PCH3
MCID: PNT037
MIFTS: 42

Pontocerebellar Hypoplasia, Type 3 (PCH3)

Categories: Eye diseases, Fetal diseases, Genetic diseases, Mental diseases, Metabolic diseases, Muscle diseases, Neuronal diseases, Rare diseases, Respiratory diseases

Aliases & Classifications for Pontocerebellar Hypoplasia, Type 3

MalaCards integrated aliases for Pontocerebellar Hypoplasia, Type 3:

Name: Pontocerebellar Hypoplasia, Type 3 57 13
Pontocerebellar Hypoplasia Type 3 12 20 58 29 6 44 15 70
Cerebellar Atrophy with Progressive Microcephaly 57 20 58 72
Pch with Optic Atrophy 57 20 72
Pch3 57 58 72
Clam 57 20 72
Cerebellar Atrophy with Progressive Microcephaly; Clam 57
Hypoplasia, Pontocerebellar, Type 3 39
Pontocerebellar Hypoplasia 3 72

Characteristics:

Orphanet epidemiological data:

58
pontocerebellar hypoplasia type 3
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM®:

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

Miscellaneous:
progressive disorder
onset at birth
one consanguineous family has been found to carry a homozygous mutation in the pclo gene (last curated june 2015)


HPO:

31
pontocerebellar hypoplasia, type 3:
Inheritance autosomal recessive inheritance
Onset and clinical course progressive congenital onset


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare eye diseases
Developmental anomalies during embryogenesis


External Ids:

Disease Ontology 12 DOID:0060272
OMIM® 57 608027
OMIM Phenotypic Series 57 PS607596
SNOMED-CT 67 718609003
MESH via Orphanet 45 C548072
ICD10 via Orphanet 33 Q04.3
UMLS via Orphanet 71 C1842687
Orphanet 58 ORPHA97249
MedGen 41 C1842687
UMLS 70 C1842687

Summaries for Pontocerebellar Hypoplasia, Type 3

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 97249 Definition Pontocerebellar hypoplasia type 3 (PCH3), also known as cerebellar atrophy with progressive microcephaly (CLAM) is a rare form of pontocerebellar hypoplasia (see this term) with autosomal recessive transmission characterized neonatally by hypotonia and impaired swallowing and from infancy onward by seizures, optic atrophy and short stature, but none of the clinical findings are specific for PCH3. Epidemiology To date, PCH3 is reported in only 3 families. Clinical description Neonatally, PCH3 is characterized by hypotonia and impaired swallowing. From infancy onwards, the main features of PCH3 include progressive microcephaly with brachycephaly, optic atrophy, seizures during the first year of life, severe developmental delay, truncal hypotonia, with increased limb deep tendon reflexes and signs of spasticity of the limbs. Other characteristics such as facial dysmorphism (low set ears and prominent eyes), short stature and low weight are also reported. None of the clinical findings are specific. Etiology The etiology of PCH3 remains largely elusive. In 2 families, an implication of locus 7q11-21 has been demonstrated. PCH3 is inherited in an autosomal recessive manner. Diagnostic methods MRI demonstrates neocortical and pontocerebellar hypoplasia with pons and cerebellum equally affected a small brainstem, prominent sulci and lateral ventricles and decreased cerebral white matter volume. It is recommended to limit the diagnosis of PCH3 to families with PCH and linkage to 7q11-21, until more precise identification of the associated gene becomes possible. Prognosis There is no information on life expectancy, but reported PCH3 patients do not appear to regress.

MalaCards based summary : Pontocerebellar Hypoplasia, Type 3, also known as pontocerebellar hypoplasia type 3, is related to pontocerebellar hypoplasia and microcephaly, and has symptoms including seizures and muscle spasticity. An important gene associated with Pontocerebellar Hypoplasia, Type 3 is PCLO (Piccolo Presynaptic Cytomatrix Protein). The drugs Decitabine and Azacitidine have been mentioned in the context of this disorder. Affiliated tissues include cerebellum, pons and eye, and related phenotypes are spasticity and hyperreflexia

Disease Ontology : 12 A pontocerebellar hypoplasia that is characterized by progressive microcephaly, hypotonia, dysmorphic features, profound intellectual disability and seizure, has material basis in autosomal recessive inheritance of mutation in the PCLO gene.

