCK NM_001163435.3(TBCK):c.1880T>G (p.Phe627Cys) SNV Pathogenic 807702 rs1579198426 GRCh37: 4:107115892-107115892
GRCh38: 4:106194735-106194735
12 TBCK NM_001163435.3(TBCK):c.1878G>T (p.Trp626Cys) SNV Pathogenic 807703 rs1579198447 GRCh37: 4:107115894-107115894
GRCh38: 4:106194737-106194737
13 TBCK NM_001163435.3(TBCK):c.831_832insTA (p.Pro278fs) Insertion Pathogenic 225238 rs869320769 GRCh37: 4:107168395-107168396
GRCh38: 4:106247238-106247239
14 TBCK NM_001163435.3(TBCK):c.1363A>T (p.Lys455Ter) SNV Pathogenic 225236 rs376699648 GRCh37: 4:107156512-107156512
GRCh38: 4:106235355-106235355
15 TBCK NM_001163435.3(TBCK):c.803_806del (p.Met268fs) Deletion Pathogenic 225240 rs771481304 GRCh37: 4:107168421-107168424
GRCh38: 4:106247264-106247267
16 TBCK NM_001163435.3(TBCK):c.1771C>T (p.Gln591Ter) SNV Pathogenic 373291 rs1057518332 GRCh37: 4:107151523-107151523
GRCh38: 4:106230366-106230366
17 TBCK NM_001163435.3(TBCK):c.376C>T (p.Arg126Ter) SNV Pathogenic 225235 rs575822089 GRCh37: 4:107183260-107183260
GRCh38: 4:106262103-106262103
18 TBCK NM_001163435.3(TBCK):c.1897+1G>A SNV Pathogenic 183338 rs374319146 GRCh37: 4:107115874-107115874
GRCh38: 4:106194717-106194717
19 TBCK NM_001163435.3(TBCK):c.381+1G>A SNV Pathogenic 1033752 GRCh37: 4:107183254-107183254
GRCh38: 4:106262097-106262097
20 TBCK NM_001163435.3(TBCK):c.531dup (p.Pro178fs) Duplication Likely pathogenic 1033753 GRCh37: 4:107173088-107173089
GRCh38: 4:106251931-106251932
21 TBCK NM_001163435.3(TBCK):c.2159C>T (p.Ser720Phe) SNV Likely pathogenic 915385 GRCh37: 4:107092328-107092328
GRCh38: 4:106171171-106171171
22 TBCK NM_001163435.3(TBCK):c.1351-1G>A SNV Likely pathogenic 932113 GRCh37: 4:107156525-107156525
GRCh38: 4:106235368-106235368
23 TBCK NM_001163435.3(TBCK):c.1584dup (p.Arg529Ter) Duplication Likely pathogenic 977525 GRCh37: 4:107154149-107154150
GRCh38: 4:106232992-106232993
24 TBCK NM_001163435.3(TBCK):c.456-2A>G SNV Likely pathogenic 977749 GRCh37: 4:107173166-107173166
GRCh38: 4:106252009-106252009
25 TBCK NM_001163435.3(TBCK):c.720+1G>A SNV Likely pathogenic 985890 GRCh37: 4:107170077-107170077
GRCh38: 4:106248920-106248920
26 TBCK NM_001163435.3(TBCK):c.1876_1892delinsATGCCA (p.Trp626fs) Indel Likely pathogenic 1029171 GRCh37: 4:107115880-107115896
GRCh38: 4:106194723-106194739
27 TBCK NM_001163435.3(TBCK):c.1170+1G>A SNV Likely pathogenic 974885 GRCh37: 4:107163626-107163626
GRCh38: 4:106242469-106242469
28 TBCK NM_001163435.3(TBCK):c.1854del (p.Pro619fs) Deletion Likely pathogenic 804443 rs1579257340 GRCh37: 4:107133913-107133913
GRCh38: 4:106212756-106212756
29 TBCK NM_001163435.3(TBCK):c.360_363del (p.His120fs) Deletion Likely pathogenic 587548 rs1560929669 GRCh37: 4:107183273-107183276
GRCh38: 4:106262116-106262119
30 TBCK NM_001163435.2(TBCK):c.2060-9050_2235+26133del35359 Deletion Likely pathogenic 638602 GRCh37: 4:107066118-107101467
GRCh38:
31 TBCK NM_001163435.3(TBCK):c.2060-2A>G SNV Likely pathogenic 225239 rs62321379 GRCh37: 4:107092429-107092429
