MCID: PHL006
MIFTS: 51

Phelan-Mcdermid Syndrome

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

Aliases & Classifications for Phelan-Mcdermid Syndrome

MalaCards integrated aliases for Phelan-Mcdermid Syndrome:

Name: Phelan-Mcdermid Syndrome 54 23 50 24 25 56 71 13
22q13.3 Deletion Syndrome 23 50 25 29 69
Chromosome 22q13.3 Deletion Syndrome 23 50 24 71
Monosomy 22q13 50 25 56
Telomeric 22q13 Monosomy Syndrome 71 69
Deletion 22q13.3 Syndrome 50 25
Deletion 22q13 Syndrome 23 25
Chromosome Deletion 42 69
22q13 Deletion Syndrome 25
22q13 Deletion 56
Phmds 71

Characteristics:

Orphanet epidemiological data:

56
monosomy 22q13
Inheritance: Not applicable; Age of onset: Infancy,Neonatal;

OMIM:

54
Inheritance:
autosomal dominant

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


HPO:

32
phelan-mcdermid syndrome:
Inheritance sporadic


GeneReviews:

23
Penetrance As expected, features of phelan-mcdermid syndrome are apparent in all individuals with non-mosaic deletion 22q13.3...

Classifications:



Summaries for Phelan-Mcdermid Syndrome

NIH Rare Diseases : 50 22q13.3 deletionsyndrome, also known as phelan-mcdermid syndrome, is a chromosome abnormality 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) at a location designated as q13.3. the signs and symptoms of this condition vary widely from person to person. common symptoms include low muscle tone (hypotonia), intellectual disability, delayed or absent speech, abnormal growth, tendency to overheat, large hands, and abnormal toenails. affected individuals may have characteristic behaviors, such as mouthing or chewing on non-food items, decreased perception of pain, and autistic-like behaviors. the loss of a particular gene on chromosome 22, called the shank3 gene, is likely responsible for many of the signs and symptoms of 22q13.3 deletion syndrome. additional genes within the deleted region probably contribute to the variable features of the syndrome. last updated: 12/6/2011

MalaCards based summary : Phelan-Mcdermid Syndrome, also known as 22q13.3 deletion syndrome, is related to chromosomal deletion syndrome and y chromosome infertility, and has symptoms including long eyelashes, strabismus and bulbous nose. An important gene associated with Phelan-Mcdermid Syndrome is SHANK3 (SH3 And Multiple Ankyrin Repeat Domains 3). The drugs Zinc and Oxytocin have been mentioned in the context of this disorder. Affiliated tissues include eye, kidney and skin, and related phenotype is no phenotypic analysis.

UniProtKB/Swiss-Prot : 71 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.

Genetics Home Reference : 25 22q13.3 deletion syndrome, which is also commonly 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.

OMIM : 54
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)

Wikipedia : 72 22q13 deletion syndrome (spoken as twenty-two q one three, see Locus (genetics)) is a genetic disorder... 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 all 49)
id Related Disease Score Top Affiliating Genes
1 chromosomal deletion syndrome 12.1
2 y chromosome infertility 11.0
3 smith-magenis syndrome 10.9
4 trichorhinophalangeal syndrome, type ii 10.6
5 wagr syndrome 10.6
6 chromosome 9p deletion syndrome 10.6
7 hypoparathyroidism-deafness-renal disease syndrome 10.6
8 ichthyosis, x-linked 10.6
9 chromosome 1p36 deletion syndrome 10.6
10 cri-du-chat syndrome 10.6
11 macrocytic anemia, refractory, due to 5q deletion, somatic 10.6
12 autism spectrum disorder 10.4
13 severe congenital neutropenia 10.2 DAZ1 USP9Y
14 chromosomal disease 10.1
15 hypogonadism 10.1
16 atypical teratoid rhabdoid tumor 10.1
17 bipolar disorder 10.1
18 neuronitis 10.1
19 retinitis pigmentosa, y-linked 10.1 DAZ1 USP9Y
20 infertility 9.9
21 congenital tracheal stenosis 9.8
22 tracheal stenosis 9.8
23 hepatitis 9.8
24 passos-bueno syndrome 9.8 DAZ1 RBMY1A1 USP9Y
25 male infertility 9.8
26 metachromatic leukodystrophy 9.8
27 aniridia 9.7
28 williams-beuren syndrome 9.6
29 jacobsen syndrome 9.6
30 norrie disease 9.6
31 choroideremia 9.6
32 wolf-hirschhorn syndrome 9.6
33 10q22.3q23 microdeletion syndrome 9.6 AZF1 DAZ1 DAZL USP9Y
34 retinitis pigmentosa 9.5
35 microphthalmia 9.5
36 prostatitis 9.5
37 ichthyosis 9.5
38 schizophrenia 9.5
39 prostate cancer 9.5
40 retinitis 9.5
41 chronic granulomatous disease 9.5
42 avoidant personality disorder 9.5 DAZ1 DAZL RBMY1A1
43 velocardiofacial syndrome 9.4
44 obesity 9.4
45 aortic valve prolapse 9.4 DAZ1 DAZL USP9Y
46 adult brain stem glioma 9.3 DAZ1 DAZL RBMY1A1 USP9Y
47 mannosidosis 9.2 DAZ1 DAZL RBMY1A1 USP9Y
48 orbital cyst 9.0 AZF1 DAZ1 DAZL RBMY1A1 USP9Y
49 nephronophthisis-like nephropathy 1 5.8 APPL2 AZF1 CLN3 DAZ1 DAZL MNX1

