ORPHA:904

Williams syndrome

Synonyms: Deletion 7q11.23 · Monosomy 7q11.23 · Williams-Beuren syndrome

Type: Malformation syndrome
Group: Disorder
Inheritance: Autosomal dominant
Age of onset: Antenatal, Neonatal
Status: active

A rare genetic multisystemic neurodevelopmental disorder characterized by a distinct facial appearance, cardiac anomalies (most frequently supravalvular aortic stenosis), cognitive and developmental abnormalities, and connective tissue abnormalities (e.g., joint laxity). Facial dysmorphism is characterized by a broad forehead, bitemporal narrowing, periorbital fullness, stellate and/or lacy iris pattern, short upturned nose with bulbous tip, long philtrum, wide mouth, full lips and mild micrognathia.

Names in Orphadata languages

12 of 12 languages

Lang	Name	Synonyms
en	Williams syndrome	Deletion 7q11.23 · Monosomy 7q11.23 · Williams-Beuren syndrome
fr	Syndrome de Williams	Délétion 7q11.23 · Monosomie 7q11.23 · Syndrome de Williams-Beuren
de	Williams-Syndrom	Williams-Beuren-Syndrom
es	Síndrome de Williams	Deleción 7q11.23 · Monosomía 7q11.23 · Síndrome de Williams-Beuren
it	Sindrome di Williams	Delezione 7q11.23 · Monosomia 7q11.23 · Sindrome di Williams-Beuren
nl	Syndroom van Williams	Deletie 7q11.23 · Monosomie 7q11.23 · Syndroom van Williams-Beuren
pt	Síndrome Williams	Síndrome Williams-Beuren
pl	Zespół Williamsa	Delecja 7q11.23 · Monosomia 7q11.23 · Zespół Williamsa i Beurena
cs	Williamsův syndrom	Delece 7q11.23 · Monozomie 7q11.23 · Williamsův-Beurenův syndrom · Williams-Beurenův syndrom
uk	Синдром Вільямса	Делеція 7q11.23 · Моносомія 7q11.23 · Синдром Вільямса-Борена
zh	威廉斯综合征	Williams-Beuren综合征
tr	Williams sendromu	Delesyon 7q11.23 · Monozomi 7q11.23 · Williams-Beuren sendromu

Definition in:

Cross-references

qualifier = Orphanet mapping relation

Source	Code	Qualifier	ICD relation	Validation
OMIM	194050	E		validated
ICD-10	Q93.8	NTBT	attributed	validated
ICD-11	LD44.70	NTBT	index	validated
MONDO	0008678	E		validated
MeSH	D018980	E		validated
UMLS	C0175702	E		validated
GARD	7891	E		validated
MedDRA	10049644	E		validated

E exact · NTBT this ORPHAcode is narrower than the target · BTNT broader than the target · ND not decided.

Classification

Preferential parent (Orphanet linearisation):

ORPHA:93890Rare developmental defect during embryogenesis

Parents in the classifications (12):

ORPHA:183570Genetic malformation syndrome with short stature
rare genetic diseases
ORPHA:611327Genetic multiple congenital anomalies/dysmorphic syndrome-intellectual disability
rare genetic diseases
ORPHA:139021Malformation syndrome with short stature
rare developmental anomalies during embryogenesis
ORPHA:306765Motor stereotypies
rare genetic diseases; rare neurological diseases
ORPHA:102283Multiple congenital anomalies/dysmorphic syndrome-intellectual disability
rare developmental anomalies during embryogenesis; rare neurological diseases
ORPHA:262056Partial deletion of the long arm of chromosome 7 syndrome
rare developmental anomalies during embryogenesis; rare genetic diseases
ORPHA:506213Rare disorder potentially indicated for kidney transplant
rare transplant-related disorders
ORPHA:156629Rare genetic cause of hypertension
rare genetic diseases; rare renal diseases
ORPHA:98033Rare neurologic disease with psychiatric involvement
rare neurological diseases
ORPHA:156532Rare syndrome with cardiac malformations
rare developmental anomalies during embryogenesis; rare cardiac malformations; rare genetic diseases
ORPHA:139393Syndromic craniosynostosis
rare developmental anomalies during embryogenesis; rare genetic diseases; rare bone diseases
ORPHA:98574Syndromic epicanthus
rare developmental anomalies during embryogenesis; rare genetic diseases; rare ophthalmic disorders

No children.