GRCh38: 4:106171272-106171272
32 TBCK NM_001163435.3(TBCK):c.783G>T (p.Arg261Ser) SNV Uncertain significance 431722 rs1476004978 GRCh37: 4:107168444-107168444
GRCh38: 4:106247287-106247287
33 TBCK NM_001163435.3(TBCK):c.1804G>A (p.Ala602Thr) SNV Uncertain significance 638385 rs150221832 GRCh37: 4:107133963-107133963
GRCh38: 4:106212806-106212806
34 TBCK NM_001163435.3(TBCK):c.1322G>A (p.Arg441Lys) SNV Uncertain significance 811423 rs1579346494 GRCh37: 4:107157575-107157575
GRCh38: 4:106236418-106236418
35 TBCK NM_001163435.3(TBCK):c.2088A>C (p.Glu696Asp) SNV Uncertain significance 1029172 GRCh37: 4:107092399-107092399
GRCh38: 4:106171242-106171242
36 TBCK NM_001163435.3(TBCK):c.2370T>G (p.Ser790Arg) SNV Uncertain significance 1029173 GRCh37: 4:107037401-107037401
GRCh38: 4:106116244-106116244
37 TBCK NM_001163435.3(TBCK):c.2420G>C (p.Arg807Pro) SNV Uncertain significance 1029174 GRCh37: 4:107016790-107016790
GRCh38: 4:106095633-106095633
38 TBCK NM_001163435.3(TBCK):c.2428A>G (p.Ile810Val) SNV Uncertain significance 1029175 GRCh37: 4:107016782-107016782
GRCh38: 4:106095625-106095625
39 TBCK NM_001163435.3(TBCK):c.454G>C (p.Gly152Arg) SNV Uncertain significance 1029176 GRCh37: 4:107181595-107181595
GRCh38: 4:106260438-106260438
40 TBCK NM_001163435.3(TBCK):c.1162C>A (p.Leu388Ile) SNV Uncertain significance 1033749 GRCh37: 4:107163635-107163635
GRCh38: 4:106242478-106242478
41 TBCK NM_001163435.3(TBCK):c.1220+5G>A SNV Uncertain significance 1033750 GRCh37: 4:107157911-107157911
GRCh38: 4:106236754-106236754
42 TBCK NM_001163435.3(TBCK):c.2284C>T (p.Arg762Trp) SNV Uncertain significance 1033751 GRCh37: 4:107037487-107037487
GRCh38: 4:106116330-106116330
43 TBCK NM_001163435.3(TBCK):c.658+4A>G SNV Uncertain significance 1033754 GRCh37: 4:107171571-107171571
GRCh38: 4:106250414-106250414
44 TBCK NM_001163435.3(TBCK):c.796C>G (p.Gln266Glu) SNV Benign 802081 rs3775091 GRCh37: 4:107168431-107168431
GRCh38: 4:106247274-106247274

UniProtKB/Swiss-Prot genetic disease variations for Hypotonia, Infantile, with Psychomotor Retardation and Characteristic Facies 3:

72
# Symbol AA change Variation ID SNP ID
1 TBCK p.Arg511His VAR_077816 rs869320711
2 TBCK p.Leu551Pro VAR_077817

Expression for Hypotonia, Infantile, with Psychomotor Retardation and...

Search GEO for disease gene expression data for Hypotonia, Infantile, with Psychomotor Retardation and Characteristic Facies 3.

Pathways for Hypotonia, Infantile, with Psychomotor Retardation and...

GO Terms for Hypotonia, Infantile, with Psychomotor Retardation and...

Sources for Hypotonia, Infantile, with Psychomotor Retardation and...

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
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39 LOVD
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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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