PHMDS
MCID: PHL006
MIFTS: 61

Phelan-Mcdermid Syndrome (PHMDS)

Categories: Cardiovascular diseases, Fetal diseases, Genetic diseases, Neuronal diseases, Rare diseases, Skin diseases

Aliases & Classifications for Phelan-Mcdermid Syndrome

MalaCards integrated aliases for Phelan-Mcdermid Syndrome:

Name: Phelan-Mcdermid Syndrome 56 12 24 52 25 58 73 36 13 15 39
22q13.3 Deletion Syndrome 12 24 52 25 29 6 71
Chromosome 22q13.3 Deletion Syndrome 56 24 52 73
Telomeric 22q13 Monosomy Syndrome 56 73 71
Deletion 22q13.3 Syndrome 52 25
Deletion 22q13 Syndrome 24 25
Chromosome Deletion 43 71
22q13.3 Deletion 52 58
Monosomy 22q13.3 52 58
Monosomy 22q13 52 25
Phmds 56 73
Monosomy 22q13 Syndrome 12
22q13 Deletion Syndrome 25
22q13 Deletion 52

Characteristics:

Orphanet epidemiological data:

58
monosomy 22q13.3
Inheritance: Not applicable; Age of onset: Infancy,Neonatal;

OMIM:

56
Inheritance:
autosomal dominant

Miscellaneous:
de novo mutation
wide phenotypic variation
some patients do not have dysmorphic features
contiguous gene syndrome caused by deletion (160kb to 9mb) of 22q13.3 (in some patients)


HPO:

31
phelan-mcdermid syndrome:
Inheritance autosomal dominant inheritance sporadic


GeneReviews:

24
Penetrance Although it was previously thought that features of phelan-mcdermid syndrome were apparent in all individuals with non-mosaic 22q13.3 deletion that include shank3, recent evidence suggests that small deletions involving shank3 may be associated with non-penetrance and variable expressivity (see tabet et al [2017]). pathogenic variants in shank3 have been associated with phelan-mcdermid syndrome, nonsyndromic autism, and schizophrenia....

Classifications:

Orphanet: 58  
Rare neurological diseases
Rare circulatory system diseases
Rare skin diseases
Developmental anomalies during embryogenesis


Summaries for Phelan-Mcdermid Syndrome

NIH Rare Diseases : 52 22q13.3 deletion syndrome , also known as Phelan-McDermid syndrome, is a chromosome disorder caused by the loss (deletion ) of a small piece of chromosome 22 . The deletion occurs near the end of the long arm (or q arm) of the chromosome at a location designated as q13.3. Not everyone with 22q13.3 deletion syndrome will have the same medical, developmental, or behavioral problems (features). Common problems include low muscle tone (hypotonia ), intellectual disability , developmental delays especially delayed or absent speech , and tendency to overheat. Children may be tall and thin. Differences in other physical features are usually mild and may include long eyelashes, down slanting eyes, large ears, ears without normal folding, bulb-like tip of nose, pointed chin, large hands, and toenails that flake off as infants and then become hard and brittle as age. Additional medical problems may include gastrointestinal problems such as chronic diarrhea , constipation , or gastroesophageal reflux , seizures , delayed fine motor skills , changes in the way the brain developed, kidney problems especially vesicoureteral reflux (VUR) , vision problems such as strabismus, swelling of arms or legs (lymphedema ) during teen years, and recurrent infections, especially ear infections . Unusual behaviors may include mouthing or chewing on non-food items, decreased perception of pain, and autistic -like behaviors such as flapping of hands and repetitive motions. Most reported cases of 22q13.3 deletion syndrome are caused by 22q13.3 deletions, which usually includes many genes . The loss or the variation (mutation ) of a particular gene on chromosome 22, called the SHANK3 gene, is likely responsible for many of the common features associated with 22q13.3 deletion syndrome, especially intellectual disability, speech problems, low muscle tone, and developmental delay . Additional genes within the deleted area probably contribute to other features of the syndrome. In most cases, a larger deletion increases the number and severity of associated features, especially the severity of low muscle tone, developmental delay, differences in physical features, speech, and autism -like behavior. Smaller deletions located closer to the tip of the 22q seem to be associated with fewer medical, developmental, and behavioral problems.

MalaCards based summary : Phelan-Mcdermid Syndrome, also known as 22q13.3 deletion syndrome, is related to y chromosome infertility and partial deletion of y, and has symptoms including seizures and reflex, abnormal. An important gene associated with Phelan-Mcdermid Syndrome is SHANK3 (SH3 And Multiple Ankyrin Repeat Domains 3), and among its related pathways/superpathways are Glutamatergic synapse and Transmission across Chemical Synapses. The drugs Zinc and Mecasermin have been mentioned in the context of this disorder. Affiliated tissues include eye, kidney and brain, and related phenotypes are macrotia and delayed speech and language development

Disease Ontology : 12 A chromosome deletion syndrome that is has material basis in a deletion, translocation, ring chromosome formation or other structural change of the terminal end of chromosome 22 in the 22q13 region or a disease-causing mutation of the SHANK3 gene and that is characterized by neonatal hypotonia, absent to severely delayed speech, global developmental delay, and minor dysmorphic facial features. Most cases of 22q13.3 deletion syndrome are not inherited with 20% of cases (autosomal dominant) inherited from a parent. The deletion occurs most often as a random event during the formation of reproductive cells (eggs or sperm) or in early fetal development.