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



Diseases related to Phelan-Mcdermid Syndrome

Symptoms & Phenotypes for Phelan-Mcdermid Syndrome

Symptoms via clinical synopsis from OMIM:

54

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

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

Muscle Soft Tissue:
hypotonia, neonatal

Head And Neck- Nose:
bulbous nasal tip
saddle nose

Growth- Other:
normal to accelerated growth

Skeletal- Hands:
large, fleshy hands

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

Head And Neck- Eyes:
ptosis
epicanthal folds

Head And Neck- Head:
macrocephaly
dolichocephaly

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

Growth- Height:
tall stature

Skin Nails & Hair- Nails:
dysplastic toenails

Abdomen- Gastroin testinal:
feeding difficulties, neonatal

Skin Nails & Hair- Skin:
tendency to overheat
lack of perspiration


Clinical features from OMIM:

606232

Human phenotypes related to Phelan-Mcdermid Syndrome:

56 32 (show top 50) (show all 84)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 long eyelashes 56 32 frequent (33%) Frequent (79-30%) HP:0000527
2 strabismus 56 32 frequent (33%) Occasional (29-5%) HP:0000486
3 bulbous nose 56 32 frequent (33%) Frequent (79-30%) HP:0000414
4 umbilical hernia 56 32 occasional (7.5%) Occasional (29-5%) HP:0001537
5 seizures 56 32 frequent (33%) Occasional (29-5%) HP:0001250
6 ptosis 56 32 frequent (33%) Frequent (79-30%) HP:0000508
7 global developmental delay 56 32 very rare (1%) Occasional (29-5%) HP:0001263
8 hydronephrosis 56 32 occasional (7.5%) Occasional (29-5%) HP:0000126
9 hypoplastic toenails 56 32 frequent (33%) Very frequent (99-80%) HP:0001800
10 neonatal hypotonia 56 32 hallmark (90%) Very frequent (99-80%) HP:0001319
11 gastroesophageal reflux 56 32 frequent (33%) Occasional (29-5%) HP:0002020
12 macrocephaly 56 32 occasional (7.5%) Occasional (29-5%) HP:0000256
13 intellectual disability 56 32 occasional (7.5%) Occasional (29-5%) HP:0001249
14 immunodeficiency 56 32 frequent (33%) Frequent (79-30%) HP:0002721
15 hyperactivity 56 32 frequent (33%) Frequent (79-30%) HP:0000752
16 agenesis of corpus callosum 56 32 occasional (7.5%) Occasional (29-5%) HP:0001274
17 wide nasal bridge 56 32 frequent (33%) Frequent (79-30%) HP:0000431
18 full cheeks 56 32 frequent (33%) Frequent (79-30%) HP:0000293
19 vesicoureteral reflux 56 32 occasional (7.5%) Occasional (29-5%) HP:0000076
20 pointed chin 56 32 frequent (33%) Frequent (79-30%) HP:0000307
21 feeding difficulties 56 32 frequent (33%) Frequent (79-30%) HP:0011968
22 renal dysplasia 56 32 occasional (7.5%) Occasional (29-5%) HP:0000110
23 hypermetropia 56 32 occasional (7.5%) Occasional (29-5%) HP:0000540
24 recurrent skin infections 56 32 occasional (7.5%) Occasional (29-5%) HP:0001581
25 obesity 56 32 occasional (7.5%) Occasional (29-5%) HP:0001513
26 dolichocephaly 56 32 frequent (33%) Frequent (79-30%) HP:0000268
27 epicanthus 56 32 frequent (33%) Occasional (29-5%) HP:0000286
