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 57 12 25 20 43 58 72 36 13 15 39
22q13.3 Deletion Syndrome 12 25 20 43 29 6 70
Chromosome 22q13.3 Deletion Syndrome 57 25 20 72
Telomeric 22q13 Monosomy Syndrome 57 72 70
Deletion 22q13.3 Syndrome 20 43
Deletion 22q13 Syndrome 25 43
Chromosome Deletion 44 70
22q13.3 Deletion 20 58
Monosomy 22q13.3 20 58
Monosomy 22q13 20 43
Phmds 57 72
Monosomy 22q13 Syndrome 12
22q13 Deletion Syndrome 43
22q13 Deletion 20

Characteristics:

Orphanet epidemiological data:

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

OMIM®:

57 (Updated 20-May-2021)
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:

25
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

GARD : 20 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 alacrima, achalasia, and mental retardation syndrome and autism spectrum disorder, 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 Circadian entrainment. The drugs Lithium carbonate and Psychotropic Drugs have been mentioned in the context of this disorder. Affiliated tissues include eye, liver and myeloid, and related phenotypes are macrotia and delayed speech and language development

Disease Ontology : 12 A chromosomal deletion syndrome that 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.

MedlinePlus Genetics : 43 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® : 57 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) (Updated 20-May-2021)

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 : 72 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 : 73 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 195)
# Related Disease Score Top Affiliating Genes
1 alacrima, achalasia, and mental retardation syndrome 30.9 UBE3A SHANK3 NRXN1 NLGN3 MECP2 CLN3
2 autism spectrum disorder 30.6 UBE3A SHANK3 SHANK2 SHANK1 NRXN1 NLGN3
3 bipolar disorder 30.3 SHANK3 NRXN1 MECP2 HOMER1 DLG4
4 autism 30.2 UBE3A SHANK3 SHANK2 SHANK1 NRXN1 NLGN3
5 azoospermia 30.2 USP9Y RBMY1A1 DAZ1 AZF1
6 angelman syndrome 30.0 UBE3A SHANK2 NRXN1 NLGN3 MECP2
7 chromosomal deletion syndrome 29.8 SHANK2 SHANK1 NRXN1 MECP2
8 fragile x syndrome 29.6 UBE3A SHANK2 SHANK1 NRXN1 NLGN3 MECP2
9 male infertility 29.6 USP9Y RBMY1A1 DAZ1 AZF1
10 pervasive developmental disorder 29.4 UBE3A SHANK2 SHANK1 NRXN1 NLGN3 MECP2
11 otodental dysplasia 11.0
12 hypotonia 10.9
13 cri-du-chat syndrome 10.9
14 thrombocytopenia, paris-trousseau type 10.9
15 hypoparathyroidism, sensorineural deafness, and renal disease 10.8
16 van den bosch syndrome 10.8
17 major affective disorder 8 10.6
18 major affective disorder 9 10.6
19 agenesis of corpus callosum, cardiac, ocular, and genital syndrome 10.5
20 hereditary lymphedema i 10.5
21 seizure disorder 10.5
22 metachromatic leukodystrophy 10.4
23 leukodystrophy 10.4
24 neurofibromatosis 10.4
25 ring chromosome 10.4
26 constipation 10.3
27 ring chromosome 22 10.3
28 partial deletion of y 10.3 USP9Y RBMY1A1 DAZ1
29 schizophrenia 15 10.2 SHANK3 SHANK2 SHANK1
30 y chromosome infertility 10.2 USP9Y RBMY1A1 DAZ1
31 chromosome 16p13.3 duplication syndrome 10.2 RABL2B RABL2A
32 spermatogenic failure, y-linked, 2 10.2 USP9Y RBMY1A1 DAZ1
33 multiple sclerosis 10.2
34 down syndrome 10.2
35 velocardiofacial syndrome 10.2
36 abnormal hair, joint laxity, and developmental delay 10.2
37 opitz-kaveggia syndrome 10.2
38 cyanosis, transient neonatal 10.2
39 polymicrogyria with or without vascular-type ehlers-danlos syndrome 10.2
40 exanthem 10.2
41 alexithymia 10.2
42 hyper ige syndrome 10.2
43 multicentric castleman disease 10.2
44 premature menopause 10.2
45 hydrocephalus 10.2
46 communicating hydrocephalus 10.2
47 epilepsy 10.2
48 hypogonadism 10.2
49 atypical teratoid rhabdoid tumor 10.2
50 cellulitis 10.2

