MDLS
MCID: MLL018
MIFTS: 52

Miller-Dieker Lissencephaly Syndrome (MDLS)

Categories: Fetal diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Miller-Dieker Lissencephaly Syndrome

MalaCards integrated aliases for Miller-Dieker Lissencephaly Syndrome:

Name: Miller-Dieker Lissencephaly Syndrome 58 12 54 26 76 56 15 41
Miller-Dieker Syndrome 12 77 54 26 60
Mds 58 12 26 17
Mdls 58 54 76
Miller Dieker Syndrome 30 74
Lissencephaly Due to 17p13.3 Deletion 60
Classical Lissencephaly Syndrome 26
Classical Lissencephaly 74
Telomeric Deletion 17p 60
Monosomy 17p13.3 60

Characteristics:

Orphanet epidemiological data:

60
miller-dieker syndrome
Inheritance: Autosomal dominant; Prevalence: 1-9/100000 (Europe); Age of onset: Infancy,Neonatal;

OMIM:

58
Inheritance:
autosomal dominant

Miscellaneous:
contiguous gene syndrome
death often before age 2


HPO:

33
miller-dieker lissencephaly syndrome:
Inheritance contiguous gene syndrome autosomal dominant inheritance


Classifications:



Summaries for Miller-Dieker Lissencephaly Syndrome

OMIM : 58 Features of the Miller-Dieker syndrome include classic lissencephaly (pachygyria, incomplete or absent gyration of the cerebrum), microcephaly, wrinkled skin over the glabella and frontal suture, prominent occiput, narrow forehead, downward slanting palpebral fissures, small nose and chin, cardiac malformations, hypoplastic male extrenal genitalia, growth retardation, and mental deficiency with seizures and EEG abnormalities. Life expectancy is grossly reduced, with death most often occurring during early childhood (summary by Schinzel, 1988). Lissencephaly means 'smooth brain,' i.e., brain without convolutions or gyri. Deletion of or mutation in the LIS1 gene (PAFAH1B1; 601545) appears to cause the lissencephaly because point mutations have been identified in this gene in isolated lissencephaly sequence (ILS; see 607432). Facial dysmorphism and other anomalies in Miller-Dieker patients appear to be the consequence of deletion of additional genes distal to LIS1. Toyo-oka et al. (2003) presented evidence that the gene whose deletion is responsible for the greater severity of Miller-Dieker syndrome compared to isolated lissencephaly is the gene encoding 14-3-3-epsilon (YWHAE; 605066). (247200)

MalaCards based summary : Miller-Dieker Lissencephaly Syndrome, also known as miller-dieker syndrome, is related to pachygyria and lissencephaly, and has symptoms including seizures An important gene associated with Miller-Dieker Lissencephaly Syndrome is PAFAH1B1 (Platelet Activating Factor Acetylhydrolase 1b Regulatory Subunit 1), and among its related pathways/superpathways are IGF1 pathway and COPI-independent Golgi-to-ER retrograde traffic. Affiliated tissues include brain, heart and lung, and related phenotypes are intellectual disability and motor delay

Disease Ontology : 12 A syndrome characterized by classical lissencephaly and distinct facial features. Visible and submicroscopic deletions of 17p13.3, including the LIS1 gene, are found in almost 100% of patients.

Genetics Home Reference : 26 Miller-Dieker syndrome is a condition characterized by a pattern of abnormal brain development known as lissencephaly. Normally the exterior of the brain (cerebral cortex) is multi-layered with folds and grooves. People with lissencephaly have an abnormally smooth brain with fewer folds and grooves. These brain malformations cause severe intellectual disability, developmental delay, seizures, abnormal muscle stiffness (spasticity), weak muscle tone (hypotonia), and feeding difficulties. Seizures usually begin before six months of age, and some occur from birth. Typically, the smoother the surface of the brain is, the more severe the associated symptoms are.