28 dental malocclusion 56 32 frequent (33%) Occasional (29-5%) HP:0000689
29 hypohidrosis 56 32 frequent (33%) Frequent (79-30%) HP:0000966
30 malar flattening 56 32 frequent (33%) Frequent (79-30%) HP:0000272
31 dental crowding 56 32 occasional (7.5%) Occasional (29-5%) HP:0000678
32 sacral dimple 56 32 frequent (33%) Frequent (79-30%) HP:0000960
33 bruxism 56 32 frequent (33%) Very frequent (99-80%) HP:0003763
34 lymphedema 56 32 frequent (33%) Occasional (29-5%) HP:0001004
35 hearing impairment 56 32 very rare (1%) Occasional (29-5%) HP:0000365
36 large hands 56 32 frequent (33%) Frequent (79-30%) HP:0001176
37 autistic behavior 56 32 frequent (33%) Frequent (79-30%) HP:0000729
38 arachnoid cyst 56 32 very rare (1%) Occasional (29-5%) HP:0100702
39 delayed speech and language development 56 32 hallmark (90%) Very frequent (99-80%) HP:0000750
40 macrotia 56 32 frequent (33%) Very frequent (99-80%) HP:0000400
41 nausea and vomiting 56 32 occasional (7.5%) Occasional (29-5%) HP:0002017
42 palpebral edema 56 32 frequent (33%) Frequent (79-30%) HP:0100540
43 thick eyebrow 56 32 frequent (33%) Frequent (79-30%) HP:0000574
44 deeply set eye 56 32 frequent (33%) Frequent (79-30%) HP:0000490
45 clinodactyly of the 5th finger 56 32 frequent (33%) Occasional (29-5%) HP:0004209
46 impaired pain sensation 56 32 frequent (33%) Very frequent (99-80%) HP:0007328
47 accelerated skeletal maturation 56 32 hallmark (90%) Very frequent (99-80%) HP:0005616
48 cerebellar cortical atrophy 56 32 occasional (7.5%) Occasional (29-5%) HP:0008278
49 hair-pulling 56 32 occasional (7.5%) Occasional (29-5%) HP:0012167
50 recurrent pyelonephritis 56 32 occasional (7.5%) Occasional (29-5%) HP:0012787

UMLS symptoms related to Phelan-Mcdermid Syndrome:


reflex, abnormal, seizures

MGI Mouse Phenotypes related to Phelan-Mcdermid Syndrome:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 no phenotypic analysis MP:0003012 9.02 APPL2 CLN3 MYCN SHANK3 UBE3A

Drugs & Therapeutics for Phelan-Mcdermid Syndrome

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

(show all 8)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1
Zinc Approved Phase 2 7440-66-6 32051 23994
2
Oxytocin Approved, Vet_approved Phase 2 50-56-6 439302 53477758
3 Hypoglycemic Agents Phase 2
4 insulin Phase 2
5 Insulin, Globin Zinc Phase 2
6 Mitogens Phase 2
7 Pharmaceutical Solutions Phase 2
8 Oxytocics Phase 2

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Clinical Trial in 22q13 Deletion Syndrome(Phelan-McDermid Syndrome) Completed NCT01525901 Phase 2 Insulin-Like Growth Factor-1 (IGF-1);Normal saline
2 Piloting Treatment With Intranasal Oxytocin in Phelan-McDermid Syndrome Recruiting NCT02710084 Phase 2 Oxytocin;Saline
3 Mitochondrial Dysfunction in Phelan-McDermid Syndrome: Explaining Clinical Variation and Providing a Path Towards Treatment Completed NCT02000167
4 Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome Recruiting NCT02461420

