IHPRF1
MCID: HYP723
MIFTS: 31

Hypotonia, Infantile, with Psychomotor Retardation and Characteristic Facies 1 (IHPRF1)

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 1:

Name: Hypotonia, Infantile, with Psychomotor Retardation and Characteristic Facies 1 57 72 29 6
Ihprf1 57 72
Ihprf 57 72
Hypotonia, Infantile, with Psychomotor Retardation and Characteristic Facies, Type 1 39
Hypotonia, Infantile, with Psychomotor Retardation and Characteristic Facies 70
Infantile Neuroaxonal Neurodegeneration with Facial Dysmophism 72
Innfd 72

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive

Miscellaneous:
progressive disorder
onset at birth or in infancy
some patients never achieve sitting


HPO:

31
hypotonia, infantile, with psychomotor retardation and characteristic facies 1:
Inheritance autosomal recessive inheritance
Onset and clinical course progressive


Classifications:



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

UniProtKB/Swiss-Prot : 72 Hypotonia, infantile, with psychomotor retardation and characteristic facies 1: A neurodegenerative disease characterized by variable degrees of hypotonia, speech impairment, intellectual disability, pyramidal signs, subtle facial dysmorphism, and chronic constipation. Some patients manifest neuroaxonal dystrophy, optic atrophy, unmyelinated axons and spheroid bodies in tissue biopsies.

MalaCards based summary : Hypotonia, Infantile, with Psychomotor Retardation and Characteristic Facies 1, also known as ihprf1, is related to congenital contractures of the limbs and face, hypotonia, and developmental delay and congenital contractures, and has symptoms including constipation and abnormal pyramidal signs. An important gene associated with Hypotonia, Infantile, with Psychomotor Retardation and Characteristic Facies 1 is NALCN (Sodium Leak Channel, Non-Selective). Affiliated tissues include eye and skeletal muscle, and related phenotypes are hyperreflexia and scoliosis

OMIM® : 57 Infantile hypotonia with psychomotor retardation and characteristic facies (IHPRF) is a severe autosomal recessive neurologic disorder with onset at birth or in early infancy. Affected individuals show very poor, if any, normal cognitive development. Some patients are never learn to sit or walk independently (summary by Al-Sayed et al., 2013). (615419) (Updated 20-May-2021)

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

Graphical network of the top 20 diseases related to Hypotonia, Infantile, with Psychomotor Retardation and Characteristic Facies 1:



Diseases related to Hypotonia, Infantile, with Psychomotor Retardation and Characteristic Facies 1

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

Human phenotypes related to Hypotonia, Infantile, with Psychomotor Retardation and Characteristic Facies 1:

31 (show all 33)
# Description HPO Frequency HPO Source Accession
1 hyperreflexia 31 HP:0001347
2 scoliosis 31 HP:0002650
3 abnormal pyramidal sign 31 HP:0007256
4 nystagmus 31 HP:0000639
5 constipation 31 HP:0002019
6 global developmental delay 31 HP:0001263
7 macrotia 31 HP:0000400
8 pectus carinatum 31 HP:0000768
9 short nose 31 HP:0003196
10 microcephaly 31 HP:0000252
11 smooth philtrum 31 HP:0000319
12 optic atrophy 31 HP:0000648
13 gastroesophageal reflux 31 HP:0002020
14 brachycephaly 31 HP:0000248
15 spastic tetraplegia 31 HP:0002510
16 prominent forehead 31 HP:0011220
17 skeletal muscle atrophy 31 HP:0003202
18 strabismus 31 HP:0000486
19 cryptorchidism 31 HP:0000028
20 postnatal growth retardation 31 HP:0008897
21 micrognathia 31 HP:0000347
22 low-set ears 31 HP:0000369
23 wide mouth 31 HP:0000154
24 thin upper lip vermilion 31 HP:0000219
25 decreased motor nerve conduction velocity 31 HP:0003431
26 triangular face 31 HP:0000325
27 poor eye contact 31 HP:0000817
28 feeding difficulties 31 HP:0011968
29 psychomotor retardation 31 HP:0025356
30 muscular hypotonia of the trunk 31 HP:0008936
31 poor speech 31 HP:0002465
32 slender nose 31 HP:0000417
33 seizure 31 HP:0001250

