LIS9
MCID: LSS040
MIFTS: 32

Lissencephaly 9 with Complex Brainstem Malformation (LIS9)

Categories: Fetal diseases, Genetic diseases, Mental diseases, Neuronal diseases, Rare diseases
Data Licensing
For inquiries, contact:

Aliases & Classifications for Lissencephaly 9 with Complex Brainstem Malformation

MalaCards integrated aliases for Lissencephaly 9 with Complex Brainstem Malformation:

Name: Lissencephaly 9 with Complex Brainstem Malformation 57 11 73 28 5 14 38
Lis9 57 11 73
Posterior-Predominant Lissencephaly-Broad Flat Pons and Medulla-Midline Crossing Defects Syndrome 11 58

Characteristics:


Inheritance:

Lissencephaly 9 with Complex Brainstem Malformation: Autosomal dominant 57
Posterior-Predominant Lissencephaly-Broad Flat Pons and Medulla-Midline Crossing Defects Syndrome: Autosomal dominant 58

Prevelance:

Posterior-Predominant Lissencephaly-Broad Flat Pons and Medulla-Midline Crossing Defects Syndrome: <1/1000000 (Worldwide) 58

Age Of Onset:

Posterior-Predominant Lissencephaly-Broad Flat Pons and Medulla-Midline Crossing Defects Syndrome: Infancy 58

OMIM®:

57 (Updated 08-Dec-2022)
Miscellaneous:
onset in infancy
de novo mutation


Classifications:

Orphanet: 58  
Rare neurological diseases
Developmental anomalies during embryogenesis


Summaries for Lissencephaly 9 with Complex Brainstem Malformation

OMIM®: 57 Lissencephaly-9 with complex brainstem malformation (LIS9) is an autosomal dominant neurologic disorder characterized by global developmental delay apparent since infancy, impaired intellectual development with poor or absent speech, and sometimes abnormal or involuntary movements associated with abnormal brain imaging that typically shows pachygyria, lissencephaly, and malformation of the brainstem consistent with a neuronal migration defect (summary by Dobyns et al., 2018). For a general description and a discussion of genetic heterogeneity of lissencephaly, see LIS1 (607432). (618325) (Updated 08-Dec-2022)

MalaCards based summary: Lissencephaly 9 with Complex Brainstem Malformation, also known as lis9, is related to motility-related diarrhea. An important gene associated with Lissencephaly 9 with Complex Brainstem Malformation is MACF1 (Microtubule Actin Crosslinking Factor 1). Affiliated tissues include pons, cortex and brain, and related phenotypes are involuntary movements and microcephaly

UniProtKB/Swiss-Prot: 73 A form of lissencephaly, a disorder of cortical development characterized by agyria or pachygyria and disorganization of the clear neuronal lamination of normal six-layered cortex. LIS9 is an autosomal dominant form clinically characterized by global developmental delay apparent since infancy, impaired intellectual development with poor or absent speech, and sometimes abnormal or involuntary movements. Brain imaging shows malformation of the brainstem, in addition to pachygyria and lissencephaly.

Disease Ontology: 11 A lissencephaly characterized by global developmental delay, impaired intellectual development with poor or absent speech, pachygyria, lissencephaly, and malformation of the brainstem that has material basis in heterozygous mutation in MACF1 on chromosome 1p34.3.

Related Diseases for Lissencephaly 9 with Complex Brainstem Malformation

Diseases related to Lissencephaly 9 with Complex Brainstem Malformation via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 motility-related diarrhea 9.6 PDZD2 NHERF4

Symptoms & Phenotypes for Lissencephaly 9 with Complex Brainstem Malformation

Human phenotypes related to Lissencephaly 9 with Complex Brainstem Malformation:

58 30 (show all 29)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 involuntary movements 58 30 Very rare (1%) Frequent (79-30%)
HP:0004305
2 microcephaly 30 Very rare (1%) HP:0000252
3 short stature 30 Very rare (1%) HP:0004322
4 spasticity 58 30 Occasional (29-5%)
HP:0001257
5 dysphagia 58 30 Frequent (79-30%)
HP:0002015
6 strabismus 58 30 Frequent (79-30%)
HP:0000486
7 facial asymmetry 58 30 Occasional (29-5%)
HP:0000324
8 pachygyria 58 30 Very frequent (99-80%)
HP:0001302
9 seizure 30 HP:0001250
10 global developmental delay 30 HP:0001263
11 stereotypy 58 Occasional (29-5%)
12 intellectual disability, severe 58 Very frequent (99-80%)
13 absent speech 30 HP:0001344
14 neurodevelopmental delay 58 Very frequent (99-80%)
15 aplasia/hypoplasia of the cerebellum 58 Very frequent (99-80%)
16 hip dislocation 58 Occasional (29-5%)
17 cerebellar hypoplasia 30 HP:0001321
18 infantile spasms 58 Occasional (29-5%)
19 generalized hypotonia 30 HP:0001290
20 hypoplasia of the corpus callosum 30 HP:0002079
21 muscular hypotonia of the trunk 58 Very frequent (99-80%)
22 optic nerve hypoplasia 58 Occasional (29-5%)
23 cerebral visual impairment 58 Occasional (29-5%)
24 neurogenic bladder 58 Occasional (29-5%)
25 abnormal hippocampus morphology 58 Very frequent (99-80%)
26 hypoplasia of the brainstem 30 HP:0002365
27 myoclonic seizure 58 Occasional (29-5%)
28 abnormality of the anterior commissure 58 Very frequent (99-80%)
29 thin corpus callosum 58 Frequent (79-30%)

Symptoms via clinical synopsis from OMIM®:

57 (Updated 08-Dec-2022)
Abdomen Gastrointestinal:
dysphagia

Neurologic Central Nervous System:
global developmental delay
thin corpus callosum
brainstem hypoplasia
poor or absent speech
impaired intellectual development, severe
more
Head And Neck Face:
facial asymmetry

Head And Neck Head:
microcephaly (-4 to 5 sd) (in some patients)

Muscle Soft Tissue:
hypotonia

Head And Neck Eyes:
strabismus
impaired extraocular movements

Growth Height:
short stature (in some patients)

Clinical features from OMIM®:

618325 (Updated 08-Dec-2022)

Drugs & Therapeutics for Lissencephaly 9 with Complex Brainstem Malformation

Search Clinical Trials, NIH Clinical Center for Lissencephaly 9 with Complex Brainstem Malformation

Genetic Tests for Lissencephaly 9 with Complex Brainstem Malformation

Genetic tests related to Lissencephaly 9 with Complex Brainstem Malformation:

# Genetic test Affiliating Genes
1 Lissencephaly 9 with Complex Brainstem Malformation 28 MACF1

Anatomical Context for Lissencephaly 9 with Complex Brainstem Malformation

Organs/tissues related to Lissencephaly 9 with Complex Brainstem Malformation:

MalaCards : Pons, Cortex, Brain, Cerebellum

Publications for Lissencephaly 9 with Complex Brainstem Malformation

Articles related to Lissencephaly 9 with Complex Brainstem Malformation:

# Title Authors PMID Year
1
MACF1 Mutations Encoding Highly Conserved Zinc-Binding Residues of the GAR Domain Cause Defects in Neuronal Migration and Axon Guidance. 57 5
30471716 2018
2
Pontine malformation, undecussated pyramidal tracts, and regional polymicrogyria: a new syndrome. 57 5
24507697 2014
3
Duplication in the microtubule-actin cross-linking factor 1 gene causes a novel neuromuscular condition. 57
24899269 2014

Variations for Lissencephaly 9 with Complex Brainstem Malformation

ClinVar genetic disease variations for Lissencephaly 9 with Complex Brainstem Malformation:

5 (show all 48)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 MACF1 NM_001394062.1(MACF1):c.20293G>C (p.Gly6765Arg) SNV Pathogenic
586953 rs1488808726 GRCh37: 1:39916758-39916758
GRCh38: 1:39451086-39451086
2 MACF1 NM_012090.5(MACF1):c.10617+444_15577-288del DEL Pathogenic
586952 GRCh37: 1:39894403-39933999
GRCh38: 1:39428731-39468327
3 MACF1 NM_001394062.1(MACF1):c.21884G>T (p.Cys7295Phe) SNV Pathogenic
586951 rs1557670520 GRCh37: 1:39934399-39934399
GRCh38: 1:39468727-39468727
4 MACF1 NM_001394062.1(MACF1):c.21883T>G (p.Cys7295Gly) SNV Pathogenic
586950 rs1557670515 GRCh37: 1:39934398-39934398
GRCh38: 1:39468726-39468726
5 MACF1 NM_001394062.1(MACF1):c.21877G>T (p.Asp7293Tyr) SNV Pathogenic
586949 rs1557670503 GRCh37: 1:39934392-39934392
GRCh38: 1:39468720-39468720
6 MACF1 NM_001394062.1(MACF1):c.21707G>T (p.Cys7236Phe) SNV Pathogenic
586948 rs1557668270 GRCh37: 1:39929312-39929312
GRCh38: 1:39463640-39463640
7 MACF1 NM_001394062.1(MACF1):c.12265C>T (p.Gln4089Ter) SNV Pathogenic
1685933 GRCh37: 1:39826485-39826485
GRCh38: 1:39360813-39360813
8 MACF1 NM_001394062.1(MACF1):c.21717G>T (p.Arg7239Ser) SNV Likely Pathogenic
1694447 GRCh37: 1:39929322-39929322
GRCh38: 1:39463650-39463650
9 MACF1 NM_001394062.1(MACF1):c.1957C>T (p.Leu653Phe) SNV Likely Pathogenic
1676542 GRCh37:
GRCh38:
10 MACF1 NM_001394062.1(MACF1):c.21803G>A (p.Arg7268His) SNV Likely Pathogenic
1699453 GRCh37: 1:39934318-39934318
GRCh38: 1:39468646-39468646
11 MACF1 NM_001394062.1(MACF1):c.11099A>G (p.Gln3700Arg) SNV Uncertain Significance
1709215 GRCh37: 1:39816590-39816590
GRCh38: 1:39350918-39350918
12 MACF1 NM_001394062.1(MACF1):c.20105T>C (p.Leu6702Pro) SNV Uncertain Significance
828140 rs1570118657 GRCh37: 1:39914282-39914282
GRCh38: 1:39448610-39448610
13 MACF1 NM_001394062.1(MACF1):c.21604G>C (p.Glu7202Gln) SNV Uncertain Significance
930636 rs1644564326 GRCh37: 1:39927635-39927635
GRCh38: 1:39461963-39461963
14 MACF1 NM_001394062.1(MACF1):c.19229T>C (p.Met6410Thr) SNV Uncertain Significance
930813 rs1644147317 GRCh37: 1:39908510-39908510
GRCh38: 1:39442838-39442838
15 MACF1 NM_001394062.1(MACF1):c.19070C>T (p.Pro6357Leu) SNV Uncertain Significance
930824 rs1190036986 GRCh37: 1:39908205-39908205
GRCh38: 1:39442533-39442533
16 MACF1 NM_001394062.1(MACF1):c.3450-7C>G SNV Uncertain Significance
931110 rs1646412588 GRCh37: 1:39782056-39782056
GRCh38: 1:39316384-39316384
17 MACF1 NM_001394062.1(MACF1):c.20952T>G (p.Asn6984Lys) SNV Uncertain Significance
931697 rs201053350 GRCh37: 1:39920646-39920646
GRCh38: 1:39454974-39454974
18 MACF1 NM_001394062.1(MACF1):c.3838G>A (p.Gly1280Arg) SNV Uncertain Significance
1696588 GRCh37: 1:39784180-39784180