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:

id Genetic test Affiliating Genes
1 22q13.3 Deletion Syndrome 29
2 Phelan-Mcdermid Syndrome 24 SHANK3

Anatomical Context for Phelan-Mcdermid Syndrome

MalaCards organs/tissues related to Phelan-Mcdermid Syndrome:

39
Eye, Kidney, Skin, Tongue, Testes

Publications for Phelan-Mcdermid Syndrome

Articles related to Phelan-Mcdermid Syndrome:

(show all 39)
id Title Authors Year
1
Sleep Disturbances in Individuals With Phelan-McDermid Syndrome: Correlation With Caregivers' Sleep Quality and Daytime Functioning. ( 28364490 )
2017
2
Phelan-McDermid Syndrome. ( 28320496 )
2017
3
Homer1b/c clustering is impaired in Phelan-McDermid Syndrome iPSCs derived neurons. ( 28428614 )
2017
4
Language ENvironment Analysis (LENA) in Phelan-McDermid Syndrome: Validity and Suggestions for Use in Minimally Verbal Children with Autism Spectrum Disorder. ( 28255759 )
2017
5
Characterizing regression in Phelan McDermid Syndrome (22q13 deletion syndrome). ( 28346892 )
2017
6
Neuropsychological phenotype and psychopathology in seven adult patients with Phelan-McDermid syndrome: implications for treatment strategy. ( 26824576 )
2016
7
Is there an effect of intranasal insulin on development and behaviour in Phelan-McDermid syndrome? A randomized, double-blind, placebo-controlled trial. ( 27577546 )
2016
8
Sleep Disturbances in Individuals with Phelan-McDermid Syndrome: Correlation with Caregivers' Sleep Quality and Daytime Functioning. ( 27923425 )
2016
9
Neural selectivity for communicative auditory signals in Phelan-McDermid syndrome. ( 26909118 )
2016
10
Mitochondrial Dysfunction may explain symptom variation in Phelan-McDermid Syndrome. ( 26822410 )
2016
11
Clinical and genomic evaluation of a Chinese patient with a novel deletion associated with Phelan-McDermid syndrome. ( 27741506 )
2016
12
Phelan-McDermid syndrome presenting with developmental delays and facial dysmorphisms. ( 28018439 )
2016
13
Touchscreen learning deficits and normal social approach behavior in the Shank3B model of Phelan-McDermid Syndrome and autism. ( 27189882 )
2016
14
Brief Report: Sensory Reactivity in Children with Phelan-McDermid Syndrome. ( 26914612 )
2016
15
Characterization of the Statistical Signatures of Micro-Movements Underlying Natural Gait Patterns in Children with Phelan McDermid Syndrome: Towards Precision-Phenotyping of Behavior in ASD. ( 27445720 )
2016
16
A 9-year-old-girl with Phelan McDermid Syndrome, who had been diagnosed with an autism spectrum disorder. ( 28289594 )
2016
17
Justice in Selecting Participants for a Study in Phelan-McDermid Syndrome. ( 26982937 )
2016
18
Erratum: A pilot controlled trial of insulin-like growth factor-1 in children with Phelan-McDermid syndrome. ( 26034557 )
2015
19
Phelan McDermid Syndrome: From Genetic Discoveries to Animal Models and Treatment. ( 26350728 )
2015
20
Autism spectrum disorder in Phelan-McDermid syndrome: initial characterization and genotype-phenotype correlations. ( 26306707 )
2015
21
Phelan-McDermid Syndrome and SHANK3: Implications for Treatment. ( 25894671 )
2015
22
Clinical and genomic evaluation of 201 patients with Phelan-McDermid syndrome. ( 24481935 )
2014
23
A pilot controlled trial of insulin-like growth factor-1 in children with Phelan-McDermid syndrome. ( 25685306 )
2014
24
A stepped wedge design for testing an effect of intranasal insulin on cognitive development of children with Phelan-McDermid syndrome: A comparison of different designs. ( 25411323 )
2014
25
Phelan-McDermid syndrome: a review of the literature and practice parameters for medical assessment and monitoring. ( 25784960 )
2014
26
Deletion syndrome 22q13: what the dentist should know to manage children with Phelan-McDermid syndrome effectively. ( 25241497 )
2014
27
Adult-onset psychosis and clinical genetics: a case of Phelan-McDermid syndrome. ( 24247879 )
2013
28
Phelan-McDermid syndrome: clinical report of a 70-year-old woman. ( 23166010 )
2013
29
Phelan-McDermid syndrome presenting with autistic spectrum: are we underdiagnosing chromosomal diseases in patients with autism? ( 24078047 )
2013
30
22q13.2q13.32 genomic regions associated with severity of speech delay, developmental delay, and physical features in Phelan-McDermid syndrome. ( 24136618 )
2013
31
A patient with the classic features of Phelan-McDermid syndrome and a high immunoglobulin E level caused by a cryptic interstitial 0.72-Mb deletion in the 22q13.2 region. ( 24375995 )
2013
32
Phelan-McDermid syndrome in two adult brothers: atypical bipolar disorder as its psychopathological phenotype? ( 22570549 )
2012
33
The 22q13.3 Deletion Syndrome (Phelan-McDermid Syndrome). ( 22670140 )
2012
34
Association between deletion size and important phenotypes expands the genomic region of interest in Phelan-McDermid syndrome (22q13 deletion syndrome). ( 21984749 )
2011
35
Growth in Phelan-McDermid syndrome. ( 21834045 )
2011
36
Molecular mechanisms generating and stabilizing terminal 22q13 deletions in 44 subjects with Phelan/McDermid syndrome. ( 21779178 )
2011
37
A translocation between Xq21.33 and 22q13.33 causes an intragenic SHANK3 deletion in a woman with Phelan-McDermid syndrome and hypergonadotropic hypogonadism. ( 21271662 )
2011
38
Array analysis and molecular studies of INI1 in an infant with deletion 22q13 (Phelan-McDermid syndrome) and atypical teratoid/rhabdoid tumor. ( 19334084 )
2009
39
Phelan-McDermid Syndrome ( 20301377 )
1993

