IMNEPD
MCID: NRL023
MIFTS: 32

Neurologic, Endocrine, and Pancreatic Disease, Multisystem, Infantile-Onset (IMNEPD)

Categories: Ear diseases, Endocrine diseases, Fetal diseases, Gastrointestinal diseases, Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Neurologic, Endocrine, and Pancreatic Disease, Multisystem,...

MalaCards integrated aliases for Neurologic, Endocrine, and Pancreatic Disease, Multisystem, Infantile-Onset:

Name: Neurologic, Endocrine, and Pancreatic Disease, Multisystem, Infantile-Onset 57 72 29 6 70
Imnepd 57 58 72
Infantile-Onset Multisystem Neurologic, Endocrine, and Pancreatic Disease 57 36
Multisystem Neurologic, Endocrine, and Pancreatic Disease, Infantile-Onset 39
Infantile Multisystem Neurologic-Endocrine-Pancreatic Disease 58

Characteristics:

Orphanet epidemiological data:

58
infantile multisystem neurologic-endocrine-pancreatic disease
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy;

OMIM®:

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

Miscellaneous:
progressive disorder
onset at birth
some patients may become wheelchair-bound
highly variable expressivity


HPO:

31
neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset:
Inheritance autosomal recessive inheritance
Onset and clinical course progressive congenital onset


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare gastroenterological diseases
Rare otorhinolaryngological diseases
Rare endocrine diseases
Developmental anomalies during embryogenesis


Summaries for Neurologic, Endocrine, and Pancreatic Disease, Multisystem,...

OMIM® : 57 Infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD) is an autosomal recessive multisystemic disorder with variable expressivity. The core features usually include global developmental delay with impaired intellectual development and speech delay, ataxia, sensorineural hearing loss, and pancreatic insufficiency. Additional features may include peripheral neuropathy, postnatal microcephaly, dysmorphic facial features, and cerebellar atrophy. However, some patients may not display all features (summary by Picker-Minh et al., 2016, Sharkia et al., 2017). (616263) (Updated 20-May-2021)

MalaCards based summary : Neurologic, Endocrine, and Pancreatic Disease, Multisystem, Infantile-Onset, also known as imnepd, is related to ataxia and polyneuropathy, adult-onset and alacrima, achalasia, and mental retardation syndrome, and has symptoms including ataxia An important gene associated with Neurologic, Endocrine, and Pancreatic Disease, Multisystem, Infantile-Onset is PTRH2 (Peptidyl-TRNA Hydrolase 2). Affiliated tissues include pancreas, skeletal muscle and liver, and related phenotypes are global developmental delay and abnormal facial shape

KEGG : 36 Infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD) is a novel intellectual disability phenotype caused by homozygous mutations in PTRH2. IMNEPD is characterized by intellectual disability, microcephaly, progressive ataxia, sensorineural deafness, peripheral neuropathy, exocrine pancreas insufficiency, and hypothyroidism. PTRH2 encodes a primarily mitochondrial protein involved in integrin-mediated cell survival and apoptosis signaling.

UniProtKB/Swiss-Prot : 72 Neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset: A progressive multisystem disease characterized by a variety of neurologic, endocrine, and, in some patients, pancreatic features. Variable clinical symptoms include global developmental delay, hypotonia, hearing loss, ataxia, hyporeflexia, facial dysmorphism, hypothyroidism, and pancreatic insufficiency.

Related Diseases for Neurologic, Endocrine, and Pancreatic Disease, Multisystem,...