Genes

18 direct

Gene	Association	Status	HGNC	Ensembl	OMIM	Locus	Name	Source of validation
DNAJC30	Candidate gene tested in	Not yet assessed	HGNC:16410	ENSG00000176410	618202	7q11.23	DnaJ heat shock protein family (Hsp40) member C30
RFC2	Candidate gene tested in	Assessed	HGNC:9970	ENSG00000049541	600404	7q11.23	replication factor C subunit 2	20301427[PMID]
BAZ1B	Role in the phenotype of	Assessed	HGNC:961	ENSG00000009954	605681	7q11.23	bromodomain adjacent to zinc finger domain 1B	20301427[PMID]
BUD23	Role in the phenotype of	Assessed	HGNC:16405	ENSG00000071462	615733	7q11.23	BUD23 rRNA methyltransferase and ribosome maturation factor	11978965[PMID]
CLIP2	Role in the phenotype of	Assessed	HGNC:2586	ENSG00000106665	603432	7q11.23	CAP-Gly domain containing linker protein 2	20301427[PMID]
EIF4H	Role in the phenotype of	Assessed	HGNC:12741	ENSG00000106682	603431	7q11.23	eukaryotic translation initiation factor 4H	8812460[PMID]
ELN	Role in the phenotype of	Assessed	HGNC:3327	ENSG00000049540	130160	7q11.23	elastin	20301427[PMID]
FKBP6	Role in the phenotype of	Assessed	HGNC:3722	ENSG00000077800	604839	7q11.23	FKBP prolyl isomerase family member 6 (inactive)	9782077[PMID]
GTF2I	Role in the phenotype of	Assessed	HGNC:4659	ENSG00000263001	601679	7q11.23	general transcription factor IIi	20301427[PMID]
GTF2IRD1	Role in the phenotype of	Assessed	HGNC:4661	ENSG00000006704	604318	7q11.23	GTF2I repeat domain containing 1	20301427[PMID]
GTF2IRD2	Role in the phenotype of	Assessed	HGNC:30775	ENSG00000196275	608899	7q11.23	GTF2I repeat domain containing 2	15243160[PMID]
LIMK1	Role in the phenotype of	Assessed	HGNC:6613	ENSG00000106683	601329	7q11.23	LIM domain kinase 1	20301427[PMID]
METTL27	Role in the phenotype of	Assessed	HGNC:19068	ENSG00000165171	612546	7q11.23	methyltransferase like 27	18398435[PMID]
NCF1	Role in the phenotype of	Assessed	HGNC:7660	ENSG00000158517	608512	7q11.23	neutrophil cytosolic factor 1	9311751[PMID]
STX1A	Role in the phenotype of	Assessed	HGNC:11433	ENSG00000106089	186590	7q11.23	syntaxin 1A	9311751[PMID]
TBL2	Role in the phenotype of	Assessed	HGNC:11586	ENSG00000106638	605842	7q11.23	transducin beta like 2	20301427[PMID]
TMEM270	Role in the phenotype of	Assessed	HGNC:23018	ENSG00000175877	612547	7q11.23	transmembrane protein 270	18398435[PMID]
VPS37D	Role in the phenotype of	Assessed	HGNC:18287	ENSG00000176428	610039	7q11.23	VPS37D subunit of ESCRT-I	19897463[PMID]

Prevalence and incidence

4 records

Type	Class	Value	Area	Qualification	Validation	Source
Prevalence at birth	1-5 / 10 000	13.3 / 100 000	Norway	Value and class	Validated	12088082[PMID]
Prevalence at birth	1-9 / 100 000	4.2 / 100 000	Hong Kong	Value and class	Validated	14967851[PMID]
Point prevalence	1-5 / 10 000	13.3 / 100 000	Norway	Value and class	Validated	12088082[PMID]_ORPHANET
Point prevalence	1-9 / 100 000	4.2 / 100 000	Hong Kong	Value and class	Validated	14967851[PMID]_ORPHANET

Value is Orphadata's ValMoy: the mean estimate per 100 000 for prevalence and incidence, the number of cases or families for case reports.