Genetics Home Reference : 25 22q13.3 deletion syndrome, which is also known as Phelan-McDermid syndrome, is a disorder caused by the loss of a small piece of chromosome 22. The deletion occurs near the end of the chromosome at a location designated q13.3. The features of 22q13.3 deletion syndrome vary widely and involve many parts of the body. Characteristic signs and symptoms include developmental delay, moderate to profound intellectual disability, decreased muscle tone (hypotonia), and absent or delayed speech. Some people with this condition have autism or autistic-like behavior that affects communication and social interaction, such as poor eye contact, sensitivity to touch, and aggressive behaviors. They may also chew on non-food items such as clothing. Less frequently, people with this condition have seizures or lose skills they had already acquired (developmental regression). Individuals with 22q13.3 deletion syndrome tend to have a decreased sensitivity to pain. Many also have a reduced ability to sweat, which can lead to a greater risk of overheating and dehydration. Some people with this condition have episodes of frequent vomiting and nausea (cyclic vomiting) and backflow of stomach acids into the esophagus (gastroesophageal reflux). People with 22q13.3 deletion syndrome typically have distinctive facial features, including a long, narrow head; prominent ears; a pointed chin; droopy eyelids (ptosis); and deep-set eyes. Other physical features seen with this condition include large and fleshy hands and/or feet, a fusion of the second and third toes (syndactyly), and small or abnormal toenails. Some affected individuals have rapid (accelerated) growth.

OMIM : 56 Phelan-McDermid syndrome is a developmental disorder with variable features. Common features include neonatal hypotonia, global developmental delay, normal to accelerated growth, absent to severely delayed speech, autistic behavior (see 209850), and minor dysmorphic features (Precht et al., 1998; Prasad et al., 2000; Durand et al., 2007). (606232)

KEGG : 36 Phelan-McDermid syndrome is a genetic disorder caused by a microdeletion on chromosome 22. It is characterized by severe expressive-language delay, mild mental retardation, hypotonia, joint laxity, dolichocephaly, and minor facial dysmorphisms. It has been indicated that this syndrome may also be caused by mutations in the SHANK3/PROSAP2 gene.

UniProtKB/Swiss-Prot : 73 Phelan-McDermid syndrome: A developmental disorder with variable features. Common features include neonatal hypotonia, global developmental delay, normal to accelerated growth, absent to severely delayed speech, autistic behavior, and minor dysmorphic features.

Wikipedia : 74 22q13 deletion syndrome, also known as Phelan-McDermid syndrome (PMS), is a genetic disorder caused by... more...

GeneReviews: NBK1198

Related Diseases for Phelan-Mcdermid Syndrome

Diseases related to Phelan-Mcdermid Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 346)
# Related Disease Score Top Affiliating Genes
1 y chromosome infertility 32.8 USP9Y RBMY1A1 DAZ1
2 partial deletion of y 32.6 USP9Y RBMY1A1 DAZ1
3 alacrima, achalasia, and mental retardation syndrome 31.2 UBE3A SHANK3 NRXN1 NLGN3 MECP2
4 azoospermia 30.4 USP9Y RBMY1A1 DAZ1 AZF1
5 male infertility 30.3 USP9Y RBMY1A1 DAZ1 AZF1
6 seizure disorder 30.3 NLGN1 MECP2
7 autism spectrum disorder 30.0 UBE3A SHANK3 SHANK2 SHANK1 NRXN1 NLGN4X
8 spermatogenic failure, y-linked, 2 29.9 USP9Y RBMY1A1 DAZ1
9 chromosomal deletion syndrome 29.7 SHANK2 SHANK1 NRXN1 MECP2
10 prader-willi syndrome 29.4 UBE3A SHOX MECP2 AZF1
11 autism 29.3 UBE3A SHANK3 SHANK2 SHANK1 NRXN1 NLGN4X
12 fragile x syndrome 29.0 UBE3A SHANK2 SHANK1 NRXN1 NLGN4X NLGN3
13 pervasive developmental disorder 28.3 UBE3A SHANK2 SHANK1 NRXN1 NLGN4X NLGN3
14 schizophrenia 27.9 SHANK3 SHANK2 NRXN1 NLGN4X NLGN1 MECP2
15 wolf-hirschhorn syndrome 11.4
16 ichthyosis, x-linked 11.3
17 cri-du-chat syndrome 11.3
18 trichorhinophalangeal syndrome, type ii 11.3
19 thrombocytopenia, paris-trousseau type 11.3
20 chromosome 15q13.3 deletion syndrome 11.3
21 malignant pleural mesothelioma 11.3
22 otodental dysplasia 11.1
23 hypotonia 11.0
24 hypoparathyroidism, sensorineural deafness, and renal disease 11.0
25 chromosome 5q deletion syndrome 11.0
26 chromosome 9p deletion syndrome 11.0
27 wilms tumor, aniridia, genitourinary anomalies, and mental retardation syndrome 11.0
28 van den bosch syndrome 11.0
29 chromosome 1p36 deletion syndrome 11.0
30 chromosome 10q26 deletion syndrome 11.0
31 chromosome 14q11-q22 deletion syndrome 11.0
32 chromosome 13q14 deletion syndrome 11.0
33 chromosome 15q25 deletion syndrome 11.0
34 chromosome 15q11.2 deletion syndrome 11.0
35 chromosome 15q24 deletion syndrome 11.0
36 major affective disorder 8 10.7
37 major affective disorder 9 10.7
38 bipolar disorder 10.7
39 lymphedema 10.7
40 neurofibromatosis, type iv, of riccardi 10.5
41 persistent mullerian duct syndrome, types i and ii 10.5
42 persistent mullerian duct syndrome 10.5
43 constipation 10.5
44 ring chromosome 22 10.5
45 ring chromosome 10.5
46 angelman syndrome 10.4
47 down syndrome 10.4
48 velocardiofacial syndrome 10.4
49 metachromatic leukodystrophy 10.4
50 abnormal hair, joint laxity, and developmental delay 10.4

