HPE12
MCID: HLP031
MIFTS: 24

Holoprosencephaly 12 with or Without Pancreatic Agenesis (HPE12)

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

Aliases & Classifications for Holoprosencephaly 12 with or Without Pancreatic Agenesis

MalaCards integrated aliases for Holoprosencephaly 12 with or Without Pancreatic Agenesis:

Name: Holoprosencephaly 12 with or Without Pancreatic Agenesis 57 73 29 6
Hpe12 57 73
Holoprosencephaly 12, with or Without Pancreatic Agenesis 57
Pancreatic Agenesis-Holoprosencephaly Syndrome 58

Characteristics:

OMIM®:

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

Miscellaneous:
variable phenotype
de novo mutation
onset in utero
early death may occur


HPO:

31
holoprosencephaly 12 with or without pancreatic agenesis:
Inheritance autosomal dominant inheritance
Onset and clinical course congenital onset


Classifications:

Orphanet: 58  
Rare neurological diseases
Developmental anomalies during embryogenesis


Summaries for Holoprosencephaly 12 with or Without Pancreatic Agenesis

OMIM® : 57 Holoprosencephaly-12 with or without pancreatic agenesis (HPE12) is a developmental disorder characterized by abnormal separation of the embryonic forebrain (HPE) resulting in dysmorphic facial features and often, but not always, impaired neurologic development. Most patients with this form of HPE also have congenital absence of the pancreas, resulting in early-onset type 1 diabetes mellitus and requiring pancreatic enzyme replacement. Other features may include hearing loss and absence of the gallbladder (summary by De Franco et al., 2019 and Kruszka et al., 2019). For a phenotypic description and a discussion of genetic heterogeneity of holoprosencephaly, see HPE1 (236100). (618500) (Updated 05-Mar-2021)

MalaCards based summary : Holoprosencephaly 12 with or Without Pancreatic Agenesis, is also known as hpe12. An important gene associated with Holoprosencephaly 12 with or Without Pancreatic Agenesis is CNOT1 (CCR4-NOT Transcription Complex Subunit 1). Affiliated tissues include pancreas, bone and brain, and related phenotypes are agenesis of corpus callosum and intrauterine growth retardation

UniProtKB/Swiss-Prot : 73 Holoprosencephaly 12 with or without pancreatic agenesis: An autosomal dominant form of holoprosencephaly, a structural anomaly of the brain in which the developing forebrain fails to correctly separate into right and left hemispheres. Holoprosencephaly is genetically heterogeneous and associated with several distinct facies and phenotypic variability. HPE12 clinical features include abnormal forebrain development, dysmorphic features, global developmental delay, learning difficulties, and congenital absence of the pancreas in most patients, resulting in early-onset insulin-dependent diabetes mellitus. Other features may include hearing loss and absence of the gallbladder.

Related Diseases for Holoprosencephaly 12 with or Without Pancreatic Agenesis

Symptoms & Phenotypes for Holoprosencephaly 12 with or Without Pancreatic Agenesis

Human phenotypes related to Holoprosencephaly 12 with or Without Pancreatic Agenesis:

58 31 (show all 37)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 agenesis of corpus callosum 58 31 frequent (33%) Frequent (79-30%) HP:0001274
2 intrauterine growth retardation 58 31 frequent (33%) Frequent (79-30%) HP:0001511
3 small for gestational age 58 31 frequent (33%) Frequent (79-30%) HP:0001518
4 absent gallbladder 58 31 frequent (33%) Frequent (79-30%) HP:0011467
5 neonatal insulin-dependent diabetes mellitus 58 31 frequent (33%) Frequent (79-30%) HP:0000857
6 pancreatic aplasia 58 31 frequent (33%) Frequent (79-30%) HP:0100801
7 reduced c-peptide level 58 31 frequent (33%) Frequent (79-30%) HP:0030795
8 hypoamylasemia 58 31 frequent (33%) Frequent (79-30%) HP:0410289
9 decreased circulating lipoprotein lipase concentration 31 frequent (33%) HP:0031209
10 high palate 58 31 occasional (7.5%) Occasional (29-5%) HP:0000218
11 prominent occiput 58 31 occasional (7.5%) Occasional (29-5%) HP:0000269
12 low-set ears 58 31 occasional (7.5%) Occasional (29-5%) HP:0000369
13 hypoplasia of the zygomatic bone 58 31 occasional (7.5%) Occasional (29-5%) HP:0010669
14 hypotelorism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000601
15 single median maxillary incisor 58 31 occasional (7.5%) Occasional (29-5%) HP:0006315
16 sloping forehead 58 31 occasional (7.5%) Occasional (29-5%) HP:0000340
17 hypoxemia 58 31 occasional (7.5%) Occasional (29-5%) HP:0012418
18 abnormality of the pinna 58 31 occasional (7.5%) Occasional (29-5%) HP:0000377
19 semilobar holoprosencephaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0002507
20 aplasia/hypoplasia of the phalanges of the thumb 58 31 occasional (7.5%) Occasional (29-5%) HP:0009658
21 abnormality of the external nose 58 31 occasional (7.5%) Occasional (29-5%) HP:0010938
22 spasticity 31 very rare (1%) HP:0001257
23 diabetes insipidus 31 very rare (1%) HP:0000873
24 seizure 31 very rare (1%) HP:0001250
25 global developmental delay 31 HP:0001263
26 depressed nasal bridge 31 HP:0005280
27 microtia 31 HP:0008551
28 microcephaly 31 HP:0000252
29 sensorineural hearing impairment 31 HP:0000407
30 type i diabetes mellitus 31 HP:0100651
31 epicanthus 31 HP:0000286
32 conductive hearing impairment 31 HP:0000405
33 holoprosencephaly 58 Frequent (79-30%)
34 long philtrum 31 HP:0000343
35 generalized hypotonia 31 HP:0001290
36 abnormality of brain morphology 58 Frequent (79-30%)
37 decreased lipoprotein lipase activity 58 Frequent (79-30%)