Diseases related to Neurologic, Endocrine, and Pancreatic Disease, Multisystem, Infantile-Onset via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 13)
# Related Disease Score Top Affiliating Genes
1 ataxia and polyneuropathy, adult-onset 10.0
2 alacrima, achalasia, and mental retardation syndrome 10.0
3 microcephaly 10.0
4 peripheral nervous system disease 10.0
5 neuropathy 10.0
6 branchiootic syndrome 1 9.9
7 diabetes mellitus, ketosis-prone 9.9
8 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 9.9
9 autosomal recessive disease 9.9
10 metabolic acidosis 9.9
11 sensorineural hearing loss 9.9
12 polyneuropathy 9.9
13 diabetes mellitus 9.9

Graphical network of the top 20 diseases related to Neurologic, Endocrine, and Pancreatic Disease, Multisystem, Infantile-Onset:



Diseases related to Neurologic, Endocrine, and Pancreatic Disease, Multisystem, Infantile-Onset

Symptoms & Phenotypes for Neurologic, Endocrine, and Pancreatic Disease, Multisystem,...

Human phenotypes related to Neurologic, Endocrine, and Pancreatic Disease, Multisystem, Infantile-Onset:

58 31 (show top 50) (show all 64)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 global developmental delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0001263
2 abnormal facial shape 58 31 hallmark (90%) Very frequent (99-80%) HP:0001999
3 sensorineural hearing impairment 58 31 hallmark (90%) Very frequent (99-80%) HP:0000407
4 exocrine pancreatic insufficiency 58 31 hallmark (90%) Very frequent (99-80%) HP:0001738
5 motor delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0001270
6 intellectual disability, moderate 58 31 hallmark (90%) Very frequent (99-80%) HP:0002342
7 distal amyotrophy 58 31 hallmark (90%) Very frequent (99-80%) HP:0003693
8 failure to thrive 58 31 frequent (33%) Frequent (79-30%) HP:0001508
9 eeg abnormality 58 31 frequent (33%) Frequent (79-30%) HP:0002353
10 facial palsy 58 31 frequent (33%) Frequent (79-30%) HP:0010628
11 diabetes mellitus 58 31 very rare (1%) Frequent (79-30%) HP:0000819
12 neonatal hypotonia 58 31 frequent (33%) Frequent (79-30%) HP:0001319
13 brachycephaly 58 31 frequent (33%) Frequent (79-30%) HP:0000248
14 achilles tendon contracture 58 31 frequent (33%) Frequent (79-30%) HP:0001771
15 thin upper lip vermilion 58 31 frequent (33%) Frequent (79-30%) HP:0000219
16 dysmetria 58 31 frequent (33%) Frequent (79-30%) HP:0001310
17 proximal placement of thumb 58 31 frequent (33%) Frequent (79-30%) HP:0009623
18 postnatal microcephaly 58 31 frequent (33%) Frequent (79-30%) HP:0005484
19 distal muscle weakness 58 31 frequent (33%) Frequent (79-30%) HP:0002460
20 long fingers 58 31 frequent (33%) Frequent (79-30%) HP:0100807
21 exotropia 58 31 frequent (33%) Frequent (79-30%) HP:0000577
22 abnormality of the midface 58 31 frequent (33%) Frequent (79-30%) HP:0000309
23 mild postnatal growth retardation 58 31 frequent (33%) Frequent (79-30%) HP:0001530
24 cerebellar hemisphere hypoplasia 58 31 frequent (33%) Frequent (79-30%) HP:0100307
25 hypothyroidism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000821
26 hepatomegaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0002240
27 hypertelorism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000316
28 delayed puberty 58 31 very rare (1%) Occasional (29-5%) HP:0000823
29 congenital hip dislocation 58 31 occasional (7.5%) Occasional (29-5%) HP:0001374
30 decreased fetal movement 58 31 occasional (7.5%) Occasional (29-5%) HP:0001558
31 decreased motor nerve conduction velocity 58 31 occasional (7.5%) Occasional (29-5%) HP:0003431
32 shawl scrotum 58 31 occasional (7.5%) Occasional (29-5%) HP:0000049
33 hypoxemia 58 31 occasional (7.5%) Occasional (29-5%) HP:0012418
34 talipes equinovalgus 58 31 occasional (7.5%) Occasional (29-5%) HP:0001772
35 aplasia/hypoplasia of the pancreas 58 31 occasional (7.5%) Occasional (29-5%) HP:0100800
36 abnormal liver parenchyma morphology 58 31 occasional (7.5%) Occasional (29-5%) HP:0030146
37 joint contracture of the hand 58 31 occasional (7.5%) Occasional (29-5%) HP:0009473
38 decreased sensory nerve conduction velocity 58 31 occasional (7.5%) Occasional (29-5%) HP:0003448
39 skeletal muscle fibrosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0030951
40 abnormality of the hallux 58 31 occasional (7.5%) Occasional (29-5%) HP:0001844
41 ulnar deviation of the 2nd finger 58 31 occasional (7.5%) Occasional (29-5%) HP:0009464
42 hyperechogenic pancreas 58 31 occasional (7.5%) Occasional (29-5%) HP:0006276
43 ulnar deviation of the 3rd finger 58 31 occasional (7.5%) Occasional (29-5%) HP:0009463
44 generalized myoclonic seizure 31 occasional (7.5%) HP:0002123
45 seizure 31 very rare (1%) HP:0001250
46 ataxia 58 31 Very frequent (99-80%) HP:0001251
47 intellectual disability 31 HP:0001249
48 short stature 31 HP:0004322
49 flexion contracture 31 HP:0001371
50 hepatic steatosis 31 HP:0001397