Graphical network of the top 20 diseases related to Phelan-Mcdermid Syndrome:



Diseases related to Phelan-Mcdermid Syndrome

Symptoms & Phenotypes for Phelan-Mcdermid Syndrome

Human phenotypes related to Phelan-Mcdermid Syndrome:

58 31 (show top 50) (show all 84)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 macrotia 58 31 frequent (33%) Very frequent (99-80%) HP:0000400
2 delayed speech and language development 58 31 hallmark (90%) Very frequent (99-80%) HP:0000750
3 neonatal hypotonia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001319
4 hypoplastic toenails 58 31 frequent (33%) Very frequent (99-80%) HP:0001800
5 impaired pain sensation 58 31 frequent (33%) Very frequent (99-80%) HP:0007328
6 accelerated skeletal maturation 58 31 hallmark (90%) Very frequent (99-80%) HP:0005616
7 bruxism 58 31 frequent (33%) Very frequent (99-80%) HP:0003763
8 tall stature 31 hallmark (90%) HP:0000098
9 malar flattening 58 31 frequent (33%) Frequent (79-30%) HP:0000272
10 seizures 58 31 frequent (33%) Occasional (29-5%) HP:0001250
11 ptosis 58 31 frequent (33%) Frequent (79-30%) HP:0000508
12 dental malocclusion 58 31 frequent (33%) Occasional (29-5%) HP:0000689
13 wide nasal bridge 58 31 frequent (33%) Frequent (79-30%) HP:0000431
14 feeding difficulties 58 31 frequent (33%) Frequent (79-30%) HP:0011968
15 thick eyebrow 58 31 frequent (33%) Frequent (79-30%) HP:0000574
16 gastroesophageal reflux 58 31 frequent (33%) Occasional (29-5%) HP:0002020
17 full cheeks 58 31 frequent (33%) Frequent (79-30%) HP:0000293
18 immunodeficiency 58 31 frequent (33%) Frequent (79-30%) HP:0002721
19 dolichocephaly 58 31 frequent (33%) Frequent (79-30%) HP:0000268
20 hyperactivity 58 31 frequent (33%) Frequent (79-30%) HP:0000752
21 sacral dimple 58 31 frequent (33%) Frequent (79-30%) HP:0000960
22 strabismus 58 31 frequent (33%) Occasional (29-5%) HP:0000486
23 epicanthus 58 31 frequent (33%) Occasional (29-5%) HP:0000286
24 hypohidrosis 58 31 frequent (33%) Frequent (79-30%) HP:0000966
25 lymphedema 58 31 frequent (33%) Occasional (29-5%) HP:0001004
26 palpebral edema 58 31 frequent (33%) Frequent (79-30%) HP:0100540
27 deeply set eye 58 31 frequent (33%) Frequent (79-30%) HP:0000490
28 clinodactyly of the 5th finger 58 31 frequent (33%) Occasional (29-5%) HP:0004209
29 bulbous nose 58 31 frequent (33%) Frequent (79-30%) HP:0000414
30 autistic behavior 58 31 frequent (33%) Frequent (79-30%) HP:0000729
31 pointed chin 58 31 frequent (33%) Frequent (79-30%) HP:0000307
32 long eyelashes 58 31 frequent (33%) Frequent (79-30%) HP:0000527
33 large hands 58 31 frequent (33%) Frequent (79-30%) HP:0001176
34 high palate 31 frequent (33%) HP:0000218
35 long philtrum 31 frequent (33%) HP:0000343
36 autism 31 frequent (33%) HP:0000717
37 2-3 toe syndactyly 31 frequent (33%) HP:0004691
38 poor eye contact 31 frequent (33%) HP:0000817
39 unsteady gait 31 frequent (33%) HP:0002317
40 episodic vomiting 31 frequent (33%) HP:0002572
41 broad-based gait 31 frequent (33%) HP:0002136
42 heat intolerance 31 frequent (33%) HP:0002046
43 hyperorality 31 frequent (33%) HP:0000710
44 macrocephaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0000256
45 agenesis of corpus callosum 58 31 occasional (7.5%) Occasional (29-5%) HP:0001274
46 obesity 58 31 occasional (7.5%) Occasional (29-5%) HP:0001513
47 intellectual disability 58 31 occasional (7.5%) Occasional (29-5%) HP:0001249
48 nausea and vomiting 58 31 occasional (7.5%) Occasional (29-5%) HP:0002017
49 hearing impairment 58 31 very rare (1%) Occasional (29-5%) HP:0000365
50 global developmental delay 58 31 very rare (1%) Occasional (29-5%) HP:0001263