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 89)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 macrotia 58 31 very rare (1%) Very frequent (99-80%) HP:0000400
2 delayed speech and language development 58 31 very rare (1%) 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 ptosis 58 31 frequent (33%) Frequent (79-30%) HP:0000508
10 dental malocclusion 58 31 frequent (33%) Occasional (29-5%) HP:0000689
11 wide nasal bridge 58 31 frequent (33%) Frequent (79-30%) HP:0000431
12 thick eyebrow 58 31 frequent (33%) Frequent (79-30%) HP:0000574
13 gastroesophageal reflux 58 31 frequent (33%) Occasional (29-5%) HP:0002020
14 full cheeks 58 31 frequent (33%) Frequent (79-30%) HP:0000293
15 immunodeficiency 58 31 frequent (33%) Frequent (79-30%) HP:0002721
16 strabismus 58 31 frequent (33%) Occasional (29-5%) HP:0000486
17 lymphedema 58 31 frequent (33%) Occasional (29-5%) HP:0001004
18 hypohidrosis 58 31 frequent (33%) Frequent (79-30%) HP:0000966
19 palpebral edema 58 31 frequent (33%) Frequent (79-30%) HP:0100540
20 dolichocephaly 58 31 frequent (33%) Frequent (79-30%) HP:0000268
21 clinodactyly of the 5th finger 58 31 frequent (33%) Occasional (29-5%) HP:0004209
22 deeply set eye 58 31 frequent (33%) Frequent (79-30%) HP:0000490
23 malar flattening 58 31 frequent (33%) Frequent (79-30%) HP:0000272
24 bulbous nose 58 31 very rare (1%) Frequent (79-30%) HP:0000414
25 pointed chin 58 31 very rare (1%) Frequent (79-30%) HP:0000307
26 sacral dimple 58 31 frequent (33%) Frequent (79-30%) HP:0000960
27 large hands 58 31 very rare (1%) Frequent (79-30%) HP:0001176
28 long eyelashes 58 31 frequent (33%) Frequent (79-30%) HP:0000527
29 feeding difficulties 58 31 very rare (1%) Frequent (79-30%) HP:0011968
30 autistic behavior 58 31 frequent (33%) Frequent (79-30%) HP:0000729
31 hyperactivity 58 31 frequent (33%) Frequent (79-30%) HP:0000752
32 high palate 31 frequent (33%) HP:0000218
33 autism 31 frequent (33%) HP:0000717
34 long philtrum 31 frequent (33%) HP:0000343
35 broad-based gait 31 frequent (33%) HP:0002136
36 poor eye contact 31 frequent (33%) HP:0000817
37 hyperorality 31 frequent (33%) HP:0000710
38 unsteady gait 31 frequent (33%) HP:0002317
39 2-3 toe syndactyly 31 frequent (33%) HP:0004691
40 heat intolerance 31 frequent (33%) HP:0002046
41 episodic vomiting 31 frequent (33%) HP:0002572
42 macrocephaly 58 31 very rare (1%) Occasional (29-5%) HP:0000256
43 intellectual disability 58 31 occasional (7.5%) Occasional (29-5%) HP:0001249
44 agenesis of corpus callosum 58 31 occasional (7.5%) Occasional (29-5%) HP:0001274
45 nausea and vomiting 58 31 occasional (7.5%) Occasional (29-5%) HP:0002017
46 hearing impairment 58 31 very rare (1%) Occasional (29-5%) HP:0000365
47 global developmental delay 58 31 very rare (1%) Occasional (29-5%) HP:0001263
48 umbilical hernia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001537
49 obesity 58 31 occasional (7.5%) Occasional (29-5%) HP:0001513
50 epicanthus 58 31 very rare (1%) Occasional (29-5%) HP:0000286

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Head And Neck Head:
macrocephaly
dolichocephaly

Head And Neck Eyes:
ptosis
epicanthal folds

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

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

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

Growth Height:
tall stature

Head And Neck Nose:
saddle nose
bulbous nasal tip

Growth Other:
normal to accelerated growth

Skeletal Hands:
large, fleshy hands

Skin Nails Hair Nails:
dysplastic toenails

Clinical features from OMIM®:

606232 (Updated 20-May-2021)