NIH Rare Diseases : 54 Miller-Dieker syndrome (MDS) is a genetic condition characterized by a specific brain malformation (lissencephaly); distinctive facial features; and severe neurologic abnormalities including intellectual disability and seizures. Very few affected children survive beyond childhood. MDS is caused by a deletion (missing piece) of genetic material on the short arm of chromosome 17 (17p). Most cases are not inherited and occur randomly. In some cases, it is caused by inheriting a chromosome rearrangement (balanced translocation) from an unaffected parent. Treatment is based on the symptoms in each person and aims to prevent complications and control seizures.

UniProtKB/Swiss-Prot : 76 Miller-Dieker lissencephaly syndrome: A contiguous gene deletion syndrome of chromosome 17p13.3, characterized by classical lissencephaly and distinct facial features. Additional congenital malformations can be part of the condition.

Wikipedia : 77 Miller–Dieker syndrome (abbreviated MDS), Miller–Dieker lissencephaly syndrome (MDLS), and chromosome... more...

Related Diseases for Miller-Dieker Lissencephaly Syndrome

Diseases related to Miller-Dieker Lissencephaly Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 447)
# Related Disease Score Top Affiliating Genes
1 pachygyria 30.5 PAFAH1B1 TUBA1A
2 lissencephaly 30.0 FKTN NUDC PAFAH1B1 PAFAH1B2 TUBA1A YWHAE
3 physical disorder 28.9 FLNA PAFAH1B1 TUBA1A
4 myelodysplastic syndrome 12.2
5 muscular dystrophy 11.9
6 epidermolysa bullosa simplex with muscular dystrophy 11.8
7 myelodysplastic syndrome with excess blasts 11.7
8 walker-warburg syndrome 11.7
9 muscular dystrophy-dystroglycanopathy , type a, 1 11.5
10 chromosome 5q deletion syndrome 11.4
11 dystonia 11, myoclonic 11.4
12 epidermolysis bullosa simplex with muscular dystrophy 11.3
13 aplastic anemia 11.3
14 juvenile myelomonocytic leukemia 11.3
15 distal 17p13.3 microdeletion syndrome 11.2
16 myelodysplastic myeloproliferative cancer 11.2
17 muscular dystrophy, duchenne and becker type 11.2
18 meniere disease 11.2
19 atypical chronic myeloid leukemia 11.2
20 madelung deformity 11.2
21 menkes disease 11.1
22 townes-brocks syndrome 11.1
23 spondyloepimetaphyseal dysplasia with joint laxity, type 2 11.0
24 muscular dystrophy, congenital, lmna-related 11.0
25 lama2-related muscular dystrophy 11.0
26 mpv17-related hepatocerebral mitochondrial dna depletion syndrome 11.0
27 ocular muscular dystrophy 11.0
28 ophthalmoplegic muscular dystrophy 11.0
29 metatropic dysplasia 10.9
30 facioscapulohumeral muscular dystrophy 1 10.9
31 mitochondrial dna depletion syndrome 4a 10.9
32 monosomy 7 of bone marrow 10.9
33 adrenomyodystrophy 10.9
34 epidermolysis bullosa simplex with pyloric atresia 10.9
35 reynolds syndrome 10.9
36 pulmonary fibrosis and/or bone marrow failure, telomere-related, 1 10.9
37 myeloproliferative/lymphoproliferative neoplasms, familial 10.9
38 hereditary lymphedema 10.9
39 hereditary lymphedema i 10.9
40 mitochondrial dna depletion syndrome 10.9
41 leukemia 10.6
42 heart disease 10.5
43 myeloid leukemia 10.4
44 leukemia, acute myeloid 10.4
45 retinitis pigmentosa 10.4
46 leber congenital amaurosis 4 10.4
47 retinitis 10.4
48 polyhydramnios 10.4
49 xp22.3 microdeletion syndrome 10.3
50 emphysema, congenital lobar 10.2

Graphical network of the top 20 diseases related to Miller-Dieker Lissencephaly Syndrome:



Diseases related to Miller-Dieker Lissencephaly Syndrome

Symptoms & Phenotypes for Miller-Dieker Lissencephaly Syndrome

Human phenotypes related to Miller-Dieker Lissencephaly Syndrome:

33 60 (show top 50) (show all 58)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 33 obligate (100%) HP:0001249
2 motor delay 33 obligate (100%) HP:0001270
3 seizures 60 33 hallmark (90%) Very frequent (99-80%) HP:0001250
4 eeg abnormality 60 33 hallmark (90%) Very frequent (99-80%) HP:0002353
5 short nose 60 33 very rare (1%) Very frequent (99-80%) HP:0003196
6 anteverted nares 60 33 hallmark (90%) Very frequent (99-80%) HP:0000463
7 epicanthus 60 33 very rare (1%) Very frequent (99-80%) HP:0000286
8 growth delay 60 33 hallmark (90%) Very frequent (99-80%) HP:0001510
9 cerebral cortical atrophy 60 33 hallmark (90%) Very frequent (99-80%) HP:0002120
10 high forehead 60 33 hallmark (90%) Very frequent (99-80%) HP:0000348
11 lissencephaly 60 33 very rare (1%) Very frequent (99-80%) HP:0001339
12 abnormality of upper lip 60 33 hallmark (90%) Very frequent (99-80%) HP:0000177
13 frontal bossing 33 hallmark (90%) HP:0002007
14 posteriorly rotated ears 33 hallmark (90%) HP:0000358
15 abnormality of the cardiovascular system 60 33 frequent (33%) Frequent (79-30%) HP:0001626
16 polyhydramnios 60 33 very rare (1%) Frequent (79-30%) HP:0001561
17 ataxia 60 33 occasional (7.5%) Occasional (29-5%) HP:0001251
18 nephropathy 60 33 occasional (7.5%) Occasional (29-5%) HP:0000112
19 clinodactyly of the 5th finger 60 33 very rare (1%) Occasional (29-5%) HP:0004209
20 sacral dimple 60 33 very rare (1%) Occasional (29-5%) HP:0000960
21 omphalocele 60 33 occasional (7.5%) Occasional (29-5%) HP:0001539
22 hypoplasia of the corpus callosum 60 33 very rare (1%) Occasional (29-5%) HP:0002079
23 low-set ears 33 very rare (1%) HP:0000369
24 wide nasal bridge 33 very rare (1%) HP:0000431
25 microcephaly 33 very rare (1%) HP:0000252
26 micrognathia 33 very rare (1%) HP:0000347
27 intrauterine growth retardation 33 very rare (1%) HP:0001511
28 thick upper lip vermilion 33 very rare (1%) HP:0000215
29 abnormality of cardiovascular system morphology 33 very rare (1%) HP:0030680
30 deep palmar crease 33 very rare (1%) HP:0006191
31 single transverse palmar crease 33 very rare (1%) HP:0000954
32 midline brain calcifications 33 very rare (1%) HP:0007045
33 joint contracture of the hand 33 very rare (1%) HP:0009473
34 cavum septum pellucidum 33 very rare (1%) HP:0002389
35 failure to thrive 33 HP:0001508
36 inguinal hernia 33 HP:0000023
37 cataract 33 HP:0000518
38 abnormality of metabolism/homeostasis 33 HP:0001939
39 cleft palate 33 HP:0000175
40 delayed eruption of teeth 33 HP:0000684
41 cryptorchidism 33 HP:0000028
42 upslanted palpebral fissure 33 HP:0000582
43 thin upper lip vermilion 33 HP:0000219
44 pelvic kidney 33 HP:0000125
45 midface retrusion 33 HP:0011800
46 decreased fetal movement 33 HP:0001558
47 pachygyria 33 HP:0001302
48 infantile spasms 33 HP:0012469
49 progressive spastic paraplegia 33 HP:0007020
50 heterotopia 33 HP:0002282

Symptoms via clinical synopsis from OMIM:

58
Head And Neck Ears:
low-set ears
posteriorly rotated ears

Neurologic Central Nervous System:
seizures
pachygyria
infantile spasms
progressive spastic paraplegia
midline brain calcifications
more
Abdomen External Features:
inguinal hernia