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Head:
macrocephaly
dolichocephaly

Head And Neck Eyes:
ptosis
epicanthal folds

Neurologic Behavioral Psychiatric Manifestations:
aggressive behavior
autistic features
poor communication
inappropriate chewing behavior
poor social interaction

Growth Height:
tall stature

Muscle Soft Tissue:
hypotonia, neonatal

Abdomen Gastrointestinal:
feeding difficulties, neonatal

Skin Nails Hair Skin:
tendency to overheat
lack of perspiration

Neurologic Peripheral Nervous System:
increased tolerance to pain
hyporeflexia, neonatal
abnormal reflexes

Neurologic Central Nervous System:
seizures
global developmental delay
generalized hypotonia
delayed motor development
mental retardation, moderate to severe
more
Head And Neck Ears:
hearing impairment
dysplastic ears
prominent ears
simple ears

Head And Neck Face:
pointed chin
small chin
asymmetric face
prominent brow
maxillary prognathism, mild

Head And Neck Nose:
bulbous nasal tip
saddle nose

Growth Other:
normal to accelerated growth

Skeletal Hands:
large, fleshy hands

Skin Nails Hair Nails:
dysplastic toenails

Clinical features from OMIM:

606232

UMLS symptoms related to Phelan-Mcdermid Syndrome:


seizures, reflex, abnormal

MGI Mouse Phenotypes related to Phelan-Mcdermid Syndrome:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.93 APPL2 CLN3 DLG4 MECP2 MNX1 NLGN1
2 nervous system MP:0003631 9.7 CLN3 DLG4 MECP2 MNX1 NLGN1 NLGN3
3 no phenotypic analysis MP:0003012 9.17 APPL2 CLN3 MECP2 NLGN3 SHANK2 SHANK3

Drugs & Therapeutics for Phelan-Mcdermid Syndrome

Drugs for Phelan-Mcdermid Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 15)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Zinc Approved, Investigational Phase 2 7440-66-6 32051
2
Mecasermin Approved, Investigational Phase 2 68562-41-4
3
Oxytocin Approved, Vet_approved Phase 2 50-56-6 439302 53477758
4 Pharmaceutical Solutions Phase 2
5 Mitogens Phase 2
6 insulin Phase 2
7 Insulin, Globin Zinc Phase 2
8 Hypoglycemic Agents Phase 2
9 Hormone Antagonists Phase 2
10 Hormones Phase 2
11 Oxytocics Phase 2
12
Melatonin Approved, Nutraceutical, Vet_approved Phase 1 73-31-4 896
13 Antioxidants Phase 1
14 Central Nervous System Depressants Phase 1
15 Protective Agents Phase 1

Interventional clinical trials:

(show all 11)
# Name Status NCT ID Phase Drugs
1 A Double-Blind Placebo-Controlled Crossover Trial of Insulin-Like Growth Factor-1 (IGF-1) in Children and Adolescents With 22q13 Deletion Syndrome(Phelan-McDermid Syndrome) Recruiting NCT01525901 Phase 2 Insulin-Like Growth Factor-1 (IGF-1);Normal saline
2 An Open Label Trial of Growth Hormone in Children and Adolescents With Phelan-McDermid Syndrome Targeting Social Withdrawal Recruiting NCT04003207 Phase 2 Recombinant human Growth hormone
3 Piloting Treatment With Intranasal Oxytocin in Phelan-McDermid Syndrome Recruiting NCT02710084 Phase 2 Oxytocin;Saline
4 An Open-label Study to Investigate the Safety, Tolerability and Efficacy of a Single 6-hour Intravenous Infusion of AMO-01 to Treat Adolescents and Adults With Phelan-McDermid Syndrome (PMS) and Co-morbid Epilepsy Recruiting NCT03493607 Phase 2 AMO-01
5 A Pilot Treatment Study of Insulin-Like Growth Factor-1 (IGF-1) in Autism Spectrum Disorder Recruiting NCT01970345 Phase 2 IGF-1;Placebo/saline
6 A Phase One Treatment Trial of the Circadian Sleep Disturbance in Smith-Magenis Syndrome (SMS) Completed NCT00506259 Phase 1 dTR Melatonin (NIH CC PDS);Melatonin CR
7 Mitochondrial Dysfunction in Phelan-McDermid Syndrome: Explaining Clinical Variation and Providing a Path Towards Treatment Completed NCT02000167
8 A Clinical Study to Evaluate the Relative Clinical Sensitivity, Specificity, and Performance of the a Laboratory Developed Test as a Screening Test for Fetal Chromosomal Aneuploidy, Infectious and Other Diseases, and RhD Genotyping in the General Population of Pregnant Women Completed NCT02787486
9 Mapping the Phenotype in Adults With Phelan-McDermid Syndrome Recruiting NCT03426059
10 Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome Active, not recruiting NCT02461420
11 Impact of Y-chromosome Microdeletions From Infertile Men on the Chromosomal Constitution of Their Spermatozoa and Embryos. Combined IntraCytoplasmatic Sperm Injection (ICSI) and Preimplantation Genetic Screening (PGS) as Treatment Strategy. Terminated NCT02527954

Search NIH Clinical Center for Phelan-Mcdermid Syndrome

Cochrane evidence based reviews: chromosome deletion

Genetic Tests for Phelan-Mcdermid Syndrome

Genetic tests related to Phelan-Mcdermid Syndrome:

# Genetic test Affiliating Genes
1 22q13.3 Deletion Syndrome 29 SHANK3

Anatomical Context for Phelan-Mcdermid Syndrome

MalaCards organs/tissues related to Phelan-Mcdermid Syndrome:

40
Eye, Kidney, Brain, Skin, T Cells, B Cells, Testes

Publications for Phelan-Mcdermid Syndrome

Articles related to Phelan-Mcdermid Syndrome:

(show top 50) (show all 225)
# Title Authors PMID Year
1
Prevalence of SHANK3 variants in patients with different subtypes of autism spectrum disorders. 24 56 6
22892527 2013
2
Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. 24 56 6
17173049 2007
3
22q13.2q13.32 genomic regions associated with severity of speech delay, developmental delay, and physical features in Phelan-McDermid syndrome. 61 24 56
24136618 2014
4
Association between deletion size and important phenotypes expands the genomic region of interest in Phelan-McDermid syndrome (22q13 deletion syndrome). 61 24 56
21984749 2011
5
Fulminant hepatic failure requiring liver transplantation in 22q13.3 deletion syndrome. 61 24 56
20635403 2010
6
22q13.3 deletion syndrome: clinical and molecular analysis using array CGH. 61 24 56
20186804 2010
7
Array analysis and molecular studies of INI1 in an infant with deletion 22q13 (Phelan-McDermid syndrome) and atypical teratoid/rhabdoid tumor. 61 24 56
19334084 2009
8
Identification of a recurrent breakpoint within the SHANK3 gene in the 22q13.3 deletion syndrome. 61 24 56
16284256 2006
9
Disruption of the ProSAP2 gene in a t(12;22)(q24.1;q13.3) is associated with the 22q13.3 deletion syndrome. 61 24 56
11431708 2001
10
Molecular characterization of a 130-kb terminal microdeletion at 22q in a child with mild mental retardation. 61 24 56
8981954 1997
11
Fulminant autoimmune hepatitis in a girl with 22q13 deletion syndrome: a previously unreported association. 24 56
18478261 2009
12
Interstitial 22q13 deletions: genes other than SHANK3 have major effects on cognitive and language development. 24 56
18523453 2008
13
Two brothers with 22q13 deletion syndrome and features suggestive of the Clark-Baraitser syndrome. 24 56
15930901 2005
14
Telomeric 22q13 deletions resulting from rings, simple deletions, and translocations: cytogenetic, molecular, and clinical analyses of 32 new observations. 24 56
12960216 2003
15
Molecular characterisation of the 22q13 deletion syndrome supports the role of haploinsufficiency of SHANK3/PROSAP2 in the major neurological symptoms. 24 56
12920066 2003
16
FISH-mapping of a 100-kb terminal 22q13 deletion. 24 56
12073014 2002
17
Interstitial 22q13 deletions not involving SHANK3 gene: a new contiguous gene syndrome. 61 56
24700646 2014
18
SHANK3 and IGF1 restore synaptic deficits in neurons from 22q13 deletion syndrome patients. 61 56
24132240 2013
19
Prospective investigation of autism and genotype-phenotype correlations in 22q13 deletion syndrome and SHANK3 deficiency. 61 56
23758760 2013
20
Phelan-McDermid Syndrome 61 6
20301377 2005
21
Identification of 22q13 genes most likely to contribute to Phelan McDermid syndrome. 61 24
29358616 2018
22
A novel SHANK3 interstitial microdeletion in a family with intellectual disability and brain MRI abnormalities resembling Unidentified Bright Objects. 61 24
28754298 2017
23
Clinical Reasoning: A common cause for Phelan-McDermid syndrome and neurofibromatosis type 2: One ring to bind them. 61 24
29061681 2017
24
Characterizing regression in Phelan McDermid Syndrome (22q13 deletion syndrome). 61 24
28346892 2017
25
A framework to identify contributing genes in patients with Phelan-McDermid syndrome. 61 24
29263841 2017
26
Developmental phenotype in Phelan-McDermid (22q13.3 deletion) syndrome: a systematic and prospective study in 34 children. 61 24
27118998 2016
27
Autism spectrum disorder in Phelan-McDermid syndrome: initial characterization and genotype-phenotype correlations. 61 24
26306707 2015
28
Lithium as a rescue therapy for regression and catatonia features in two SHANK3 patients with autism spectrum disorder: case reports. 61 24
25947967 2015
29
Clinical and genomic evaluation of 201 patients with Phelan-McDermid syndrome. 61 24
24481935 2014
30
The emerging role of SHANK genes in neuropsychiatric disorders. 61 24
24124131 2014
31
Phelan-McDermid syndrome: a review of the literature and practice parameters for medical assessment and monitoring. 61 24
25784960 2014
32
A pilot controlled trial of insulin-like growth factor-1 in children with Phelan-McDermid syndrome. 61 24
25685306 2014
33
Cerebellar and posterior fossa malformations in patients with autism-associated chromosome 22q13 terminal deletion. 61 24
23225497 2013
34
The 22q13.3 Deletion Syndrome (Phelan-McDermid Syndrome). 61 24
22670140 2012
35
Growth in Phelan-McDermid syndrome. 61 24
21834045 2011
36
Molecular mechanisms generating and stabilizing terminal 22q13 deletions in 44 subjects with Phelan/McDermid syndrome. 61 24
21779178 2011
37
Analysis of a purported SHANK3 mutation in a boy with autism: clinical impact of rare variant research in neurodevelopmental disabilities. 6
21062623 2011
38
Behavioral and cerebellar transmission deficits in mice lacking the autism-linked gene islet brain-2. 61 24
21048139 2010
39
Mosaic 22q13 deletions: evidence for concurrent mosaic segmental isodisomy and gene conversion. 61 24
18854866 2009
40
Population analysis of large copy number variants and hotspots of human genetic disease. 56
19166990 2009
41
Neurobehavioral profile and brain imaging study of the 22q13.3 deletion syndrome in childhood. 61 24
18625665 2008
42
Contribution of SHANK3 mutations to autism spectrum disorder. 56
17999366 2007
43
22q13.3 deletion syndrome: a recognizable malformation syndrome associated with marked speech and language delay. 61 24
17926345 2007
44
Further delineation of the 22q13 deletion syndrome. 56
15770125 2005
45
22q13 deletion syndrome. 56
11391650 2001
46
Genetic evaluation of pervasive developmental disorders: the terminal 22q13 deletion syndrome may represent a recognizable phenotype. 56
10735630 2000
47
Two 22q telomere deletions serendipitously detected by FISH. 56
9832042 1998
48
The detection of subtelomeric chromosomal rearrangements in idiopathic mental retardation. 56
7719339 1995
49
Timing, rates and spectra of human germline mutation. 24
26656846 2016
50
Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: a gradient of severity in cognitive impairments. 24
25188300 2014