UMLS symptoms related to Phelan-Mcdermid Syndrome:


seizures; reflex, abnormal

MGI Mouse Phenotypes related to Phelan-Mcdermid Syndrome:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.97 APPL2 CLN3 DLG4 HOMER1 MAPK8IP2 MECP2
2 nervous system MP:0003631 9.73 CLN3 DLG4 HOMER1 MAPK8IP2 MECP2 MNX1
3 no phenotypic analysis MP:0003012 9.23 APPL2 CLN3 MAPK8IP2 MECP2 NLGN3 SHANK2

Drugs & Therapeutics for Phelan-Mcdermid Syndrome

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

(show all 46)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Lithium carbonate Approved Phase 3 554-13-2
2 Psychotropic Drugs Phase 3
3 Antidepressive Agents Phase 3
4
Oxytocin Approved, Vet_approved Phase 2 50-56-6 439302 53477758
5
Levoleucovorin Approved, Investigational Phase 2 68538-85-2 149436
6
leucovorin Approved Phase 2 58-05-9 6006
7
Mecasermin Approved, Investigational Phase 2 68562-41-4
8
Folic acid Approved, Nutraceutical, Vet_approved Phase 2 59-30-3 6037
9 Hormones Phase 2
10 Hormone Antagonists Phase 2
11 Micronutrients Phase 2
12 Trace Elements Phase 2
13 Nutrients Phase 2
14 Vitamin B Complex Phase 2
15 Folate Phase 2
16 Protective Agents Phase 2
17 Vitamins Phase 2
18 Vitamin B9 Phase 2
19 Antidotes Phase 2
20 Mitogens Phase 2
21 Pharmaceutical Solutions Phase 2
22 insulin Phase 2
23 Insulin, Globin Zinc Phase 2
24
Melatonin Approved, Nutraceutical, Vet_approved Phase 1 73-31-4 896
25 Antioxidants Phase 1
26
Hydroxocobalamin Approved 13422-51-0 11953898 15589840
27
Hydroquinone Approved, Investigational 123-31-9 785
28
Nicotinamide Approved, Investigational 98-92-0 936
29
Tocopherol Approved, Investigational 1406-66-2
30
Pantothenic acid Approved, Nutraceutical, Vet_approved 79-83-4 6613
31
Vitamin E Approved, Nutraceutical, Vet_approved 59-02-9 14985
32
Coenzyme Q10 Approved, Investigational, Nutraceutical 303-98-0 5281915
33
Cyanocobalamin Approved, Nutraceutical 68-19-9 44176380
34
Biotin Approved, Investigational, Nutraceutical 58-85-5 171548
35
Niacin Approved, Investigational, Nutraceutical 59-67-6 938
36
Cobalamin Experimental 13408-78-1 6857388
37 Tocotrienol Investigational 6829-55-6
38 Ubiquinone
39 Vitamin B3
40 Hematinics
41 Vitamin B 12
42 Tocotrienols
43 Vitamin B7
44 Nicotinic Acids
45 Vitamin B12
46 Tocopherols

Interventional clinical trials:

(show all 13)
# Name Status NCT ID Phase Drugs
1 Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency): Pilot Study. Not yet recruiting NCT04623398 Phase 3 Lithium Carbonate;Placebo
2 Piloting Treatment With Intranasal Oxytocin in Phelan-McDermid Syndrome Completed NCT02710084 Phase 2 Oxytocin;Saline
3 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 Completed NCT03493607 Phase 2 AMO-01
4 An Open Label Trial of Growth Hormone in Children and Adolescents With Phelan-McDermid Syndrome Targeting Social Withdrawal Completed NCT04003207 Phase 2 Recombinant human Growth hormone
5 The Experimental Treatment of Transfusion Dependent 5q Minus Syndrome With Leucovorin Completed NCT00004997 Phase 2 Leucovorin
6 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
7 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
8 Mapping the Phenotype in Adults With Phelan-McDermid Syndrome Completed NCT03426059
9 Mitochondrial Dysfunction in Phelan-McDermid Syndrome: Explaining Clinical Variation and Providing a Path Towards Treatment Completed NCT02000167
10 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
11 Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome Recruiting NCT02461420
12 Randomized, Placebo-controlled, Cross-over, Double-blind Study of a Metabolic Support Therapy With Q10 Ubiquinol and a Multivitamin B and E Complex in Two Cohorts of Patients With Idiopathic and Syndromic Autism (Phelan-McDermid Syndrome) Enrolling by invitation NCT04312152
13 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, Liver, Myeloid, Tongue, Brain, Cortex, Skin

Publications for Phelan-Mcdermid Syndrome

Articles related to Phelan-Mcdermid Syndrome:

(show top 50) (show all 256)
# Title Authors PMID Year
1
Prevalence of SHANK3 variants in patients with different subtypes of autism spectrum disorders. 25 6 57
22892527 2013
2
Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. 57 6 25
17173049 2007
3
22q13.2q13.32 genomic regions associated with severity of speech delay, developmental delay, and physical features in Phelan-McDermid syndrome. 25 57 61
24136618 2014
4
Association between deletion size and important phenotypes expands the genomic region of interest in Phelan-McDermid syndrome (22q13 deletion syndrome). 61 57 25
21984749 2011
5
Fulminant hepatic failure requiring liver transplantation in 22q13.3 deletion syndrome. 61 25 57
20635403 2010
6
22q13.3 deletion syndrome: clinical and molecular analysis using array CGH. 61 25 57
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 25 57
19334084 2009
8
Identification of a recurrent breakpoint within the SHANK3 gene in the 22q13.3 deletion syndrome. 25 57 61
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. 57 25 61
11431708 2001
10
Molecular characterization of a 130-kb terminal microdeletion at 22q in a child with mild mental retardation. 61 57 25
8981954 1997
11
Fulminant autoimmune hepatitis in a girl with 22q13 deletion syndrome: a previously unreported association. 57 25
18478261 2009
12
Interstitial 22q13 deletions: genes other than SHANK3 have major effects on cognitive and language development. 57 25
18523453 2008
13
Two brothers with 22q13 deletion syndrome and features suggestive of the Clark-Baraitser syndrome. 57 25
15930901 2005
14
Telomeric 22q13 deletions resulting from rings, simple deletions, and translocations: cytogenetic, molecular, and clinical analyses of 32 new observations. 25 57
12960216 2003
15
Molecular characterisation of the 22q13 deletion syndrome supports the role of haploinsufficiency of SHANK3/PROSAP2 in the major neurological symptoms. 57 25
12920066 2003
16
FISH-mapping of a 100-kb terminal 22q13 deletion. 57 25
12073014 2002
17
Interstitial 22q13 deletions not involving SHANK3 gene: a new contiguous gene syndrome. 57 61
24700646 2014
18
SHANK3 and IGF1 restore synaptic deficits in neurons from 22q13 deletion syndrome patients. 61 57
24132240 2013
19
Prospective investigation of autism and genotype-phenotype correlations in 22q13 deletion syndrome and SHANK3 deficiency. 61 57
23758760 2013
20
Identification of 22q13 genes most likely to contribute to Phelan McDermid syndrome. 25 61
29358616 2018
21
A novel SHANK3 interstitial microdeletion in a family with intellectual disability and brain MRI abnormalities resembling Unidentified Bright Objects. 61 25
28754298 2017
22
Clinical Reasoning: A common cause for Phelan-McDermid syndrome and neurofibromatosis type 2: One ring to bind them. 61 25
29061681 2017
23
Characterizing regression in Phelan McDermid Syndrome (22q13 deletion syndrome). 25 61
28346892 2017
24
A framework to identify contributing genes in patients with Phelan-McDermid syndrome. 25 61
29263841 2017
25
Developmental phenotype in Phelan-McDermid (22q13.3 deletion) syndrome: a systematic and prospective study in 34 children. 61 25
27118998 2016
26
Autism spectrum disorder in Phelan-McDermid syndrome: initial characterization and genotype-phenotype correlations. 25 61
26306707 2015
27
Lithium as a rescue therapy for regression and catatonia features in two SHANK3 patients with autism spectrum disorder: case reports. 61 25
25947967 2015
28
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. 6
25741868 2015
29
Clinical and genomic evaluation of 201 patients with Phelan-McDermid syndrome. 61 25
24481935 2014
30
The emerging role of SHANK genes in neuropsychiatric disorders. 61 25
24124131 2014
31
A pilot controlled trial of insulin-like growth factor-1 in children with Phelan-McDermid syndrome. 25 61
25685306 2014
32
Phelan-McDermid syndrome: a review of the literature and practice parameters for medical assessment and monitoring. 61 25
25784960 2014
33
Cerebellar and posterior fossa malformations in patients with autism-associated chromosome 22q13 terminal deletion. 61 25
23225497 2013
34
The 22q13.3 Deletion Syndrome (Phelan-McDermid Syndrome). 61 25
22670140 2012
35
Growth in Phelan-McDermid syndrome. 61 25
21834045 2011
36
Molecular mechanisms generating and stabilizing terminal 22q13 deletions in 44 subjects with Phelan/McDermid syndrome. 61 25
21779178 2011
37
Behavioral and cerebellar transmission deficits in mice lacking the autism-linked gene islet brain-2. 61 25
21048139 2010
38
Mosaic 22q13 deletions: evidence for concurrent mosaic segmental isodisomy and gene conversion. 61 25
18854866 2009
39
Population analysis of large copy number variants and hotspots of human genetic disease. 57
19166990 2009
40
Neurobehavioral profile and brain imaging study of the 22q13.3 deletion syndrome in childhood. 61 25
18625665 2008
41
Contribution of SHANK3 mutations to autism spectrum disorder. 57
17999366 2007
42
22q13.3 deletion syndrome: a recognizable malformation syndrome associated with marked speech and language delay. 61 25
17926345 2007
43
Further delineation of the 22q13 deletion syndrome. 57
15770125 2005
44
22q13 deletion syndrome. 57
11391650 2001
45
Genetic evaluation of pervasive developmental disorders: the terminal 22q13 deletion syndrome may represent a recognizable phenotype. 57
10735630 2000
46
Two 22q telomere deletions serendipitously detected by FISH. 57
9832042 1998
47
The detection of subtelomeric chromosomal rearrangements in idiopathic mental retardation. 57
7719339 1995
48
Timing, rates and spectra of human germline mutation. 25
26656846 2016
49
Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: a gradient of severity in cognitive impairments. 25
25188300 2014
50
Atypical teratoid rhabdoid brain tumor in an infant with ring chromosome 22. 25
25114695 2014

