MCID: HYP638
MIFTS: 32

Hypotonia-Speech Impairment-Severe Cognitive Delay Syndrome

Categories: Fetal diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Hypotonia-Speech Impairment-Severe Cognitive Delay Syndrome

MalaCards integrated aliases for Hypotonia-Speech Impairment-Severe Cognitive Delay Syndrome:

Name: Hypotonia-Speech Impairment-Severe Cognitive Delay Syndrome 58 6
Hypotonia, Infantile, with Psychomotor Retardation and Characteristic Facies 39
Infantile Hypotonia-Psychomotor Retardation-Characteristic Facies Syndrome 58
Infantile Hypotonia with Psychomotor Retardation and Characteristic Facies 36
Ihprf Syndrome 58

Characteristics:

Orphanet epidemiological data:

58
hypotonia-speech impairment-severe cognitive delay syndrome
Age of onset: Infancy,Neonatal; Age of death: adolescent,late childhood;

Classifications:

Orphanet: 58  
Rare neurological diseases
Developmental anomalies during embryogenesis


Summaries for Hypotonia-Speech Impairment-Severe Cognitive Delay Syndrome

KEGG : 36 Infantile hypotonia with psychomotor retardation and characteristic facies (IHPRF) is an autosomal-recessive syndrome characterized by subtle facial dysmorphism, variable degrees of hypotonia, speech impairment, chronic constipation, and intellectual disability. It is caused by mutations in the cation channel NALCN and UNC80. NALCN has a role in basal sodium ion leak conductance in neurons, essential for neuronal function. UNC80 bridges between UNC79 and NALCN. Recently, pathogenic biallelic variants in TBC1-domain-containing kinase (TBCK) were also identified.

MalaCards based summary : Hypotonia-Speech Impairment-Severe Cognitive Delay Syndrome, also known as hypotonia, infantile, with psychomotor retardation and characteristic facies, is related to infantile hypotonia and hypotonia. An important gene associated with Hypotonia-Speech Impairment-Severe Cognitive Delay Syndrome is UNC80 (Unc-80 Homolog, NALCN Channel Complex Subunit), and among its related pathways/superpathways is Ion channel transport. Related phenotypes are global developmental delay and intellectual disability, severe

Related Diseases for Hypotonia-Speech Impairment-Severe Cognitive Delay Syndrome

Graphical network of the top 20 diseases related to Hypotonia-Speech Impairment-Severe Cognitive Delay Syndrome:



Diseases related to Hypotonia-Speech Impairment-Severe Cognitive Delay Syndrome

Symptoms & Phenotypes for Hypotonia-Speech Impairment-Severe Cognitive Delay Syndrome

Human phenotypes related to Hypotonia-Speech Impairment-Severe Cognitive Delay Syndrome:

58 31 (show top 50) (show all 56)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 global developmental delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0001263
2 intellectual disability, severe 58 31 hallmark (90%) Very frequent (99-80%) HP:0010864
3 absent speech 58 31 hallmark (90%) Very frequent (99-80%) HP:0001344
4 motor delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0001270
5 esotropia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000565
6 infantile muscular hypotonia 58 31 hallmark (90%) Very frequent (99-80%) HP:0008947
7 tapered distal phalanges of finger 58 31 hallmark (90%) Very frequent (99-80%) HP:0009884
8 frontal bossing 58 31 frequent (33%) Frequent (79-30%) HP:0002007
9 eeg abnormality 58 31 frequent (33%) Frequent (79-30%) HP:0002353
10 scoliosis 58 31 frequent (33%) Frequent (79-30%) HP:0002650
11 constipation 58 31 frequent (33%) Frequent (79-30%) HP:0002019
12 wide nasal bridge 58 31 frequent (33%) Frequent (79-30%) HP:0000431
13 dyskinesia 58 31 frequent (33%) Frequent (79-30%) HP:0100660
14 microcephaly 58 31 frequent (33%) Frequent (79-30%) HP:0000252
15 smooth philtrum 58 31 frequent (33%) Frequent (79-30%) HP:0000319
16 anteverted nares 58 31 frequent (33%) Frequent (79-30%) HP:0000463
17 neonatal hypotonia 58 31 frequent (33%) Frequent (79-30%) HP:0001319
18 short stature 58 31 frequent (33%) Frequent (79-30%) HP:0004322
19 micrognathia 58 31 frequent (33%) Frequent (79-30%) HP:0000347
20 talipes equinovarus 58 31 frequent (33%) Frequent (79-30%) HP:0001762
21 arachnodactyly 58 31 frequent (33%) Frequent (79-30%) HP:0001166
22 downslanted palpebral fissures 58 31 frequent (33%) Frequent (79-30%) HP:0000494
23 cachexia 58 31 frequent (33%) Frequent (79-30%) HP:0004326
24 low-set, posteriorly rotated ears 58 31 frequent (33%) Frequent (79-30%) HP:0000368
25 thin upper lip vermilion 58 31 frequent (33%) Frequent (79-30%) HP:0000219
26 prominent nasal bridge 58 31 frequent (33%) Frequent (79-30%) HP:0000426
27 short philtrum 58 31 frequent (33%) Frequent (79-30%) HP:0000322
28 small hand 58 31 frequent (33%) Frequent (79-30%) HP:0200055
29 triangular face 58 31 frequent (33%) Frequent (79-30%) HP:0000325
30 tented upper lip vermilion 58 31 frequent (33%) Frequent (79-30%) HP:0010804
31 plagiocephaly 58 31 frequent (33%) Frequent (79-30%) HP:0001357
32 hyperesthesia 58 31 frequent (33%) Frequent (79-30%) HP:0100963
33 severe failure to thrive 58 31 frequent (33%) Frequent (79-30%) HP:0001525
34 enlarged naris 58 31 frequent (33%) Frequent (79-30%) HP:0009931
35 seizure 31 frequent (33%) HP:0001250
36 nystagmus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000639
37 short neck 58 31 occasional (7.5%) Occasional (29-5%) HP:0000470
38 self-injurious behavior 58 31 occasional (7.5%) Occasional (29-5%) HP:0100716
39 spastic tetraplegia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002510
40 intrauterine growth retardation 58 31 occasional (7.5%) Occasional (29-5%) HP:0001511
41 elbow flexion contracture 58 31 occasional (7.5%) Occasional (29-5%) HP:0002987
42 emg: myopathic abnormalities 58 31 occasional (7.5%) Occasional (29-5%) HP:0003458
43 hip contracture 58 31 occasional (7.5%) Occasional (29-5%) HP:0003273
44 hypoplasia of the corpus callosum 58 31 occasional (7.5%) Occasional (29-5%) HP:0002079
45 knee flexion contracture 58 31 occasional (7.5%) Occasional (29-5%) HP:0006380
46 obstructive sleep apnea 58 31 occasional (7.5%) Occasional (29-5%) HP:0002870
47 muscular hypotonia of the trunk 58 31 occasional (7.5%) Occasional (29-5%) HP:0008936
48 conspicuously happy disposition 58 31 occasional (7.5%) Occasional (29-5%) HP:0100024
49 nasogastric tube feeding in infancy 58 31 occasional (7.5%) Occasional (29-5%) HP:0011470
50 seizures 58 Frequent (79-30%)

Drugs & Therapeutics for Hypotonia-Speech Impairment-Severe Cognitive Delay Syndrome

Search Clinical Trials , NIH Clinical Center for Hypotonia-Speech Impairment-Severe Cognitive Delay Syndrome

Genetic Tests for Hypotonia-Speech Impairment-Severe Cognitive Delay Syndrome

Anatomical Context for Hypotonia-Speech Impairment-Severe Cognitive Delay Syndrome

Publications for Hypotonia-Speech Impairment-Severe Cognitive Delay Syndrome

Articles related to Hypotonia-Speech Impairment-Severe Cognitive Delay Syndrome:

(show all 16)
# Title Authors PMID Year
1
Biallelic Mutations in UNC80 Cause Persistent Hypotonia, Encephalopathy, Growth Retardation, and Severe Intellectual Disability. 6 61
26708751 2016
2
Genetic variants in components of the NALCN-UNC80-UNC79 ion channel complex cause a broad clinical phenotype (NALCN channelopathies). 6
30167850 2018
3
UNC80 mutation causes a syndrome of hypotonia, severe intellectual disability, dyskinesia and dysmorphism, similar to that caused by mutations in its interacting cation channel NALCN. 6
26545877 2016
4
Mutations in UNC80, Encoding Part of the UNC79-UNC80-NALCN Channel Complex, Cause Autosomal-Recessive Severe Infantile Encephalopathy. 6
26708753 2016
5
Mutations in NALCN cause an autosomal-recessive syndrome with severe hypotonia, speech impairment, and cognitive delay. 6
24075186 2013
6
Recessive truncating NALCN mutation in infantile neuroaxonal dystrophy with facial dysmorphism. 6
23749988 2013
7
Expanding the phenotype of PURA-related neurodevelopmental disorder: a close differential diagnosis of infantile hypotonia with psychomotor retardation and characteristic facies. 61
33229923 2021
8
A homozygous truncating NALCN variant in two Afro-Caribbean siblings with hypotonia and dolichocephaly. 61
32618095 2020
9
A Homozygous Truncating Mutation in NALCN Causing IHPRF1: Detailed Clinical Manifestations and a Review of Literature. 61
32943903 2020
10
Functional expression of CLIFAHDD and IHPRF pathogenic variants of the NALCN channel in neuronal cells reveals both gain- and loss-of-function properties. 61
31409833 2019
11
Whole exome sequencing revealed mutations in FBXL4, UNC80, and ADK in Thai patients with severe intellectual disabilities. 61
30771478 2019
12
Further delineation of TBCK - Infantile hypotonia with psychomotor retardation and characteristic facies type 3. 61
30103036 2019
13
Periodic breathing in patients with NALCN mutations. 61
29968795 2018
14
Biallelic UNC80 mutations caused infantile hypotonia with psychomotor retardation and characteristic facies 2 in two Chinese patients with variable phenotypes. 61
29572195 2018
15
Novel NALCN biallelic truncating mutations in siblings with IHPRF1 syndrome. 61
29399786 2018
16
Identification of a novel homozygous UNC80 variant in a child with infantile hypotonia with psychomotor retardation and characteristic facies-2 (IHPRF2). 61
29430593 2018

Variations for Hypotonia-Speech Impairment-Severe Cognitive Delay Syndrome

ClinVar genetic disease variations for Hypotonia-Speech Impairment-Severe Cognitive Delay Syndrome:

6 (show top 50) (show all 103)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 NALCN NM_052867.4(NALCN):c.3022C>T (p.Arg1008Ter) SNV Pathogenic 684699 rs766421214 GRCh37: 13:101755558-101755558
GRCh38: 13:101103207-101103207
2 NALCN NM_052867.4(NALCN):c.2629del (p.Gln877fs) Deletion Pathogenic 684700 rs1594212468 GRCh37: 13:101757252-101757252
GRCh38: 13:101104901-101104901
3 NALCN NM_052867.4(NALCN):c.3056dup (p.Leu1019fs) Duplication Pathogenic 684701 rs772394714 GRCh37: 13:101755523-101755524
GRCh38: 13:101103172-101103173
4 NALCN NM_052867.4(NALCN):c.4281C>A (p.Phe1427Leu) SNV Pathogenic 684702 rs1594134160 GRCh37: 13:101721096-101721096
GRCh38: 13:101068744-101068744
5 NALCN NM_052867.4(NALCN):c.4103+2T>C SNV Pathogenic 684703 rs1594146891 GRCh37: 13:101726863-101726863
GRCh38: 13:101074512-101074512
6 NALCN NM_052867.4(NALCN):c.3556C>T (p.Gln1186Ter) SNV Pathogenic 684704 rs1594168638 GRCh37: 13:101736089-101736089
GRCh38: 13:101083738-101083738
7 NALCN NM_052867.4(NALCN):c.2435dup (p.Glu813fs) Duplication Pathogenic 684705 rs1594218864 GRCh37: 13:101760069-101760070
GRCh38: 13:101107718-101107719
8 NALCN NM_052867.4(NALCN):c.4333A>T (p.Ile1445Leu) SNV Pathogenic 684706 rs1459166839 GRCh37: 13:101720383-101720383
GRCh38: 13:101068031-101068031
9 NALCN NM_052867.4(NALCN):c.2889+3_2889+6del Deletion Pathogenic 684707 rs1594211051 GRCh37: 13:101756640-101756643
GRCh38: 13:101104289-101104292
10 NALCN NM_052867.4(NALCN):c.4150C>T (p.Arg1384Ter) SNV Pathogenic 684708 rs1031314447 GRCh37: 13:101725983-101725983
GRCh38: 13:101073631-101073631
11 NALCN NM_052867.4(NALCN):c.321G>A (p.Trp107Ter) SNV Pathogenic 684709 rs1594761911 GRCh37: 13:102030975-102030975
GRCh38: 13:101378624-101378624
12 NALCN NM_052867.4(NALCN):c.2758del (p.Ile920fs) Deletion Pathogenic 684710 rs1594211334 GRCh37: 13:101756777-101756777
GRCh38: 13:101104426-101104426
13 NALCN NM_052867.4(NALCN):c.537del (p.Ile178_Trp179insTer) Deletion Pathogenic 684711 rs1594759803 GRCh37: 13:102029158-102029158
GRCh38: 13:101376807-101376807
14 UNC80 NM_032504.1(UNC80):c.8116C>T (p.Arg2706Ter) SNV Pathogenic 684712 rs1575183610 GRCh37: 2:210836982-210836982
GRCh38: 2:209972258-209972258
15 UNC80 NM_032504.1(UNC80):c.520C>T (p.Arg174Ter) SNV Pathogenic 684713 rs751913925 GRCh37: 2:210642203-210642203
GRCh38: 2:209777479-209777479
16 UNC80 NM_182587.4(UNC80):c.1679_1680AC[1] (p.Thr561fs) Microsatellite Pathogenic 684714 rs1574579609 GRCh37: 2:210682662-210682663
GRCh38: 2:209817938-209817939
17 UNC80 NM_032504.1(UNC80):c.5671C>T (p.Arg1891Ter) SNV Pathogenic 684715 rs1262654975 GRCh37: 2:210794657-210794657
GRCh38: 2:209929933-209929933
18 NALCN NM_052867.4(NALCN):c.1924C>T (p.Gln642Ter) SNV Pathogenic 65422 rs587777038 GRCh37: 13:101797163-101797163
GRCh38: 13:101144812-101144812
19 NALCN NM_052867.4(NALCN):c.1489del (p.Tyr497fs) Deletion Pathogenic 88686 rs869025188 GRCh37: 13:101881881-101881881
GRCh38: 13:101229530-101229530
20 NALCN NM_052867.4(NALCN):c.3860G>T (p.Trp1287Leu) SNV Pathogenic 88687 rs587777068 GRCh37: 13:101733903-101733903
GRCh38: 13:101081552-101081552
21 UNC80 NM_032504.1(UNC80):c.565G>A (p.Val189Met) SNV Pathogenic 219190 rs864321623 GRCh37: 2:210642248-210642248
GRCh38: 2:209777524-209777524
22 UNC80 NM_032504.1(UNC80):c.151C>T (p.Arg51Ter) SNV Pathogenic 222017 rs869025320 GRCh37: 2:210640622-210640622
GRCh38: 2:209775898-209775898
23 UNC80 NM_032504.1(UNC80):c.8573_8574del (p.Lys2858fs) Deletion Pathogenic 488633 rs1553621490 GRCh37: 2:210841026-210841027
GRCh38: 2:209976302-209976303
24 NALCN NM_052867.4(NALCN):c.3269G>A (p.Trp1090Ter) SNV Pathogenic 522637 rs1555379886 GRCh37: 13:101747925-101747925
GRCh38: 13:101095574-101095574
25 NALCN NM_052867.4(NALCN):c.4236C>A (p.Tyr1412Ter) SNV Pathogenic 522758 rs1158771233 GRCh37: 13:101721141-101721141
GRCh38: 13:101068789-101068789
26 UNC80 NM_032504.1(UNC80):c.601-1G>A SNV Pathogenic 684717 rs1574434743 GRCh37: 2:210650789-210650789
GRCh38: 2:209786065-209786065
27 UNC80 NM_001371986.1(UNC80):c.3358-1G>C SNV Pathogenic 801862 rs1186997983 GRCh37: 2:210707073-210707073
GRCh38: 2:209842349-209842349
28 UNC80 NM_001371986.1(UNC80):c.3853C>T (p.Arg1285Ter) SNV Pathogenic 801863 rs1574855486 GRCh37: 2:210742690-210742690
GRCh38: 2:209877966-209877966
29 NALCN NM_052867.4(NALCN):c.2563C>T (p.Arg855Ter) SNV Pathogenic 489164 rs376152742 GRCh37: 13:101759854-101759854