Variations for Phelan-Mcdermid Syndrome

ClinVar genetic disease variations for Phelan-Mcdermid Syndrome:

6 (show all 22) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 SHANK3 NM_033517.1(SHANK3):c.3679dup (p.Ala1227fs)duplication Pathogenic 208759 rs762292772 22:51159932-51159933 22:50721504-50721505
2 SHANK3 NM_033517.1(SHANK3):c.3883delG (p.Glu1295Argfs)deletion Pathogenic 50947 rs1555910212 22:51160144-51160144 22:50721716-50721716
3 SHANK3 NM_033517.1(SHANK3):c.421C>G (p.Pro141Ala)SNV Pathogenic 50949 rs397514705 22:51117094-51117094 22:50678666-50678666
4 SHANK3 NM_033517.1(SHANK3):c.4029_4030del (p.Ser1343fs)deletion Pathogenic 375586 rs1057519395 22:51160289-51160290 22:50721861-50721862
5 SHANK3 NM_033517.1(SHANK3):c.3637dup (p.His1213fs)duplication Pathogenic 397528 rs1555910162 22:51159897-51159898 22:50721469-50721470
6 SHANK3 NM_033517.1(SHANK3):c.3679del (p.Ala1227fs)deletion Pathogenic 436718 rs762292772 22:51159933-51159933 22:50721505-50721505
7 SHANK3 NM_001372044.1(SHANK3):c.3848del (p.Gly1283fs)deletion Pathogenic 625531 rs1569115756 22:51159883-51159883 22:50721455-50721455
8 SHANK3 GRCh37/hg19 22q13.33(chr22:51123491-51144365)copy number loss Pathogenic 625628 22:51123491-51144365
9 subset of 36 genes: SHANK3 GRCh37/hg19 22q13.32-13.33(chr22:48533991-51178264)copy number loss Pathogenic 625663 22:48533991-51178264
10 subset of 94 genes: SHANK3 , TCF20 GRCh37/hg19 22q13.2-13.33(chr22:42416026-51181759)copy number loss Pathogenic 625737 22:42416026-51181759
11 SHANK3 GRCh37/hg19 22q13.33(chr22:51132804-51144365)copy number loss Pathogenic 625772 22:51132804-51144365
12 SHANK3 NM_001372044.1(SHANK3):c.4978G>T (p.Glu1660Ter)SNV Pathogenic 800506 22:51169297-51169297 22:50730869-50730869
13 SHANK3 NM_033517.1(SHANK3):c.3424_3425del (p.Leu1142fs)deletion Pathogenic/Likely pathogenic 372707 rs1555910143 22:51159685-51159686 22:50721257-50721258
14 SHANK3 NM_033517.1(SHANK3):c.2265+1G>ASNV Pathogenic/Likely pathogenic 546923 rs1396379503 22:51153476-51153476 22:50715048-50715048
15 SHANK3 NM_001372044.1(SHANK3):c.494+2T>GSNV Likely pathogenic 803709 22:51113681-51113681 22:50675253-50675253
16 SHANK3 NM_033517.1(SHANK3):c.1030G>T (p.Val344Leu)SNV Likely pathogenic 375622 rs1057519406 22:51123079-51123079 22:50684651-50684651
17 SHANK3 NM_033517.1(SHANK3):c.3627C>T (p.Leu1209=)SNV Uncertain significance 522460 rs753765611 22:51159888-51159888 22:50721460-50721460
18 SHANK3 NM_033517.1(SHANK3):c.2908G>T (p.Ala970Ser)SNV Uncertain significance 252769 rs530255181 22:51159169-51159169 22:50720741-50720741
19 SHANK3 NM_033517.1(SHANK3):c.1010C>G (p.Thr337Ser)SNV Uncertain significance 224161 rs869312715 22:51123059-51123059 22:50684631-50684631
20 SHANK3 NM_033517.1(SHANK3):c.317A>C (p.Gln106Pro)SNV Uncertain significance 203379 rs1555905307 22:51115099-51115099 22:50676671-50676671
21 SHANK3 NM_033517.1(SHANK3):c.815A>G (p.Tyr272Cys)SNV Uncertain significance 203380 rs1555905749 22:51117786-51117786 22:50679358-50679358
22 SHANK3 NM_033517.1(SHANK3):c.1305-532dupduplication Likely benign 50948 rs745950788 22:51135697-51135698 22:50697269-50697270