Variations for Phelan-Mcdermid Syndrome

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

71
id Symbol AA change Variation ID SNP ID
1 SHANK3 p.Pro141Ala VAR_070259 rs397514705
2 SHANK3 p.Ala1452Ser VAR_070270

ClinVar genetic disease variations for Phelan-Mcdermid Syndrome:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 SHANK3 NM_033517.1(SHANK3): c.3883delG (p.Glu1295Argfs) deletion Pathogenic GRCh37 Chromosome 22, 51160144: 51160144
2 SHANK3 NM_033517.1(SHANK3): c.421C> G (p.Pro141Ala) single nucleotide variant Pathogenic rs397514705 GRCh37 Chromosome 22, 51117094: 51117094
3 SHANK3 NM_033517.1(SHANK3): c.3679dupG (p.Ala1227Glyfs) duplication Pathogenic rs797044936 GRCh37 Chromosome 22, 51159940: 51159940
4 SHANK3 NM_033517.1(SHANK3): c.4029_4030delTG (p.Ser1343Argfs) deletion Pathogenic rs1057519395 GRCh38 Chromosome 22, 50721862: 50721863
5 SHANK3 NM_033517.1(SHANK3): c.1030G> T (p.Val344Leu) single nucleotide variant Likely pathogenic rs1057519406 GRCh37 Chromosome 22, 51123079: 51123079
6 SHANK3 NM_033517.1(SHANK3): c.3679delG (p.Ala1227Profs) deletion Pathogenic GRCh38 Chromosome 22, 50721512: 50721512

Copy number variations for Phelan-Mcdermid Syndrome from CNVD:

7
id CNVD ID Chromosom 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

GO Terms for Phelan-Mcdermid Syndrome

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

id Name GO ID Score Top Affiliating Genes
1 neuromuscular process controlling balance GO:0050885 8.96 CLN3 SHANK3
2 positive regulation of translational initiation GO:0045948 8.62 DAZ1 DAZL

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

id Name GO ID Score Top Affiliating Genes
1 mRNA 3-UTR binding GO:0003730 8.65 DAZL
2 translation activator activity GO:0008494 8.62 DAZ1 DAZL

Sources for Phelan-Mcdermid Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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