HPO phenotypes

186 annotations · validated 2016-06-01

HPO	Term (as annotated by Orphanet)	Diagnostic
Very frequent (99-80%)
HP:0002027	Abdominal pain
HP:0012639	Abnormal nervous system morphology
HP:0012433	Abnormal social behavior
HP:0002071	Abnormality of extrapyramidal motor function
HP:0002644	Abnormality of pelvic girdle bone morphology
HP:0002167	Abnormality of speech or vocalization
HP:0001626	Abnormality of the cardiovascular system
HP:0000464	Abnormality of the neck
HP:0001608	Abnormality of the voice
HP:0000739	Anxiety
HP:0001251	Ataxia
HP:0000581	Blepharophimosis
HP:0000337	Broad forehead
HP:0000280	Coarse facial features
HP:0000716	Depression
HP:0010526	Dysgraphia
HP:0001310	Dysmetria
HP:0004428	Elfin facies
HP:0000286	Epicanthus
HP:0000232	Everted lower lip vermilion
HP:0001531	Failure to thrive in infancy
HP:0001288	Gait disturbance
HP:0002141	Gait imbalance
HP:0000348	High forehead
HP:0008499	High hypermetropia
HP:0001609	Hoarse voice
HP:0010780	Hyperacusis
HP:0003072	Hypercalcemia
HP:0001347	Hyperreflexia
HP:0001249	Intellectual disability
HP:0004305	Involuntary movements
HP:0000343	Long philtrum
HP:0000158	Macroglossia
HP:0000400	Macrotia
HP:0000347	Micrognathia
HP:0000275	Narrow face
HP:0010807	Open bite
HP:0100025	Overfriendliness
HP:0100539	Periorbital edema
HP:0002183	Phonophobia
HP:0000307	Pointed chin
HP:0000358	Posteriorly rotated ears
HP:0000411	Protruding ear
HP:0003196	Short nose
HP:0004322	Short stature
HP:0000179	Thick lower lip vermilion
HP:0001337	Tremor
HP:0000154	Wide mouth
HP:0000431	Wide nasal bridge
Frequent (79-30%)
HP:0006482	Abnormal dental morphology
HP:0001231	Abnormal fingernail morphology
HP:0000682	Abnormality of dental enamel
HP:0000014	Abnormality of the bladder
HP:0100659	Abnormality of the cerebral vasculature
HP:0100545	Arterial stenosis
HP:0002829	Arthralgia
HP:0007018	Attention deficit hyperactivity disorder
HP:0000717	Autism
HP:0002637	Cerebral ischemia
HP:0000389	Chronic otitis media
HP:0004209	Clinodactyly of the 5th finger
HP:0002253	Colonic diverticula
HP:0000722	Compulsive behaviors
HP:0002019	Constipation
HP:0000689	Dental malocclusion
HP:0200021	Down-sloping shoulders
HP:0003236	Elevated circulating creatine kinase concentration
HP:0002857	Genu valgum
HP:0001822	Hallux valgus
HP:0002150	Hypercalciuria
HP:0003307	Hyperlordosis
HP:0000822	Hypertension
HP:0000668	Hypodontia
HP:0010669	Hypoplasia of the zygomatic bone
HP:0001800	Hypoplastic toenails
HP:0001252	Hypotonia
HP:0000023	Inguinal hernia
HP:0100785	Insomnia
HP:0001387	Joint stiffness
HP:0002808	Kyphosis
HP:0000252	Microcephaly
HP:0000691	Microdontia
HP:0001653	Mitral regurgitation
HP:0001634	Mitral valve prolapse
HP:0002017	Nausea and vomiting
HP:0001361	Nystagmus-induced head nodding
HP:0001513	Obesity
HP:0000125	Pelvic kidney
HP:0004969	Peripheral pulmonary artery stenosis
HP:0001763	Pes planus
HP:0000093	Proteinuria
HP:0001642	Pulmonic stenosis
HP:0001582	Redundant skin
HP:0000083	Renal insufficiency
HP:0100817	Renovascular hypertension
HP:0000960	Sacral dimple
HP:0000407	Sensorineural hearing impairment
HP:0001257	Spasticity