GRCh38: 1:39318508-39318508
19 MACF1 NM_001394062.1(MACF1):c.2870A>G (p.Tyr957Cys) SNV Uncertain Significance
1696644 GRCh37: 1:39775322-39775322
GRCh38: 1:39309650-39309650
20 MACF1 NM_001394062.1(MACF1):c.19053A>T (p.Arg6351Ser) SNV Uncertain Significance
1698800 GRCh37: 1:39908188-39908188
GRCh38: 1:39442516-39442516
21 MACF1 NM_001394062.1(MACF1):c.3450G>A (p.Lys1150=) SNV Uncertain Significance
983011 rs147586507 GRCh37: 1:39782063-39782063
GRCh38: 1:39316391-39316391
22 MACF1 NM_001394062.1(MACF1):c.12301C>G (p.Leu4101Val) SNV Uncertain Significance
996842 rs138390862 GRCh37: 1:39826521-39826521
GRCh38: 1:39360849-39360849
23 MACF1 NM_001394062.1(MACF1):c.18544C>T (p.Pro6182Ser) SNV Uncertain Significance
1030222 rs762203931 GRCh37: 1:39906771-39906771
GRCh38: 1:39441099-39441099
24 MACF1 NM_001394062.1(MACF1):c.20910C>A (p.His6970Gln) SNV Uncertain Significance
1030223 rs1644407465 GRCh37: 1:39920604-39920604
GRCh38: 1:39454932-39454932
25 MACF1 NM_001394062.1(MACF1):c.2355+5G>A SNV Uncertain Significance
1030224 rs1645888490 GRCh37: 1:39761559-39761559
GRCh38: 1:39295887-39295887
26 MACF1 NM_001394062.1(MACF1):c.2875C>T (p.Arg959Cys) SNV Uncertain Significance
1031170 rs1241320476 GRCh37: 1:39775327-39775327
GRCh38: 1:39309655-39309655
27 MACF1 NM_001394062.1(MACF1):c.358C>G (p.Pro120Ala) SNV Uncertain Significance
1031171 rs1645074548 GRCh37: 1:39719970-39719970
GRCh38: 1:39254298-39254298
28 MACF1 NM_001394062.1(MACF1):c.3727A>G (p.Lys1243Glu) SNV Uncertain Significance
1031172 rs1646431784 GRCh37: 1:39783024-39783024
GRCh38: 1:39317352-39317352
29 MACF1 NM_001394062.1(MACF1):c.3745G>T (p.Glu1249Ter) SNV Uncertain Significance
1031173 rs770263434 GRCh37: 1:39783042-39783042
GRCh38: 1:39317370-39317370
30 MACF1 NM_001394062.1(MACF1):c.4099C>T (p.Arg1367Cys) SNV Uncertain Significance
1031174 rs771527845 GRCh37: 1:39788349-39788349
GRCh38: 1:39322677-39322677
31 MACF1 NM_001394062.1(MACF1):c.15571G>T (p.Gly5191Trp) SNV Uncertain Significance
1031175 rs1641883203 GRCh37: 1:39854085-39854085
GRCh38: 1:39388413-39388413
32 MACF1 NM_001394062.1(MACF1):c.19416G>C (p.Gln6472His) SNV Uncertain Significance
1098676 GRCh37: 1:39909231-39909231
GRCh38: 1:39443559-39443559
33 MACF1 NM_001394062.1(MACF1):c.13780A>C (p.Met4594Leu) SNV Uncertain Significance
1184994 GRCh37: 1:39847756-39847756
GRCh38: 1:39382084-39382084
34 MACF1 NM_001394062.1(MACF1):c.19924G>C (p.Glu6642Gln) SNV Uncertain Significance
1299672 GRCh37: 1:39913526-39913526
GRCh38: 1:39447854-39447854
35 MACF1 NM_001394062.1(MACF1):c.1817A>T (p.Asp606Val) SNV Uncertain Significance
1301696 GRCh37: 1:39757613-39757613
GRCh38: 1:39291941-39291941