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Neurologic Central Nervous System:
hyperreflexia
spastic tetraplegia
pyramidal signs
seizures (in some patients)
truncal hypotonia
more
Head And Neck Eyes:
nystagmus
strabismus
poor eye contact
optic atrophy (in some patients)

Chest External Features:
pectus carinatum

Head And Neck Face:
smooth philtrum
prominent forehead
micrognathia
triangular face

Head And Neck Ears:
low-set ears
large ears

Head And Neck Nose:
slender nose

Skeletal Feet:
pes varus

Neurologic Peripheral Nervous System:
neuroaxonal dystrophy (in some patients)
sural nerve biopsy shows unmyelinated axons (in some patients)
spheroid formation (in some patients)
sural nerve edema (in some patients)
decreased motor nerve conduction velocity (in some patients)

Skeletal Spine:
scoliosis

Abdomen Gastrointestinal:
constipation
gastroesophageal reflux
poor feeding

Head And Neck Head:
microcephaly
brachycephaly

Genitourinary Internal Genitalia Male:
cryptorchidism

Head And Neck Mouth:
wide mouth
thin upper lip

Muscle Soft Tissue:
muscle atrophy
hypotonia, infantile, severe

Growth Other:
postnatal growth retardation (in some patients)

Clinical features from OMIM®:

615419 (Updated 20-May-2021)

UMLS symptoms related to Hypotonia, Infantile, with Psychomotor Retardation and Characteristic Facies 1:


constipation; abnormal pyramidal signs

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

Search Clinical Trials , NIH Clinical Center for Hypotonia, Infantile, with Psychomotor Retardation and Characteristic Facies 1

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

Genetic tests related to Hypotonia, Infantile, with Psychomotor Retardation and Characteristic Facies 1:

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

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

MalaCards organs/tissues related to Hypotonia, Infantile, with Psychomotor Retardation and Characteristic Facies 1:

40
Eye, Skeletal Muscle

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

Articles related to Hypotonia, Infantile, with Psychomotor Retardation and Characteristic Facies 1:

# Title Authors PMID Year
1
Mutations in NALCN cause an autosomal-recessive syndrome with severe hypotonia, speech impairment, and cognitive delay. 6 57
24075186 2013
2
Recessive truncating NALCN mutation in infantile neuroaxonal dystrophy with facial dysmorphism. 57 6
23749988 2013
3
Genetic variants in components of the NALCN-UNC80-UNC79 ion channel complex cause a broad clinical phenotype (NALCN channelopathies). 61 6
30167850 2018
4
Dysmorphic face in two siblings with infantile neuroaxonal dystrophy. 57
12558119 2002
5
A homozygous truncating NALCN variant in two Afro-Caribbean siblings with hypotonia and dolichocephaly. 61
32618095 2020
6
A Homozygous Truncating Mutation in NALCN Causing IHPRF1: Detailed Clinical Manifestations and a Review of Literature. 61
32943903 2020
7
Periodic breathing in patients with NALCN mutations. 61
29968795 2018
8
Novel NALCN biallelic truncating mutations in siblings with IHPRF1 syndrome. 61
29399786 2018
9
Biallelic mutations in NALCN: Expanding the genotypic and phenotypic spectra of IHPRF1. 61
29168298 2018

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

ClinVar genetic disease variations for Hypotonia, Infantile, with Psychomotor Retardation and Characteristic Facies 1:

6 (show all 34)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 NALCN NM_052867.4(NALCN):c.1924C>T (p.Gln642Ter) SNV Pathogenic 65422 rs587777038 GRCh37: 13:101797163-101797163
GRCh38: 13:101144812-101144812
2 NALCN NM_052867.4(NALCN):c.3269G>A (p.Trp1090Ter) SNV Pathogenic 522637 rs1555379886 GRCh37: 13:101747925-101747925
GRCh38: 13:101095574-101095574
3 NALCN NM_052867.4(NALCN):c.4236C>A (p.Tyr1412Ter) SNV Pathogenic 522758 rs1158771233 GRCh37: 13:101721141-101721141
GRCh38: 13:101068789-101068789
4 NALCN NM_052867.4(NALCN):c.1434+1G>A SNV Pathogenic 915368 GRCh37: 13:101890105-101890105
GRCh38: 13:101237754-101237754
5 NALCN NM_052867.4(NALCN):c.2563C>T (p.Arg855Ter) SNV Pathogenic 489164 rs376152742 GRCh37: 13:101759854-101759854
GRCh38: 13:101107503-101107503
6 NALCN NM_052867.4(NALCN):c.537del (p.Ile178_Trp179insTer) Deletion Pathogenic 684711 rs1594759803 GRCh37: 13:102029158-102029158
GRCh38: 13:101376807-101376807
7 NALCN NM_052867.4(NALCN):c.2758del (p.Ile920fs) Deletion Pathogenic 684710 rs1594211334 GRCh37: 13:101756777-101756777
GRCh38: 13:101104426-101104426
8 NALCN NM_052867.4(NALCN):c.321G>A (p.Trp107Ter) SNV Pathogenic 684709 rs1594761911 GRCh37: 13:102030975-102030975
GRCh38: 13:101378624-101378624
9 NALCN NM_052867.4(NALCN):c.4150C>T (p.Arg1384Ter) SNV Pathogenic 684708 rs1031314447 GRCh37: 13:101725983-101725983
GRCh38: 13:101073631-101073631
10 NALCN NM_052867.4(NALCN):c.2889+3_2889+6del Deletion Pathogenic 684707 rs1594211051 GRCh37: 13:101756640-101756643
GRCh38: 13:101104289-101104292
11 NALCN NM_052867.4(NALCN):c.4333A>T (p.Ile1445Leu) SNV Pathogenic 684706 rs1459166839 GRCh37: 13:101720383-101720383
GRCh38: 13:101068031-101068031
12 NALCN NM_052867.4(NALCN):c.2435dup (p.Glu813fs) Duplication Pathogenic 684705 rs1594218864 GRCh37: 13:101760069-101760070
GRCh38: 13:101107718-101107719
13 NALCN NM_052867.4(NALCN):c.3556C>T (p.Gln1186Ter) SNV Pathogenic 684704 rs1594168638 GRCh37: 13:101736089-101736089
GRCh38: 13:101083738-101083738
14 NALCN NM_052867.4(NALCN):c.4103+2T>C SNV Pathogenic 684703 rs1594146891 GRCh37: 13:101726863-101726863
GRCh38: 13:101074512-101074512
15 NALCN NM_052867.4(NALCN):c.4281C>A (p.Phe1427Leu) SNV Pathogenic 684702 rs1594134160 GRCh37: 13:101721096-101721096
GRCh38: 13:101068744-101068744
16 NALCN NM_052867.4(NALCN):c.3056dup (p.Leu1019fs) Duplication Pathogenic 684701 rs772394714 GRCh37: 13:101755523-101755524
GRCh38: 13:101103172-101103173
17 NALCN NM_052867.4(NALCN):c.2629del (p.Gln877fs) Deletion Pathogenic 684700 rs1594212468 GRCh37: 13:101757252-101757252
GRCh38: 13:101104901-101104901
18 NALCN NM_052867.4(NALCN):c.3022C>T (p.Arg1008Ter) SNV Pathogenic 684699 rs766421214 GRCh37: 13:101755558-101755558
GRCh38: 13:101103207-101103207
19 NALCN NM_052867.4(NALCN):c.3860G>T (p.Trp1287Leu) SNV Pathogenic 88687 rs587777068 GRCh37: 13:101733903-101733903
GRCh38: 13:101081552-101081552
20 NALCN NM_052867.4(NALCN):c.1489del (p.Tyr497fs) Deletion Pathogenic 88686 rs869025188 GRCh37: 13:101881881-101881881