Variations for Phelan-Mcdermid Syndrome

ClinVar genetic disease variations for Phelan-Mcdermid Syndrome:

6 (show top 50) (show all 60)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 SHANK3 NM_033517.1(SHANK3):c.421C>G (p.Pro141Ala) SNV Pathogenic 50949 rs397514705 GRCh37: 22:51117094-51117094
GRCh38: 22:50678666-50678666
2 SHANK3 NM_033517.1(SHANK3):c.3883delG (p.Glu1295Argfs) Deletion Pathogenic 50947 rs1555910212 GRCh37: 22:51160144-51160144
GRCh38: 22:50721716-50721716
3 SHANK3 NM_033517.1(SHANK3):c.4029_4030del (p.Ser1343fs) Deletion Pathogenic 375586 rs1057519395 GRCh37: 22:51160289-51160290
GRCh38: 22:50721861-50721862
4 SHANK3 NM_001372044.1(SHANK3):c.3848del (p.Gly1283fs) Deletion Pathogenic 625531 rs1569115756 GRCh37: 22:51159883-51159883
GRCh38: 22:50721455-50721455
5 SHANK3 GRCh37/hg19 22q13.33(chr22:51123491-51144365) copy number loss Pathogenic 625628 GRCh37: 22:51123491-51144365
GRCh38:
6 overlap with 36 genes GRCh37/hg19 22q13.32-13.33(chr22:48533991-51178264) copy number loss Pathogenic 625663 GRCh37: 22:48533991-51178264
GRCh38:
7 overlap with 94 genes GRCh37/hg19 22q13.2-13.33(chr22:42416026-51181759) copy number loss Pathogenic 625737 GRCh37: 22:42416026-51181759
GRCh38:
8 SHANK3 GRCh37/hg19 22q13.33(chr22:51132804-51144365) copy number loss Pathogenic 625772 GRCh37: 22:51132804-51144365
GRCh38:
9 SHANK3 NM_033517.1(SHANK3):c.2265+1G>A SNV Pathogenic 546923 rs1396379503 GRCh37: 22:51153476-51153476
GRCh38: 22:50715048-50715048
10 SHANK3 NM_001372044.1(SHANK3):c.4978G>T (p.Glu1660Ter) SNV Pathogenic 800506 rs1603447380 GRCh37: 22:51169297-51169297
GRCh38: 22:50730869-50730869
11 overlap with 55 genes Deletion Pathogenic 976861 GRCh37:
GRCh38: 22:47823120-50759410
12 overlap with 137 genes Deletion Pathogenic 976862 GRCh37:
GRCh38: 22:43032129-50739836
13 overlap with 58 genes Deletion Pathogenic 976863 GRCh37:
GRCh38: 22:47513236-50806138
14 overlap with 69 genes Deletion Pathogenic 976864 GRCh37:
GRCh38: 22:46269281-50740560
15 overlap with 88 genes Deletion Pathogenic 976865 GRCh37:
GRCh38: 22:45708330-50737364
16 overlap with 55 genes Deletion Pathogenic 976866 GRCh37:
GRCh38: 22:47705262-50739836
17 overlap with 53 genes Deletion Pathogenic 976867 GRCh37:
GRCh38: 22:48500344-50780581
18 overlap with 59 genes Deletion Pathogenic 976868 GRCh37:
GRCh38: 22:47447433-50806138
19 overlap with 66 genes Deletion Pathogenic 976869 GRCh37:
GRCh38: 22:46489644-50806138
20 overlap with 125 genes Deletion Pathogenic 976870 GRCh37:
GRCh38: 22:43802117-50806121
21 overlap with 52 genes Deletion Pathogenic 976871 GRCh37:
GRCh38: 22:48500337-50739785
22 overlap with 85 genes Deletion Pathogenic 976872 GRCh37:
GRCh38: 22:45819932-50737806
23 overlap with 65 genes Deletion Pathogenic 976873 GRCh37:
GRCh38: 22:46467175-50759338
24 overlap with 46 genes Deletion Pathogenic 976874 GRCh37:
GRCh38: 22:49181210-50759297
25 overlap with 116 genes Deletion Pathogenic 976875 GRCh37:
GRCh38: 22:44245760-50806121
26 overlap with 111 genes Deletion Pathogenic 976876 GRCh37:
GRCh38: 22:44702479-50806138
27 SHANK3 NM_001372044.2(SHANK3):c.4290_4291del (p.Val1432fs) Deletion Pathogenic 978857 GRCh37: 22:51160326-51160327
GRCh38: 22:50721898-50721899
28 SHANK3 NM_033517.1(SHANK3):c.3679del (p.Ala1227fs) Deletion Pathogenic 436718 rs762292772 GRCh37: 22:51159933-51159933