Head And Neck Head:
microcephaly

Head And Neck Face:
micrognathia
bitemporal hollowing
furrowing of forehead

Growth Height:
intrauterine growth retardation

Genitourinary Kidneys:
pelvic kidney
cystic kidney

Respiratory Lung:
aspiration pneumonia

Head And Neck Nose:
small nose
upturned nares

Prenatal Manifestations Movement:
decreased fetal activity

Laboratory Abnormalities:
cytogenetic deletion of chromosome 17p13.3
fluorescence in situ hybridization specific probe for mds critical region

Skeletal Hands:
clinodactyly
camptodactyly
polydactyly
transverse palmar creases

Growth Other:
failure to thrive

Head And Neck Eyes:
cataract
upslanting palpebral fissures

Head And Neck Mouth:
cleft palate
thin vermilion border of upper lip
prominent upper lip

Genitourinary Internal Genitalia Male:
cryptorchidism

Prenatal Manifestations Amniotic Fluid:
polyhydramnios

Abdomen Gastrointestinal:
omphalocele
duodenal atresia

Cardiovascular Heart:
congenital heart defect

Skin Nails Hair Skin:
transverse palmar creases

Head And Neck Teeth:
late tooth eruption

Clinical features from OMIM:

247200

UMLS symptoms related to Miller-Dieker Lissencephaly Syndrome:


seizures

MGI Mouse Phenotypes related to Miller-Dieker Lissencephaly Syndrome:

47
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 9.91 BHLHA9 DPH1 FKTN FLNA PAFAH1B1 PAFAH1B2
2 craniofacial MP:0005382 9.63 AKAP10 CRK DPH1 FLNA HIC1 KIF1BP
3 embryo MP:0005380 9.56 AKAP10 DPH1 FKTN HIC1 KIF1BP PAFAH1B1
4 nervous system MP:0003631 9.36 AKAP10 CRK DPH1 FKTN FLNA HIC1

Drugs & Therapeutics for Miller-Dieker Lissencephaly Syndrome

Search Clinical Trials , NIH Clinical Center for Miller-Dieker Lissencephaly Syndrome

Genetic Tests for Miller-Dieker Lissencephaly Syndrome

Genetic tests related to Miller-Dieker Lissencephaly Syndrome:

# Genetic test Affiliating Genes
1 Miller Dieker Syndrome 30

Anatomical Context for Miller-Dieker Lissencephaly Syndrome

MalaCards organs/tissues related to Miller-Dieker Lissencephaly Syndrome:

42
Brain, Heart, Lung, Skin, Liver, Bone, Cortex

Publications for Miller-Dieker Lissencephaly Syndrome

Articles related to Miller-Dieker Lissencephaly Syndrome:

(show all 12)
# Title Authors Year
1
Electroclinical Pattern and Epilepsy Evolution in an Infant with Miller-Dieker Syndrome. ( 30271461 )
2018
2
Array comparative genomic hybridization characterization of a 3.3-Mb 17p13.3-p13.2 deletion encompassing YWHAE, CRK, HIC1 and PAFAH1B1 in an 8-year-old girl with Miller-Dieker lissencephaly syndrome, congenital heart defects, growth restriction and developmental delay. ( 30342670 )
2018
3
Miller-Dieker Syndrome with unbalanced translocation 45, X, psu dic(17;Y)(p13;p11.32) detected by fluorescence in situ hybridization and G-banding analysis using high resolution banding technique. ( 27644460 )
2017
4
An Organoid-Based Model of Cortical Development Identifies Non-Cell-Autonomous Defects in Wnt Signaling Contributing to Miller-Dieker Syndrome. ( 28380362 )
2017
5
Miller-Dieker Syndrome due to a 5.5-Mb 17p Deletion in a 17;Y Pseudodicentric Chromosome. ( 28738335 )
2017
6
A Case of Concurrent Miller-Dieker Syndrome (17p13.3 Deletion) and 22q11.2 Deletion Syndrome. ( 27617133 )
2015
7
Management of general anesthesia in a child with Miller-Dieker syndrome: a case report. ( 29497646 )
2015
8
Ventriculomegaly, intrauterine growth restriction, and congenital heart defects as salient prenatal sonographic findings of Miller-Dieker lissencephaly syndrome associated with monosomy 17p (17p13.2 --> pter) in a fetus. ( 20466299 )
2010
9
Prenatal diagnosis of monosomy 17p (17p13.3-->pter) associated with polyhydramnios, intrauterine growth restriction, ventriculomegaly, and Miller-Dieker lissencephaly syndrome in a fetus. ( 20045764 )
2009
10
Expression map of human chromosome region 17p13.3, spanning the RP13 dominant retinitis pigmentosa locus, the Miller-Dieker lissencephaly syndrome (MDLS) region, and a putative tumour suppressor locus. ( 10828595 )
2000
11
Prenatal diagnosis of lissencephaly: Miller-Dieker syndrome. ( 7806665 )
1994
12
A spectrum of gyral anomalies in Miller-Dieker (lissencephaly) syndrome. ( 6834190 )
1983