GRCh38: 13:101229530-101229530
21 NALCN NM_052867.4(NALCN):c.2579+5G>A SNV Likely pathogenic 870580 GRCh37: 13:101759833-101759833
GRCh38: 13:101107482-101107482
22 NALCN NM_052867.4(NALCN):c.638del (p.Lys213fs) Deletion Likely pathogenic 996877 GRCh37: 13:102029057-102029057
GRCh38: 13:101376706-101376706
23 NALCN NM_052867.4(NALCN):c.946G>A (p.Val316Met) SNV Likely pathogenic 1029047 GRCh37: 13:101944442-101944442
GRCh38: 13:101292091-101292091
24 NALCN NM_052867.4(NALCN):c.4755+1G>T SNV Likely pathogenic 522142 rs1158141270 GRCh37: 13:101714319-101714319
GRCh38: 13:101061967-101061967
25 NALCN NM_052867.4(NALCN):c.2831dup (p.Thr945fs) Duplication Likely pathogenic 800865 rs1594211244 GRCh37: 13:101756703-101756704
GRCh38: 13:101104352-101104353
26 NALCN NM_052867.4(NALCN):c.3533T>C (p.Leu1178Pro) SNV Likely pathogenic 800878 rs1594168705 GRCh37: 13:101736112-101736112
GRCh38: 13:101083761-101083761
27 NALCN NM_052867.4(NALCN):c.2671del (p.Val891fs) Deletion Likely pathogenic 813894 rs1594211911 GRCh37: 13:101756967-101756967
GRCh38: 13:101104616-101104616
28 NALCN NM_052867.4(NALCN):c.883C>T (p.Arg295Cys) SNV Uncertain significance 784273 rs372035044 GRCh37: 13:101944634-101944634
GRCh38: 13:101292283-101292283
29 NALCN NM_052867.4(NALCN):c.410C>T (p.Ser137Leu) SNV Uncertain significance 523003 rs1555343688 GRCh37: 13:102029373-102029373
GRCh38: 13:101377022-101377022
30 NALCN-AS1 , NALCN NM_052867.4(NALCN):c.4978G>A (p.Ala1660Thr) SNV Uncertain significance 1033020 GRCh37: 13:101710336-101710336
GRCh38: 13:101057984-101057984
31 NALCN NM_052867.4(NALCN):c.2648G>T (p.Gly883Val) SNV Uncertain significance 915411 GRCh37: 13:101756990-101756990
GRCh38: 13:101104639-101104639
32 NALCN NM_052867.4(NALCN):c.2551C>G (p.Arg851Gly) SNV Uncertain significance 930541 GRCh37: 13:101759866-101759866
GRCh38: 13:101107515-101107515
33 NALCN NM_052867.4(NALCN):c.1100A>T (p.Asn367Ile) SNV Uncertain significance 931577 GRCh37: 13:101936318-101936318
GRCh38: 13:101283967-101283967
34 NALCN NM_052867.4(NALCN):c.2887C>G (p.Leu963Val) SNV not provided 972997 GRCh37: 13:101756648-101756648
GRCh38: 13:101104297-101104297

UniProtKB/Swiss-Prot genetic disease variations for Hypotonia, Infantile, with Psychomotor Retardation and Characteristic Facies 1:

72
# Symbol AA change Variation ID SNP ID
1 NALCN p.Trp1287Leu VAR_070599 rs587777068

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

Search GEO for disease gene expression data for Hypotonia, Infantile, with Psychomotor Retardation and Characteristic Facies 1.

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
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35 IUPHAR
36 KEGG
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39 LOVD
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44 MeSH
45 MESH via Orphanet
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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
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