GRCh38: 22:50721505-50721505
29 SHANK3 NM_033517.1(SHANK3):c.3637dup (p.His1213fs) Duplication Pathogenic 397528 rs1555910162 GRCh37: 22:51159897-51159898
GRCh38: 22:50721469-50721470
30 SHANK3 NM_001372044.2(SHANK3):c.3988dup (p.Arg1330fs) Duplication Pathogenic 828186 rs1603447135 GRCh37: 22:51160019-51160020
GRCh38: 22:50721591-50721592
31 SHANK3 NM_001372044.2(SHANK3):c.3777G>A (p.Glu1259=) SNV Pathogenic 973381 GRCh37: 22:51159813-51159813
GRCh38: 22:50721385-50721385
32 SHANK3 NM_001372044.2(SHANK3):c.3867dup (p.Thr1290fs) Duplication Pathogenic 975164 GRCh37: 22:51159901-51159902
GRCh38: 22:50721473-50721474
33 SHANK3 NM_001372044.2(SHANK3):c.5107C>A (p.Arg1703Ser) SNV Pathogenic 975165 GRCh37: 22:51169426-51169426
GRCh38: 22:50730998-50730998
34 SHANK3 NM_001372044.2(SHANK3):c.3857_3858insG (p.Val1287fs) Insertion Pathogenic 975877 GRCh37: 22:51159893-51159894
GRCh38: 22:50721465-50721466
35 SHANK3 NM_001372044.2(SHANK3):c.4690G>T (p.Asp1564Tyr) SNV Pathogenic 975999 GRCh37: 22:51160726-51160726
GRCh38: 22:50722298-50722298
36 SHANK3 NM_033517.1(SHANK3):c.3764_3776del (p.Arg1255fs) Deletion Pathogenic 279892 rs886041238 GRCh37: 22:51160014-51160026
GRCh38: 22:50721586-50721598
37 SHANK3 NM_001372044.2(SHANK3):c.574A>T (p.Lys192Ter) SNV Pathogenic 1029037 GRCh37: 22:51117022-51117022
GRCh38: 22:50678594-50678594
38 SHANK3 NM_033517.1(SHANK3):c.3679dup (p.Ala1227fs) Duplication Pathogenic 208759 rs762292772 GRCh37: 22:51159932-51159933
GRCh38: 22:50721504-50721505
39 SHANK3 NM_001372044.2(SHANK3):c.1871G>C (p.Arg624Pro) SNV Likely pathogenic 997006 GRCh37: 22:51142321-51142321
GRCh38: 22:50703893-50703893
40 SHANK3 NM_001372044.2(SHANK3):c.3313del (p.Leu1105fs) Deletion Likely pathogenic 988760 GRCh37: 22:51159348-51159348
GRCh38: 22:50720920-50720920
41 SHANK3 NM_001372044.1(SHANK3):c.494+2T>G SNV Likely pathogenic 803709 rs1603445997 GRCh37: 22:51113681-51113681
GRCh38: 22:50675253-50675253
42 SHANK3 NM_033517.1(SHANK3):c.3424_3425del (p.Leu1142fs) Deletion Likely pathogenic 372707 rs1555910143 GRCh37: 22:51159685-51159686
GRCh38: 22:50721257-50721258
43 SHANK3 NM_033517.1(SHANK3):c.1030G>T (p.Val344Leu) SNV Likely pathogenic 375622 rs1057519406 GRCh37: 22:51123079-51123079
GRCh38: 22:50684651-50684651
44 SHANK3 NM_033517.1(SHANK3):c.1305-532dup Duplication Uncertain significance 50948 rs745950788 GRCh37: 22:51135697-51135698
GRCh38: 22:50697269-50697270
45 SHANK3 NM_033517.1(SHANK3):c.317A>C (p.Gln106Pro) SNV Uncertain significance 203379 rs1555905307 GRCh37: 22:51115099-51115099
GRCh38: 22:50676671-50676671
46 SHANK3 NM_033517.1(SHANK3):c.815A>G (p.Tyr272Cys) SNV Uncertain significance 203380 rs1555905749 GRCh37: 22:51117786-51117786
GRCh38: 22:50679358-50679358
47 SHANK3 NM_033517.1(SHANK3):c.1010C>G (p.Thr337Ser) SNV Uncertain significance 224161 rs869312715 GRCh37: 22:51123059-51123059
GRCh38: 22:50684631-50684631
48 SHANK3 NM_001372044.2(SHANK3):c.4108GAG[1] (p.Glu1371del) Microsatellite Uncertain significance 988742 GRCh37: 22:51160144-51160146
GRCh38: 22:50721716-50721718
49 SHANK3 NM_001372044.2(SHANK3):c.2648G>C (p.Arg883Pro) SNV Uncertain significance 995856 GRCh37: 22:51158684-51158684
GRCh38: 22:50720256-50720256
50 SHANK3 NM_001372044.2(SHANK3):c.5057C>G (p.Ser1686Trp) SNV Uncertain significance 996092 GRCh37: 22:51169376-51169376
GRCh38: 22:50730948-50730948