HP:0000486	Strabismus
HP:0001297	Stroke
HP:0004381	Supravalvular aortic stenosis
HP:0000505	Visual impairment
Occasional (29-5%)
HP:0001671	Abnormal cardiac septum morphology
HP:0003119	Abnormal circulating lipid concentration
HP:0007477	Abnormal dermatoglyphics
HP:0003312	Abnormal form of the vertebral bodies
HP:0003028	Abnormality of the ankles
HP:0005344	Abnormality of the carotid arteries
HP:0010662	Abnormality of the diencephalon
HP:0004306	Abnormality of the endocardium
HP:0004295	Abnormality of the gastric mucosa
HP:0001181	Adducted thumb
HP:0008053	Aplasia/Hypoplasia of the iris
HP:0001631	Atrial septal defect
HP:0007372	Atrophy/Degeneration involving the corticospinal tracts
HP:0001647	Bicuspid aortic valve
HP:0000015	Bladder diverticulum
HP:0000635	Blue irides
HP:0001640	Cardiomegaly
HP:0000670	Carious teeth
HP:0000518	Cataract
HP:0002120	Cerebral cortical atrophy
HP:0002308	Chiari malformation
HP:0001081	Cholelithiasis
HP:0001635	Congestive heart failure
HP:0007957	Corneal opacity
HP:0000028	Cryptorchidism
HP:0100613	Death in early adulthood
HP:0002750	Delayed skeletal maturation
HP:0002376	Developmental regression
HP:0005113	Dilatation of the aortic arch
HP:0001260	Dysarthria
HP:0001618	Dysphonia
HP:0007720	Flat cornea
HP:0000025	Functional abnormality of male internal genitalia
HP:0002020	Gastroesophageal reflux
HP:0000212	Gingival overgrowth
HP:0000501	Glaucoma
HP:0001639	Hypertrophic cardiomyopathy
HP:0000044	Hypogonadotropic hypogonadism
HP:0008736	Hypoplasia of penis
HP:0000821	Hypothyroidism
HP:0011001	Increased bone mineral density
HP:0010880	Increased nuchal translucency
HP:0001382	Joint hypermobility
HP:0000632	Lacrimation abnormality
HP:0002024	Malabsorption
HP:0000485	Megalocornea
HP:0005562	Multiple renal cysts
HP:0001658	Myocardial infarction
HP:0003198	Myopathy
HP:0000545	Myopia
HP:0000121	Nephrocalcinosis
HP:0000787	Nephrolithiasis
HP:0001052	Nevus flammeus
HP:0000938	Osteopenia
HP:0000939	Osteoporosis
HP:0002623	Overriding aorta
HP:0002999	Patellar dislocation
HP:0001643	Patent ductus arteriosus
HP:0000767	Pectus excavatum
HP:0004398	Peptic ulcer
HP:0000147	Polycystic ovaries
HP:0000627	Posterior embryotoxon
HP:0000826	Precocious puberty
HP:0007495	Prematurely aged appearance
HP:0002974	Radioulnar synostosis
HP:0002035	Rectal prolapse
HP:0002205	Recurrent respiratory infections
HP:0000010	Recurrent urinary tract infections
HP:0000075	Renal duplication
HP:0000089	Renal hypoplasia
HP:0001136	Retinal arteriolar tortuosity
HP:0002650	Scoliosis
HP:0003298	Spina bifida occulta
HP:0001645	Sudden cardiac death
HP:0100240	Synostosis of joints
HP:0001636	Tetralogy of Fallot
HP:0002575	Tracheoesophageal fistula
HP:0001969	Tubulointerstitial abnormality
HP:0005978	Type II diabetes mellitus
HP:0001537	Umbilical hernia
HP:0008661	Urethral stenosis
HP:0001629	Ventricular septal defect
HP:0003422	Vertebral segmentation defect
HP:0000076	Vesicoureteral reflux

Run the differential on the 12 obligate / very frequent terms

Sources for this card

Orphanet page: orpha.net/en/disease/detail/904
This record as JSON: /data/d/904.json