Variations for Miller-Dieker Lissencephaly Syndrome

Copy number variations for Miller-Dieker Lissencephaly Syndrome from CNVD:

7
# CNVD ID Chromosom Start End Type Gene Symbol CNVD Disease
1 13774 1 1 3600000 Copy number Miller-Dieker syndrome
2 106777 17 1 22200000 Copy number PAFAH1B1 Miller-Dieker syndrome
3 106851 17 1 3600000 Deletion LIS1 Miller-Dieker syndrome
4 106866 17 1 3600000 Microdeletion Miller-Dieker lissencephaly syndrome

Expression for Miller-Dieker Lissencephaly Syndrome

Search GEO for disease gene expression data for Miller-Dieker Lissencephaly Syndrome.

Pathways for Miller-Dieker Lissencephaly Syndrome

Pathways related to Miller-Dieker Lissencephaly Syndrome according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.6 CRK YWHAE
2 10.58 PAFAH1B1 PAFAH1B2 PAFAH1B3
3 10.51 NUDC PAFAH1B1 PAFAH1B2 PAFAH1B3 YWHAE

GO Terms for Miller-Dieker Lissencephaly Syndrome

Cellular components related to Miller-Dieker Lissencephaly Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nucleus GO:0005634 9.93 BHLHA9 CAMTA2 CRK DPH1 FKTN FLNA
2 extracellular exosome GO:0070062 9.87 CRK FLNA PAFAH1B1 PAFAH1B2 RTN4RL1 TUBA1A
3 cytosol GO:0005829 9.7 AKAP10 CRK DPH1 FLNA HIC1 NUDC
4 central region of growth cone GO:0090724 8.62 PAFAH1B1 YWHAE
5 cytoplasm GO:0005737 10.03 AKAP10 BHLHA9 CRK DPH1 FLNA KIF1BP

Biological processes related to Miller-Dieker Lissencephaly Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 G2/M transition of mitotic cell cycle GO:0000086 9.43 PAFAH1B1 TUBA1A YWHAE
2 positive regulation of substrate adhesion-dependent cell spreading GO:1900026 9.37 CRK FLNA
3 lipid catabolic process GO:0016042 9.33 PAFAH1B1 PAFAH1B2 PAFAH1B3
4 negative regulation of JNK cascade GO:0046329 9.32 FKTN PAFAH1B1
5 ciliary basal body-plasma membrane docking GO:0097711 9.13 PAFAH1B1 TUBA1A YWHAE
6 regulation of G2/M transition of mitotic cell cycle GO:0010389 8.8 PAFAH1B1 TUBA1A YWHAE

Molecular functions related to Miller-Dieker Lissencephaly Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein binding GO:0005515 9.55 AKAP10 BHLHA9 CAMTA2 CRK DPH1 FKTN
2 histone deacetylase binding GO:0042826 9.5 CAMTA2 HIC1 YWHAE
3 phospholipase A2 activity GO:0004623 9.33 PAFAH1B1 PAFAH1B2 PAFAH1B3
4 1-alkyl-2-acetylglycerophosphocholine esterase activity GO:0003847 9.26 PAFAH1B2 PAFAH1B3
5 platelet-activating factor acetyltransferase activity GO:0047179 8.96 PAFAH1B2 PAFAH1B3

Sources for Miller-Dieker Lissencephaly Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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