36 MACF1 NM_001394062.1(MACF1):c.7194C>A (p.Ala2398=) SNV Uncertain Significance
1319797 GRCh37: 1:39799454-39799454
GRCh38: 1:39333782-39333782
37 MACF1 NM_001394062.1(MACF1):c.744G>T (p.Glu248Asp) SNV Uncertain Significance
1325546 GRCh37: 1:39748909-39748909
GRCh38: 1:39283237-39283237
38 MACF1 NM_001394062.1(MACF1):c.20593C>T (p.Leu6865Phe) SNV Uncertain Significance
1333962 GRCh37: 1:39918002-39918002
GRCh38: 1:39452330-39452330
39 MACF1 NM_001394062.1(MACF1):c.15561AGA[2] (p.Glu5190del) MICROSAT Uncertain Significance
1341853 GRCh37: 1:39854075-39854077
GRCh38: 1:39388403-39388405
40 MACF1 NM_001394062.1(MACF1):c.1163C>T (p.Pro388Leu) SNV Uncertain Significance
1341866 GRCh37: 1:39750786-39750786
GRCh38: 1:39285114-39285114
41 MACF1 NM_001394062.1(MACF1):c.20591G>A (p.Arg6864Gln) SNV Uncertain Significance
1342415 GRCh37: 1:39918000-39918000
GRCh38: 1:39452328-39452328
42 MACF1 NM_001394062.1(MACF1):c.18866C>T (p.Thr6289Met) SNV Uncertain Significance
1342449 GRCh37: 1:39907910-39907910
GRCh38: 1:39442238-39442238
43 MACF1 NM_001394062.1(MACF1):c.12752A>G (p.His4251Arg) SNV Uncertain Significance
1342460 GRCh37: 1:39827330-39827330
GRCh38: 1:39361658-39361658
44 MACF1 NM_001394062.1(MACF1):c.12581G>A (p.Ser4194Asn) SNV Uncertain Significance
1342609 GRCh37: 1:39827159-39827159
GRCh38: 1:39361487-39361487
45 MACF1 NM_001394062.1(MACF1):c.12983G>A (p.Arg4328Gln) SNV Likely Benign
1049200 GRCh37: 1:39835746-39835746
GRCh38: 1:39370074-39370074
46 MACF1 NM_001394062.1(MACF1):c.1799G>A (p.Arg600Gln) SNV Likely Benign
982710 rs139794027 GRCh37: 1:39757595-39757595
GRCh38: 1:39291923-39291923
47 MACF1 NM_001394062.1(MACF1):c.756G>A (p.Gln252=) SNV Benign
1264063 GRCh37: 1:39748921-39748921
GRCh38: 1:39283249-39283249
48 MACF1 NM_001394062.1(MACF1):c.20186G>C (p.Ser6729Thr) SNV Benign
1277352 GRCh37: 1:39914363-39914363
GRCh38: 1:39448691-39448691

UniProtKB/Swiss-Prot genetic disease variations for Lissencephaly 9 with Complex Brainstem Malformation:

73
# Symbol AA change Variation ID SNP ID
1 MACF1 p.Cys7135Phe VAR_081967 rs1557668270
2 MACF1 p.Asp7186Tyr VAR_081968 rs1557670503
3 MACF1 p.Cys7188Phe VAR_081969 rs1557670520
4 MACF1 p.Cys7188Gly VAR_081970 rs1557670515

Expression for Lissencephaly 9 with Complex Brainstem Malformation

Search GEO for disease gene expression data for Lissencephaly 9 with Complex Brainstem Malformation.

Pathways for Lissencephaly 9 with Complex Brainstem Malformation

GO Terms for Lissencephaly 9 with Complex Brainstem Malformation

Sources for Lissencephaly 9 with Complex Brainstem Malformation

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
Content
Loading form....