OMIM® : 57 Pontocerebellar hypoplasia (PCH) refers to a heterogeneous group of disorders characterized by an abnormally small cerebellum and brainstem. Clinical features vary, but usually include severe developmental delay, dysmorphic features, seizures, and early death (summary by Durmaz et al., 2009). For a phenotypic description and a discussion of genetic heterogeneity of PCH, see PCH1 (607596). (608027) (Updated 05-Apr-2021)

UniProtKB/Swiss-Prot : 72 Pontocerebellar hypoplasia 3: A form of pontocerebellar hypoplasia, a disorder characterized by structural defects of the pons and cerebellum. Brain MRI shows an abnormally small cerebellum and brainstem, decreased cerebral white matter, and a thin corpus callosum. PCH3 features include seizures, short stature, optic atrophy, progressive microcephaly, severe developmental delay.

Related Diseases for Pontocerebellar Hypoplasia, Type 3

Graphical network of the top 20 diseases related to Pontocerebellar Hypoplasia, Type 3:



Diseases related to Pontocerebellar Hypoplasia, Type 3

Symptoms & Phenotypes for Pontocerebellar Hypoplasia, Type 3

Human phenotypes related to Pontocerebellar Hypoplasia, Type 3:

31 (show all 28)
# Description HPO Frequency HPO Source Accession
1 spasticity 31 HP:0001257
2 hyperreflexia 31 HP:0001347
3 hearing impairment 31 HP:0000365
4 global developmental delay 31 HP:0001263
5 depressed nasal bridge 31 HP:0005280
6 macrotia 31 HP:0000400
7 optic atrophy 31 HP:0000648
8 neonatal hypotonia 31 HP:0001319
9 short stature 31 HP:0004322
10 brachycephaly 31 HP:0000248
11 full cheeks 31 HP:0000293
12 low-set ears 31 HP:0000369
13 high, narrow palate 31 HP:0002705
14 downturned corners of mouth 31 HP:0002714
15 long philtrum 31 HP:0000343
16 proptosis 31 HP:0000520
17 decreased body weight 31 HP:0004325
18 cerebellar hypoplasia 31 HP:0001321
19 hypoplasia of the corpus callosum 31 HP:0002079
20 poor head control 31 HP:0002421
21 cerebellar atrophy 31 HP:0001272
22 cerebral atrophy 31 HP:0002059
23 muscular hypotonia of the trunk 31 HP:0008936
24 long palpebral fissure 31 HP:0000637
25 hypoplasia of the pons 31 HP:0012110
26 hypoplasia of the brainstem 31 HP:0002365
27 progressive microcephaly 31 HP:0000253
28 seizure 31 HP:0001250

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
seizures
spasticity
hyperreflexia
neonatal hypotonia
hypoplasia of the corpus callosum
more
Head And Neck Nose:
depressed nasal bridge

Head And Neck Eyes:
optic atrophy
prominent eyes
wide palpebral fissures

Head And Neck Face:
full cheeks
long philtrum

Head And Neck Mouth:
high arched palate
downturned corners of the mouth

Head And Neck Ears:
hearing impairment
low-set ears
large ears

Head And Neck Head:
microcephaly
brachycephaly

Growth Height:
short stature

Growth Weight:
low weight

Clinical features from OMIM®:

608027 (Updated 05-Apr-2021)

UMLS symptoms related to Pontocerebellar Hypoplasia, Type 3:


seizures; muscle spasticity

Drugs & Therapeutics for Pontocerebellar Hypoplasia, Type 3

Drugs for Pontocerebellar Hypoplasia, Type 3 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 23)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Decitabine Approved, Investigational Phase 1, Phase 2 2353-33-5 451668
2
Azacitidine Approved, Investigational Phase 1, Phase 2 320-67-2 9444
3
Clofarabine Approved, Investigational Phase 2 123318-82-1 119182
4
Cytarabine Approved, Investigational Phase 1, Phase 2 147-94-4 6253
5
Sorafenib Approved, Investigational Phase 1, Phase 2 284461-73-0 216239 406563
6
Cladribine Approved, Investigational Phase 1, Phase 2 4291-63-8 20279
7
Sargramostim Approved, Investigational Phase 1, Phase 2 123774-72-1, 83869-56-1
8
Lenograstim Approved, Investigational Phase 1, Phase 2 135968-09-1
9
Mitoxantrone Approved, Investigational Phase 1, Phase 2 65271-80-9 4212
10 Cordycepin Investigational Phase 1, Phase 2 73-03-0
11
Molgramostim Investigational Phase 1, Phase 2 99283-10-0
12 2-chloro-3'-deoxyadenosine Phase 1, Phase 2
13 Immunologic Factors Phase 1, Phase 2
14 Adjuvants, Immunologic Phase 1, Phase 2
15 Immunosuppressive Agents Phase 1, Phase 2
16 Analgesics Phase 1, Phase 2
17 Antiviral Agents Phase 1, Phase 2
18 Antimetabolites Phase 1, Phase 2
19 Protein Kinase Inhibitors Phase 1, Phase 2
20 Anti-Infective Agents Phase 1, Phase 2
21
tannic acid Approved 1401-55-4
22
Benzocaine Approved, Investigational 1994-09-7, 94-09-7 2337
23 Pharmaceutical Solutions

Interventional clinical trials:

(show all 13)
# Name Status NCT ID Phase Drugs
1 Does Prescriptive Treatment of the Hips Improve Outcomes in Patients With Low Back Pain? A Randomized Controlled Trial Completed NCT01900925 Phase 2, Phase 3
2 Phase 1/2 Study of Concurrent Decitabine in Combination With G-CSF, Cladribine, Cytarabine, and Mitoxantrone (G-CLAM) in Adults With Newly Diagnosed Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndromes (MDS) Completed NCT02921061 Phase 1, Phase 2 Cladribine;Cytarabine;Decitabine;Mitoxantrone Hydrochloride
3 A Phase 1/2 Trial of G-CSF, Cladribine, Cytarabine, and Dose-Escalated Mitoxantrone (G-CLAM) in Adults With Newly Diagnosed or Relapsed/Refractory Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndromes (MDS) Completed NCT02044796 Phase 1, Phase 2 Cladribine;Cytarabine;Mitoxantrone Hydrochloride
4 Clofarabine, Cytarabine and Mitoxantrone (CLAM) for Relapsed or Refractory AML Completed NCT02686593 Phase 2 Clofarabine, AraC, mitoxantrone (CLAM)
5 Addition of Sorafenib to G-CSF, Cladribine, Cytarabine, and Mitoxantrone (G-CLAM) in Adults With Newly-Diagnosed Acute Myeloid Leukemia (AML) Independent of FLT3-ITD Status: A Phase 1/2 Study Recruiting NCT02728050 Phase 1, Phase 2 Cladribine;Cytarabine;Mitoxantrone;Sorafenib
6 Dose-Finding (Phase 1) Study of Continuous Infusion Cladribine, Cytarabine and Mitoxantrone (CI-CLAM) for Adults With Relapsed/Refractory Acute Myeloid Leukemia or Other High-Grade Myeloid Neoplasms Treated at UW/SCCA Recruiting NCT04196010 Phase 1 Cladribine;Cytarabine;Mitoxantrone
7 Additional Gluteal Control Training for Low Back Pain With Functional Leg Length Inequality: A Ramdomized Controlled Trail Completed NCT03554746
8 Impact of Adding Transcutaneous Electrical Nerve Stimulation to Conventional Physical Therapy Exercise on Pain Relief Among Patients With Pudendal Neuralgia. Completed NCT04455659
9 Effect of Two Strengthening Protocols for Lower Limbs in Patients With Patellofemoral Pain: Randomized Clinical Trial Completed NCT03163290
10 Feasibility and Preliminary Effects of a Mobile App on Sleep Disturbance Completed NCT04045275
11 Acute Effect of a Gluteal Activation Warm-up on Hip Muscle Activity and Kinematics During a Single Leg Squat Completed NCT04301947
12 Randomized Control Trial of the Effectiveness of the Social Competence Promotion Program for Young Adolescents Aimed at Preventing Substance Use Among Students in Chile Recruiting NCT04236947
13 Department of Traditional Chinese Medicine, Keelung Chang Gung Memorial Hospital Active, not recruiting NCT04429737