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Growth Other:
failure to thrive
poor postnatal growth

Head And Neck Eyes:
hypertelorism
exotropia

Head And Neck Head:
brachycephaly
microcephaly, postnatal, progressive

Skeletal Pelvis:
hip dislocation

Neurologic Peripheral Nervous System:
hyporeflexia
demyelinating sensorimotor peripheral neuropathy

Abdomen Pancreas:
pancreatic fibrosis
pancreatic exocrine insufficiency (in some patients)
pancreatic endocrine insufficiency, mild (in 1 patient)

Muscle Soft Tissue:
distal muscle weakness
hypotonia

Head And Neck Face:
midface hypoplasia

Skeletal Feet:
foot deformities
clubfoot

Endocrine Features:
hypothyroidism (in some patients)
delayed puberty (in some patients)
diabetes mellitus (in some patients)
pancreatic endocrine dysfunction (in some patients)

Abdomen Liver:
hepatomegaly
hepatic steatosis
hepatic fibrosis

Growth Height:
short stature

Head And Neck Mouth:
thin upper lip vermilion

Neurologic Central Nervous System:
dysmetria
seizures (rare)
intellectual disability (in some patients)
delayed psychomotor development (in some patients)
cerebellar atrophy, progressive (in some patients)
more
Abdomen Gastrointestinal:
steatorrhea

Genitourinary External Genitalia Male:
shawl scrotum

Head And Neck Ears:
sensorineural deafness

Skeletal:
joint contractures

Skeletal Hands:
proximally placed thumbs
finger deformities

Clinical features from OMIM®:

616263 (Updated 20-May-2021)

UMLS symptoms related to Neurologic, Endocrine, and Pancreatic Disease, Multisystem, Infantile-Onset:


ataxia

Drugs & Therapeutics for Neurologic, Endocrine, and Pancreatic Disease, Multisystem,...

Search Clinical Trials , NIH Clinical Center for Neurologic, Endocrine, and Pancreatic Disease, Multisystem, Infantile-Onset

Genetic Tests for Neurologic, Endocrine, and Pancreatic Disease, Multisystem,...

Genetic tests related to Neurologic, Endocrine, and Pancreatic Disease, Multisystem, Infantile-Onset:

# Genetic test Affiliating Genes
1 Neurologic, Endocrine, and Pancreatic Disease, Multisystem, Infantile-Onset 29 PTRH2

Anatomical Context for Neurologic, Endocrine, and Pancreatic Disease, Multisystem,...