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

72
# 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 SHANK3 Phelan-Mcdermid syndrome
5 165188 11 69991608 70420323 Deletion SHANK2 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 12)
# Name GO ID Score Top Affiliating Genes
1 cell projection GO:0042995 9.99 SHANK2 RABL2B NRXN1 HOMER1 DLG4 APPL2
2 cell junction GO:0030054 9.97 SHANK3 SHANK2 SHANK1 NRXN1 NLGN3 HOMER1
3 neuron projection GO:0043005 9.88 SHANK3 SHANK2 SHANK1 HOMER1 DLG4 CLN3
4 glutamatergic synapse GO:0098978 9.8 SHANK3 SHANK1 HOMER1 DLG4
5 postsynaptic membrane GO:0045211 9.78 SHANK3 SHANK2 SHANK1 DLG4
6 postsynapse GO:0098794 9.76 NLGN3 MECP2 HOMER1 DLG4
7 postsynaptic density GO:0014069 9.73 SHANK3 SHANK2 SHANK1 MAPK8IP2 HOMER1 DLG4
8 dendritic spine GO:0043197 9.72 SHANK3 SHANK2 SHANK1 HOMER1 DLG4
9 excitatory synapse GO:0060076 9.61 SHANK1 NLGN3 DLG4
10 synapse GO:0045202 9.61 SHANK3 SHANK2 SHANK1 NRXN1 NLGN3 MECP2
11 neuron spine GO:0044309 9.33 SHANK3 HOMER1 DLG4
12 ionotropic glutamate receptor complex GO:0008328 8.92 SHANK3 SHANK2 SHANK1 DLG4