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Head And Neck Nose:
depressed nasal bridge

Head And Neck Head:
microcephaly

Head And Neck Face:
long philtrum
dysmorphic features, variable
receding forehead
hypoplastic zygomatic bone

Head And Neck Mouth:
high-arched palate

Endocrine Features:
insulin-dependent diabetes mellitus
diabetes insipidus (1 patient)

Muscle Soft Tissue:
low muscle tone

Abdomen Biliary Tract:
gall bladder agenesis

Head And Neck Ears:
microtia
low-set ears
dysplastic ears
hearing loss, conductive
hearing loss, sensorineural

Growth Other:
intrauterine growth retardation

Head And Neck Eyes:
hypotelorism
epicanthal folds

Neurologic Central Nervous System:
seizures (in some patients)
learning difficulties
corpus callosum abnormalities
spasticity (1 patient)
global developmental delay (in most patients)
more
Abdomen Pancreas:
pancreatic exocrine deficiency
pancreatic agenesis
pancreatic endocrine deficiency

Head And Neck Teeth:
large central incisors

Clinical features from OMIM®:

618500 (Updated 05-Mar-2021)

Drugs & Therapeutics for Holoprosencephaly 12 with or Without Pancreatic Agenesis

Search Clinical Trials , NIH Clinical Center for Holoprosencephaly 12 with or Without Pancreatic Agenesis

Genetic Tests for Holoprosencephaly 12 with or Without Pancreatic Agenesis

Genetic tests related to Holoprosencephaly 12 with or Without Pancreatic Agenesis:

# Genetic test Affiliating Genes
1 Holoprosencephaly 12 with or Without Pancreatic Agenesis 29 CNOT1

Anatomical Context for Holoprosencephaly 12 with or Without Pancreatic Agenesis

MalaCards organs/tissues related to Holoprosencephaly 12 with or Without Pancreatic Agenesis:

40
Pancreas, Bone, Brain

Publications for Holoprosencephaly 12 with or Without Pancreatic Agenesis

Articles related to Holoprosencephaly 12 with or Without Pancreatic Agenesis:

# Title Authors PMID Year
1
A Specific CNOT1 Mutation Results in a Novel Syndrome of Pancreatic Agenesis and Holoprosencephaly through Impaired Pancreatic and Neurological Development. 6 57
31006513 2019
2
A CCR4-NOT Transcription Complex, Subunit 1, CNOT1, Variant Associated with Holoprosencephaly. 57 6
31006510 2019
3
Pancreas and gallbladder agenesis in a newborn with semilobar holoprosencephaly, a case report. 6 57
28525974 2017
4
De Novo Variants in CNOT1, a Central Component of the CCR4-NOT Complex Involved in Gene Expression and RNA and Protein Stability, Cause Neurodevelopmental Delay. 6
32553196 2020

Variations for Holoprosencephaly 12 with or Without Pancreatic Agenesis

ClinVar genetic disease variations for Holoprosencephaly 12 with or Without Pancreatic Agenesis:

6
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 CNOT1 NM_016284.5(CNOT1):c.1603C>T (p.Arg535Cys) SNV Pathogenic 619606 rs1567417422 16:58610468-58610468 16:58576564-58576564

UniProtKB/Swiss-Prot genetic disease variations for Holoprosencephaly 12 with or Without Pancreatic Agenesis:

73
# Symbol AA change Variation ID SNP ID
1 CNOT1 p.Arg535Cys VAR_083066 rs156741742

Expression for Holoprosencephaly 12 with or Without Pancreatic Agenesis

Search GEO for disease gene expression data for Holoprosencephaly 12 with or Without Pancreatic Agenesis.

Pathways for Holoprosencephaly 12 with or Without Pancreatic Agenesis

GO Terms for Holoprosencephaly 12 with or Without Pancreatic Agenesis

Sources for Holoprosencephaly 12 with or Without Pancreatic Agenesis

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 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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