GRCh38: 13:101107503-101107503
30 NALCN NM_052867.4(NALCN):c.1434+1G>A SNV Pathogenic 915368 GRCh37: 13:101890105-101890105
GRCh38: 13:101237754-101237754
31 UNC80 NM_001371986.1(UNC80):c.6646+1del Deletion Pathogenic 976333 GRCh37: 2:210804376-210804376
GRCh38: 2:209939652-209939652
32 UNC80 NM_001371986.1(UNC80):c.1696C>T (p.Arg566Ter) SNV Pathogenic 1028448 GRCh37: 2:210683719-210683719
GRCh38: 2:209818995-209818995
33 UNC80 NM_001371986.1(UNC80):c.3042-1G>T SNV Pathogenic 1028452 GRCh37: 2:210703945-210703945
GRCh38: 2:209839221-209839221
34 UNC80 NM_032504.1(UNC80):c.1653_1654dup (p.Asp552fs) Duplication Pathogenic 545906 rs1553527439 GRCh37: 2:210682635-210682636
GRCh38: 2:209817911-209817912
35 UNC80 NM_032504.1(UNC80):c.4150G>T (p.Glu1384Ter) SNV Pathogenic 431144 rs981874506 GRCh37: 2:210752852-210752852
GRCh38: 2:209888128-209888128
36 UNC80 NM_032504.1(UNC80):c.2399del (p.Leu800fs) Deletion Pathogenic 431143 rs1135401813 GRCh37: 2:210690696-210690696
GRCh38: 2:209825972-209825972
37 UNC80 NM_032504.1(UNC80):c.1078C>T (p.Arg360Ter) SNV Pathogenic/Likely pathogenic 219189 rs200659479 GRCh37: 2:210678443-210678443
GRCh38: 2:209813719-209813719
38 UNC80 NM_032504.1(UNC80):c.6607G>A (p.Asp2203Asn) SNV Likely pathogenic 268208 rs886041094 GRCh37: 2:210806103-210806103
GRCh38: 2:209941379-209941379
39 UNC80 NM_032504.1(UNC80):c.8574+2T>G SNV Likely pathogenic 453302 rs1553621496 GRCh37: 2:210841029-210841029
GRCh38: 2:209976305-209976305
40 UNC80 NM_032504.1(UNC80):c.3793C>T (p.Arg1265Ter) SNV Likely pathogenic 219188 rs864321622 GRCh37: 2:210737641-210737641
GRCh38: 2:209872917-209872917
41 NALCN NM_052867.4(NALCN):c.4755+1G>T SNV Likely pathogenic 522142 rs1158141270 GRCh37: 13:101714319-101714319
GRCh38: 13:101061967-101061967
42 UNC80 NM_032504.1(UNC80):c.8058+2T>G SNV Likely pathogenic 684716 rs1575179679 GRCh37: 2:210835683-210835683
GRCh38: 2:209970959-209970959
43 UNC80 NM_032504.1(UNC80):c.1513C>T (p.Arg505Ter) SNV Likely pathogenic 505011 rs767633598 GRCh37: 2:210681810-210681810
GRCh38: 2:209817086-209817086
44 UNC80 NM_001371986.1(UNC80):c.409C>T (p.Arg137Ter) SNV Likely pathogenic 993028 GRCh37: 2:210642092-210642092
GRCh38: 2:209777368-209777368
45 NALCN NM_052867.4(NALCN):c.638del (p.Lys213fs) Deletion Likely pathogenic 996877 GRCh37: 13:102029057-102029057
GRCh38: 13:101376706-101376706
46 NALCN NM_052867.4(NALCN):c.2579+5G>A SNV Likely pathogenic 870580 GRCh37: 13:101759833-101759833
GRCh38: 13:101107482-101107482
47 NALCN NM_052867.4(NALCN):c.2671del (p.Val891fs) Deletion Likely pathogenic 813894 rs1594211911 GRCh37: 13:101756967-101756967
GRCh38: 13:101104616-101104616
48 UNC80 NM_001371986.1(UNC80):c.1357del (p.Arg453fs) Deletion Likely pathogenic 829816 rs1574574226 GRCh37: 2:210681653-210681653
GRCh38: 2:209816929-209816929
49 UNC80 NM_001371986.1(UNC80):c.7700_7701del (p.Thr2567fs) Deletion Likely pathogenic 829817 rs1575147319 GRCh37: 2:210824326-210824327
GRCh38: 2:209959602-209959603
50 NALCN NM_052867.4(NALCN):c.2831dup (p.Thr945fs) Duplication Likely pathogenic 800865 rs1594211244 GRCh37: 13:101756703-101756704
GRCh38: 13:101104352-101104353

Expression for Hypotonia-Speech Impairment-Severe Cognitive Delay Syndrome

Search GEO for disease gene expression data for Hypotonia-Speech Impairment-Severe Cognitive Delay Syndrome.

Pathways for Hypotonia-Speech Impairment-Severe Cognitive Delay Syndrome

Pathways related to Hypotonia-Speech Impairment-Severe Cognitive Delay Syndrome according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.12 UNC80 NALCN

GO Terms for Hypotonia-Speech Impairment-Severe Cognitive Delay Syndrome

Biological processes related to Hypotonia-Speech Impairment-Severe Cognitive Delay Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ion transmembrane transport GO:0034220 8.96 UNC80 NALCN
2 cation transmembrane transport GO:0098655 8.62 UNC80 NALCN

Molecular functions related to Hypotonia-Speech Impairment-Severe Cognitive Delay Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cation channel activity GO:0005261 8.62 UNC80 NALCN

Sources for Hypotonia-Speech Impairment-Severe Cognitive Delay 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 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
Content
Loading form....