Search NIH Clinical Center for Pontocerebellar Hypoplasia, Type 3

Cochrane evidence based reviews: pontocerebellar hypoplasia type 3

Genetic Tests for Pontocerebellar Hypoplasia, Type 3

Genetic tests related to Pontocerebellar Hypoplasia, Type 3:

# Genetic test Affiliating Genes
1 Pontocerebellar Hypoplasia Type 3 29 PCLO

Anatomical Context for Pontocerebellar Hypoplasia, Type 3

MalaCards organs/tissues related to Pontocerebellar Hypoplasia, Type 3:

40
Cerebellum, Pons, Eye, Brain, Myeloid

Publications for Pontocerebellar Hypoplasia, Type 3

Articles related to Pontocerebellar Hypoplasia, Type 3:

# Title Authors PMID Year
1
Loss of PCLO function underlies pontocerebellar hypoplasia type III. 57 6
25832664 2015
2
A novel form of pontocerebellar hypoplasia maps to chromosome 7q11-21. 57 6
12771259 2003
3
Pontocerebellar hypoplasia type III (CLAM): extended phenotype and novel molecular findings. 57
19277761 2009
4
Congenital pontocerebellar atrophy in three patients: clinical, radiologic and etiologic considerations. 57
8912329 1996
5
Loss of Piccolo Function in Rats Induces Cerebellar Network Dysfunction and Pontocerebellar Hypoplasia Type 3-like Phenotypes. 61
32122952 2020
6
Critical role for Piccolo in synaptic vesicle retrieval. 61
31074746 2019
7
Pontocerebellar Hypoplasia Maps to Chromosome 7q11.23: An Autopsy Case Report of a Novel Genetic Variant. 61
31885998 2019
8
A de novo CASK mutation in pontocerebellar hypoplasia type 3 with early myoclonic epilepsy and tetralogy of Fallot. 61
23623288 2014
9
Pontocerebellar hypoplasia type 3 with tetralogy of Fallot. 61
21880448 2012
10
Pontocerebellar hypoplasia type 3 with severe vitamin A deficiency. 61
21215917 2011

Variations for Pontocerebellar Hypoplasia, Type 3

ClinVar genetic disease variations for Pontocerebellar Hypoplasia, Type 3:

6 (show all 25)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 PCLO NM_033026.6(PCLO):c.10624C>T (p.Arg3542Ter) SNV Pathogenic 193026 rs746260871 GRCh37: 7:82579280-82579280
GRCh38: 7:82949964-82949964
2 PCLO NM_033026.6(PCLO):c.1030C>T (p.Gln344Ter) SNV Pathogenic 1031530 GRCh37: 7:82784927-82784927
GRCh38: 7:83155611-83155611
3 PCLO NM_033026.6(PCLO):c.2532dup (p.Gln845fs) Duplication Likely pathogenic 800508 rs1584071201 GRCh37: 7:82764333-82764334
GRCh38: 7:83135017-83135018
4 PCLO NM_033026.6(PCLO):c.10918T>C (p.Phe3640Leu) SNV Uncertain significance 1028487 GRCh37: 7:82578986-82578986
GRCh38: 7:82949670-82949670
5 PCLO NM_033026.6(PCLO):c.1110G>T (p.Lys370Asn) SNV Uncertain significance 1028488 GRCh37: 7:82784847-82784847
GRCh38: 7:83155531-83155531
6 PCLO NM_033026.6(PCLO):c.11578C>T (p.Pro3860Ser) SNV Uncertain significance 1028489 GRCh37: 7:82545724-82545724
GRCh38: 7:82916408-82916408
7 PCLO NM_033026.6(PCLO):c.1297G>A (p.Ala433Thr) SNV Uncertain significance 1013552 GRCh37: 7:82784660-82784660
GRCh38: 7:83155344-83155344
8 PCLO NM_033026.6(PCLO):c.13571C>T (p.Pro4524Leu) SNV Uncertain significance 1028490 GRCh37: 7:82508736-82508736
GRCh38: 7:82879420-82879420
9 PCLO NM_033026.6(PCLO):c.1585C>A (p.Pro529Thr) SNV Uncertain significance 1028491 GRCh37: 7:82784372-82784372
GRCh38: 7:83155056-83155056
10 PCLO NM_033026.6(PCLO):c.3367C>T (p.Arg1123Cys) SNV Uncertain significance 1028492 GRCh37: 7:82595737-82595737
GRCh38: 7:82966421-82966421
11 PCLO NM_033026.6(PCLO):c.4697A>G (p.Asp1566Gly) SNV Uncertain significance 1028493 GRCh37: 7:82585572-82585572
GRCh38: 7:82956256-82956256
12 PCLO NM_033026.6(PCLO):c.4892A>T (p.Asp1631Val) SNV Uncertain significance 1028494 GRCh37: 7:82585377-82585377
GRCh38: 7:82956061-82956061
13 PCLO NM_033026.6(PCLO):c.5621C>T (p.Pro1874Leu) SNV Uncertain significance 1029002 GRCh37: 7:82584648-82584648
GRCh38: 7:82955332-82955332
14 PCLO NM_033026.6(PCLO):c.6533C>A (p.Pro2178His) SNV Uncertain significance 1029003 GRCh37: 7:82583736-82583736
GRCh38: 7:82954420-82954420
15 PCLO NM_033026.6(PCLO):c.8069G>A (p.Gly2690Asp) SNV Uncertain significance 1029004 GRCh37: 7:82582200-82582200
GRCh38: 7:82952884-82952884
16 PCLO NM_033026.6(PCLO):c.9373G>A (p.Asp3125Asn) SNV Uncertain significance 1029005 GRCh37: 7:82580531-82580531
GRCh38: 7:82951215-82951215
17 PCLO NM_033026.6(PCLO):c.9494T>C (p.Leu3165Ser) SNV Uncertain significance 1029006 GRCh37: 7:82580410-82580410
GRCh38: 7:82951094-82951094
18 PCLO NM_033026.6(PCLO):c.9677T>C (p.Ile3226Thr) SNV Uncertain significance 1029007 GRCh37: 7:82580227-82580227
GRCh38: 7:82950911-82950911
19 PCLO NM_033026.6(PCLO):c.10780A>G (p.Thr3594Ala) SNV Uncertain significance 1031531 GRCh37: 7:82579124-82579124
GRCh38: 7:82949808-82949808
20 PCLO NM_033026.6(PCLO):c.11671T>C (p.Ser3891Pro) SNV Uncertain significance 1031532 GRCh37: 7:82545631-82545631
GRCh38: 7:82916315-82916315
21 PCLO NM_033026.6(PCLO):c.2576A>G (p.Gln859Arg) SNV Uncertain significance 1032311 GRCh37: 7:82764290-82764290
GRCh38: 7:83134974-83134974
22 PCLO NM_033026.6(PCLO):c.5267G>A (p.Arg1756His) SNV Uncertain significance 1032312 GRCh37: 7:82585002-82585002
GRCh38: 7:82955686-82955686
23 PCLO NM_033026.6(PCLO):c.6532C>T (p.Pro2178Ser) SNV Uncertain significance 1032313 GRCh37: 7:82583737-82583737
GRCh38: 7:82954421-82954421
24 PCLO NM_033026.6(PCLO):c.7375G>T (p.Val2459Phe) SNV Uncertain significance 1032314 GRCh37: 7:82582894-82582894
GRCh38: 7:82953578-82953578
25 PCLO NM_033026.6(PCLO):c.863T>G (p.Ile288Arg) SNV Uncertain significance 1032315 GRCh37: 7:82785094-82785094
GRCh38: 7:83155778-83155778

Expression for Pontocerebellar Hypoplasia, Type 3

Search GEO for disease gene expression data for Pontocerebellar Hypoplasia, Type 3.

Pathways for Pontocerebellar Hypoplasia, Type 3

GO Terms for Pontocerebellar Hypoplasia, Type 3

Cellular components related to Pontocerebellar Hypoplasia, Type 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 trans-Golgi network GO:0005802 8.62 TBC1D23 GSAP

Sources for Pontocerebellar Hypoplasia, Type 3

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-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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