MalaCards organs/tissues related to Neurologic, Endocrine, and Pancreatic Disease, Multisystem, Infantile-Onset:

40
Pancreas, Skeletal Muscle, Liver

Publications for Neurologic, Endocrine, and Pancreatic Disease, Multisystem,...

Articles related to Neurologic, Endocrine, and Pancreatic Disease, Multisystem, Infantile-Onset:

# Title Authors PMID Year
1
Diabetes mellitus in an adolescent girl with intellectual disability caused by novel single base pair duplication in the PTRH2 gene: Expanding the clinical spectrum of IMNEPD. 6 57 61
33092935 2021
2
Infantile-Onset Multisystem Neurologic, Endocrine, and Pancreatic Disease: Case and Review. 61 6 57
31057140 2019
3
Phenotype variability of infantile-onset multisystem neurologic, endocrine, and pancreatic disease IMNEPD. 61 57 6
27129381 2016
4
Mutations in PTRH2 cause novel infantile-onset multisystem disease with intellectual disability, microcephaly, progressive ataxia, and muscle weakness. 6 61 57
25574476 2014
5
Homozygous mutation in PTRH2 gene causes progressive sensorineural deafness and peripheral neuropathy. 6 57
28328138 2017
6
Accelerating novel candidate gene discovery in neurogenetic disorders via whole-exome sequencing of prescreened multiplex consanguineous families. 57 6
25558065 2015
7
Anoikis effector Bit1 negatively regulates Erk activity. 57
18218778 2008
8
A Novel Synergistic Association of Variants in PTRH2 and KIF1A Relates to a Syndrome of Hereditary Axonopathy, Outer Hair Cell Dysfunction, Intellectual Disability, Pancreatic Lipomatosis, Diabetes, Cerebellar Atrophy, and Vertebral Artery Hypoplasia. 61
33717719 2021
9
PTRH2: an adhesion regulated molecular switch at the nexus of life, death, and differentiation. 61
33298880 2020

Variations for Neurologic, Endocrine, and Pancreatic Disease, Multisystem,...

ClinVar genetic disease variations for Neurologic, Endocrine, and Pancreatic Disease, Multisystem, Infantile-Onset:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 PTRH2 NM_001015509.2(PTRH2):c.272_273del (p.Ala91fs) Deletion Pathogenic 183428 rs786201017 GRCh37: 17:57775070-57775071
GRCh38: 17:59697709-59697710
2 PTRH2 NM_016077.5(PTRH2):c.324G>A (p.Trp108Ter) SNV Pathogenic 695110 rs1268684924 GRCh37: 17:57775016-57775016
GRCh38: 17:59697655-59697655
3 PTRH2 NM_016077.5(PTRH2):c.127dup (p.Ser43fs) Duplication Pathogenic 1048079 GRCh37: 17:57775212-57775213
GRCh38: 17:59697851-59697852
4 PTRH2 NM_016077.4(PTRH2):c.254A>C (p.Gln85Pro) SNV Pathogenic 183332 rs730882234 GRCh37: 17:57775086-57775086
GRCh38: 17:59697725-59697725
5 PTRH2 NM_016077.5(PTRH2):c.68T>C (p.Val23Ala) SNV Likely pathogenic 996539 GRCh37: 17:57775272-57775272
GRCh38: 17:59697911-59697911

UniProtKB/Swiss-Prot genetic disease variations for Neurologic, Endocrine, and Pancreatic Disease, Multisystem, Infantile-Onset:

72
# Symbol AA change Variation ID SNP ID
1 PTRH2 p.Gln85Pro VAR_073386 rs730882234

Expression for Neurologic, Endocrine, and Pancreatic Disease, Multisystem,...

Search GEO for disease gene expression data for Neurologic, Endocrine, and Pancreatic Disease, Multisystem, Infantile-Onset.

Pathways for Neurologic, Endocrine, and Pancreatic Disease, Multisystem,...

GO Terms for Neurologic, Endocrine, and Pancreatic Disease, Multisystem,...

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