UniProtKB/Swiss-Prot genetic disease variations for Phelan-Mcdermid Syndrome:

73
# Symbol AA change Variation ID SNP ID
1 SHANK3 p.Pro141Ala VAR_070259 rs397514705
2 SHANK3 p.Ala1452Ser VAR_070270

Copy number variations for Phelan-Mcdermid Syndrome from CNVD:

7
# CNVD ID Chromosome Start End Type Gene Symbol CNVD Disease
1 164258 22 35900000 49691432 Copy number SHANK3 Phelan-Mcdermid syndrome
2 164259 22 35900000 49691432 Deletion Phelan-Mcdermid syndrome
3 164260 22 35900000 49691432 Deletion Phelan-Mcdermid syndrome
4 165187 22 42600000 49691432 Deletion ProSAP2 Phelan-Mcdermid syndrome
5 165188 11 69991608 70420323 Deletion SHANK Phelan-Mcdermid syndrome

Expression for Phelan-Mcdermid Syndrome

Search GEO for disease gene expression data for Phelan-Mcdermid Syndrome.

Pathways for Phelan-Mcdermid Syndrome

Pathways related to Phelan-Mcdermid Syndrome according to KEGG:

36
# Name Kegg Source Accession
1 Glutamatergic synapse hsa04724

GO Terms for Phelan-Mcdermid Syndrome

Cellular components related to Phelan-Mcdermid Syndrome according to GeneCards Suite gene sharing:

(show all 17)
# Name GO ID Score Top Affiliating Genes
1 cell junction GO:0030054 10.06 SHANK3 SHANK2 SHANK1 NRXN1 NLGN4X NLGN3
2 synapse GO:0045202 10.02 SHANK2 SHANK1 NRXN1 NLGN4X NLGN3 NLGN1
3 dendrite GO:0030425 9.97 SHANK3 SHANK2 SHANK1 NLGN4X NLGN1 DLG4
4 neuron projection GO:0043005 9.95 SHANK3 SHANK2 SHANK1 DLG4 CLN3
5 postsynaptic density GO:0014069 9.88 SHANK3 SHANK2 SHANK1 NLGN4X NLGN1 DLG4
6 glutamatergic synapse GO:0098978 9.87 SHANK1 NRXN1 NLGN1 DLG4
7 postsynaptic membrane GO:0045211 9.85 SHANK3 SHANK2 SHANK1 NLGN4X NLGN1 DLG4
8 presynapse GO:0098793 9.84 NRXN1 NLGN4X NLGN3 NLGN1
9 dendritic spine GO:0043197 9.83 SHANK3 SHANK2 SHANK1 NLGN1 DLG4
10 postsynapse GO:0098794 9.81 NLGN3 NLGN1 MECP2 DLG4
11 NMDA selective glutamate receptor complex GO:0017146 9.56 SHANK1 NLGN1
12 symmetric, GABA-ergic, inhibitory synapse GO:0098983 9.52 NLGN4X NLGN3
13 spanning component of membrane GO:0089717 9.5 NLGN4X NLGN3 NLGN1
14 ionotropic glutamate receptor complex GO:0008328 9.46 SHANK3 SHANK2 SHANK1 DLG4
15 asymmetric, glutamatergic, excitatory synapse GO:0098985 9.43 NLGN4X NLGN3 NLGN1
16 neuron spine GO:0044309 9.26 SHANK3 SHANK2 SHANK1 DLG4
17 excitatory synapse GO:0060076 9.02 SHANK1 NLGN4X NLGN3 NLGN1 DLG4

Biological processes related to Phelan-Mcdermid Syndrome according to GeneCards Suite gene sharing:

(show all 46)
# Name GO ID Score Top Affiliating Genes
1 learning GO:0007612 9.95 SHANK3 SHANK2 NRXN1 NLGN4X NLGN3 MECP2
2 long-term synaptic potentiation GO:0060291 9.93 SHANK3 SHANK2 SHANK1 NLGN3 NLGN1 MECP2
3 neuromuscular process controlling balance GO:0050885 9.91 SHANK1 NRXN1 DLG4 CLN3
4 adult behavior GO:0030534 9.91 SHANK3 SHANK2 SHANK1 NRXN1 NLGN4X NLGN3
5 synapse assembly GO:0007416 9.91 SHANK3 SHANK2 SHANK1 NRXN1 NLGN3 NLGN1
6 regulation of NMDA receptor activity GO:2000310 9.89 NRXN1 NLGN3 NLGN1 DLG4
7 neuron projection development GO:0031175 9.87 NRXN1 NLGN1 MECP2
8 memory GO:0007613 9.87 SHANK3 SHANK2 MECP2
9 modulation of chemical synaptic transmission GO:0050804 9.86 NLGN4X NLGN3 NLGN1
10 positive regulation of synapse assembly GO:0051965 9.85 NRXN1 NLGN3 NLGN1
11 positive regulation of dendritic spine development GO:0060999 9.85 SHANK3 SHANK2 SHANK1 NLGN1
12 synapse organization GO:0050808 9.84 NLGN4X NLGN3 NLGN1
13 dendritic spine morphogenesis GO:0060997 9.84 SHANK3 SHANK2 SHANK1 DLG4
14 synaptic vesicle endocytosis GO:0048488 9.83 NLGN4X NLGN3 NLGN1
15 neuron cell-cell adhesion GO:0007158 9.83 NRXN1 NLGN4X NLGN3 NLGN1
16 establishment of protein localization GO:0045184 9.82 NRXN1 NLGN1 DLG4
17 protein localization to synapse GO:0035418 9.81 SHANK1 NRXN1 NLGN1 DLG4
18 brain morphogenesis GO:0048854 9.8 SHANK3 SHANK2 SHANK1
19 presynapse assembly GO:0099054 9.8 NLGN4X NLGN3 NLGN1
20 presynaptic membrane assembly GO:0097105 9.8 NRXN1 NLGN4X NLGN3 NLGN1
21 regulation of AMPA receptor activity GO:2000311 9.8 SHANK3 SHANK2 SHANK1 NRXN1 NLGN3 NLGN1
22 receptor localization to synapse GO:0097120 9.79 NRXN1 NLGN1 DLG4
23 regulation of respiratory gaseous exchange by neurological system process GO:0002087 9.79 NLGN3 NLGN1 MECP2
24 postsynaptic membrane assembly GO:0097104 9.78 NRXN1 NLGN4X NLGN3 NLGN1
25 negative regulation of dendritic spine morphogenesis GO:0061002 9.77 UBE3A NLGN3 NLGN1
26 NMDA glutamate receptor clustering GO:0097114 9.76 SHANK3 NRXN1 NLGN1
27 synaptic growth at neuromuscular junction GO:0051124 9.75 SHANK3 SHANK2 SHANK1
28 AMPA glutamate receptor clustering GO:0097113 9.74 SHANK3 NLGN1 DLG4
29 postsynaptic density assembly GO:0097107 9.73 SHANK3 SHANK2 SHANK1
30 positive regulation of synaptic transmission, glutamatergic GO:0051968 9.73 SHANK3 SHANK2 SHANK1 NRXN1 NLGN3 NLGN1
31 regulation of dendritic spine morphogenesis GO:0061001 9.7 SHANK3 NLGN3
32 positive regulation of excitatory postsynaptic potential GO:2000463 9.7 SHANK3 SHANK2 SHANK1 NRXN1 NLGN3 NLGN1
33 regulation of long-term synaptic potentiation GO:1900271 9.69 SHANK3 NLGN3
34 negative regulation of excitatory postsynaptic potential GO:0090394 9.68 NLGN4X NLGN3
35 synaptic vesicle clustering GO:0097091 9.68 NRXN1 NLGN1
36 positive regulation of AMPA receptor activity GO:2000969 9.68 SHANK3 NLGN3
37 vocal learning GO:0042297 9.67 SHANK3 NRXN1
38 neuronal signal transduction GO:0023041 9.67 NRXN1 NLGN1
39 postsynaptic density protein 95 clustering GO:0097119 9.67 NRXN1 NLGN1
40 regulation of grooming behavior GO:2000821 9.66 NRXN1 DLG4
41 positive regulation of synaptic vesicle clustering GO:2000809 9.65 NLGN3 NLGN1
42 negative regulation of actin filament bundle assembly GO:0032232 9.64 SHANK3 SHANK1
43 positive regulation of presynaptic active zone assembly GO:1905520 9.64 NRXN1 NLGN1
44 guanylate kinase-associated protein clustering GO:0097117 9.63 SHANK3 NRXN1
45 vocalization behavior GO:0071625 9.5 SHANK3 SHANK2 SHANK1 NRXN1 NLGN4X NLGN3
46 social behavior GO:0035176 9.23 SHANK3 SHANK2 SHANK1 NRXN1 NLGN4X NLGN3

Molecular functions related to Phelan-Mcdermid Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 signaling receptor activity GO:0038023 9.73 NRXN1 NLGN4X NLGN3 NLGN1
2 SH3 domain binding GO:0017124 9.65 SHANK3 SHANK2 SHANK1
3 cell adhesion molecule binding GO:0050839 9.56 NRXN1 NLGN4X NLGN3 NLGN1
4 receptor signaling complex scaffold activity GO:0030159 9.54 SHANK3 SHANK2 SHANK1
5 neurexin family protein binding GO:0042043 9.5 NLGN4X NLGN3 NLGN1
6 acetylcholine receptor binding GO:0033130 9.46 NRXN1 DLG4
7 ionotropic glutamate receptor binding GO:0035255 9.46 SHANK3 SHANK2 SHANK1 DLG4
8 neuroligin family protein binding GO:0097109 9.4 NRXN1 DLG4
9 GKAP/Homer scaffold activity GO:0030160 9.13 SHANK3 SHANK2 SHANK1
10 scaffold protein binding GO:0097110 9.1 SHANK3 SHANK1 NLGN4X NLGN3 NLGN1 DLG4

Sources for Phelan-Mcdermid Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
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43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
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50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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