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

(show all 35)
# Name GO ID Score Top Affiliating Genes
1 chemical synaptic transmission GO:0007268 9.98 NRXN1 NLGN3 MECP2 HOMER1 DLG4
2 synapse assembly GO:0007416 9.85 SHANK3 SHANK2 NRXN1 NLGN3 MECP2
3 long-term synaptic potentiation GO:0060291 9.83 SHANK3 SHANK2 SHANK1 MECP2
4 neuromuscular process controlling balance GO:0050885 9.83 SHANK3 SHANK1 NRXN1 DLG4 CLN3
5 adult behavior GO:0030534 9.8 SHANK3 SHANK2 SHANK1 NRXN1 NLGN3
6 dendritic spine morphogenesis GO:0060997 9.78 SHANK3 SHANK2 SHANK1 DLG4
7 regulation of NMDA receptor activity GO:2000310 9.77 NRXN1 MAPK8IP2 DLG4
8 regulation of synaptic transmission, glutamatergic GO:0051966 9.77 MAPK8IP2 HOMER1 CLN3
9 positive regulation of synaptic transmission, glutamatergic GO:0051968 9.77 SHANK3 SHANK2 SHANK1 NRXN1 NLGN3
10 positive regulation of dendritic spine development GO:0060999 9.74 SHANK3 SHANK2 SHANK1
11 brain morphogenesis GO:0048854 9.73 SHANK3 SHANK2 SHANK1
12 learning GO:0007612 9.73 SHANK3 SHANK2 NRXN1 NLGN3 MECP2 DLG4
13 behavior GO:0007610 9.72 SHANK3 SHANK2 SHANK1
14 regulation of AMPA receptor activity GO:2000311 9.72 SHANK3 SHANK2 SHANK1 NRXN1 MAPK8IP2
15 protein localization to synapse GO:0035418 9.71 SHANK1 NRXN1 DLG4
16 synaptic growth at neuromuscular junction GO:0051124 9.69 SHANK3 SHANK2 SHANK1
17 long-term synaptic depression GO:0060292 9.67 SHANK3 SHANK2
18 postsynaptic density assembly GO:0097107 9.67 SHANK3 SHANK2 SHANK1
19 neuron cell-cell adhesion GO:0007158 9.66 NRXN1 NLGN3
20 locomotory exploration behavior GO:0035641 9.66 SHANK3 DLG4
21 regulation of respiratory gaseous exchange by neurological system process GO:0002087 9.65 NLGN3 MECP2
22 receptor localization to synapse GO:0097120 9.65 NRXN1 DLG4
23 regulation of fibroblast migration GO:0010762 9.65 CLN3 APPL2
24 presynaptic membrane assembly GO:0097105 9.64 NRXN1 NLGN3
25 postsynaptic membrane assembly GO:0097104 9.64 NRXN1 NLGN3
26 positive regulation of AMPA receptor activity GO:2000969 9.63 SHANK3 NLGN3
27 vocal learning GO:0042297 9.63 SHANK3 NRXN1
28 positive regulation of excitatory postsynaptic potential GO:2000463 9.63 SHANK3 SHANK2 SHANK1 NRXN1 NLGN3 DLG4
29 regulation of grooming behavior GO:2000821 9.62 SHANK3 DLG4
30 NMDA glutamate receptor clustering GO:0097114 9.62 SHANK3 NRXN1
31 AMPA glutamate receptor clustering GO:0097113 9.61 SHANK3 DLG4
32 negative regulation of actin filament bundle assembly GO:0032232 9.61 SHANK3 SHANK1
33 guanylate kinase-associated protein clustering GO:0097117 9.58 SHANK3 NRXN1
34 vocalization behavior GO:0071625 9.43 SHANK3 SHANK2 SHANK1 NRXN1 NLGN3 DLG4
35 social behavior GO:0035176 9.23 SHANK3 SHANK2 SHANK1 NRXN1 NLGN3 MECP2

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

# Name GO ID Score Top Affiliating Genes
1 SH3 domain binding GO:0017124 9.54 SHANK3 SHANK2 SHANK1
2 scaffold protein binding GO:0097110 9.46 SHANK3 SHANK1 NLGN3 DLG4
3 acetylcholine receptor binding GO:0033130 9.32 NRXN1 DLG4
4 neuroligin family protein binding GO:0097109 9.26 NRXN1 DLG4
5 ionotropic glutamate receptor binding GO:0035255 9.26 SHANK3 SHANK2 SHANK1 DLG4
6 GKAP/Homer scaffold activity GO:0030160 8.8 SHANK3 SHANK2 SHANK1

Sources for Phelan-Mcdermid Syndrome

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