7q11.23 Copy Number Variation

Description

7q11.23 copy number variation syndrome (MIM#609757, also called Williams-Beuren region duplication syndrome, WBS duplication syndrome, Chromosome 7q11.23 duplication syndrome, or Somerville-van-der-Aa syndrome) is a duplication syndrome. The breakpoints are defined from Mervis et al., 2015.

Genomic location

Assembly:

Coordinates:

Disorder Information from Orphanet

ORPHA:96121 Microduplication syndrome

OMIM: 609757

Prevalence: 1-9 / 100 000

Definition:

7q11.23 microduplication syndrome is a rare chromosomal anomaly syndrome resulting from the partial duplication of the long arm of chromosome 7 characterized by a highly variable phenotype that typically manifests with mild to moderate intellectual disability (patients could be in the normal range), speech disorders (particularly of expressive language), and distinctive craniofacial features (brachycephaly, broad forehead, straight eyebows, broad nasal tip, short philtrum, thin upper lip and facial asymmetry). Hypotonia, developmental coordination disorders, behavioral problems (such as anxiety, ADHD and oppositional disorders) and various congenital anomalies, such as heart defects, diaphragmatic hernia, renal malformations and cryptorchidism, are frequently presented. Neurological abnormalities (visible on MRI) have been reported.

Phenotypic features:

Obligate (100%)	Very frequent (99–80%)	Frequent (79–30%)	Occasional (29–5%)	Very rare (<4-1%)	Excluded (0%)
-	Delayed speech and language development	Posteriorly rotated ears Aortic aneurysm High palate Thin upper lip vermilion Brachycephaly Macrocephaly Dolichocephaly Retrognathia Short philtrum Broad forehead Micrognathia Abnormality of earlobe Broad nasal tip Deeply set eye Long eyelashes Dental malocclusion Diastema Anxiety Hyperactivity Congenital diaphragmatic hernia Single transverse palmar crease Intellectual disability, mild Motor delay Generalized hypotonia Dysmetria Cerebellar hypoplasia Craniosynostosis Abnormal facial shape Morphological central nervous system abnormality Ventriculomegaly Unsteady gait Intellectual disability, moderate Simplified gyral pattern Abnormal columella morphology Chronic constipation	Reduced social responsiveness Inguinal hernia Cryptorchidism Short lingual frenulum Thin vermilion border Hypertelorism High forehead Chronic otitis media Overfolded helix Esotropia Aggressive behavior Abnormal repetitive mannerisms Autism with high cognitive abilities Cutis marmorata Seizure Joint hypermobility Growth delay Obesity Patent ductus arteriosus Mutism Drooling Sleep abnormality Polyphagia Short stature Sparse anterior scalp hair Large earlobe Impaired visuospatial constructive cognition Intellectual disability, severe Horizontal eyebrow Asymmetric crying face	Hypospadias Unilateral renal agenesis Hydronephrosis Hydrocephalus Round face Hearing impairment Short neck Astigmatism Strabismus Exotropia Pectus excavatum Enuresis Cafe-au-lait spot Sacral dimple Ventricular septal defect Atrial septal defect Aortic valve stenosis Pes planus Tracheomalacia Hemivertebrae Cubitus valgus Impaired smooth pursuit Aplasia/Hypoplasia of the fallopian tube Aplasia/hypoplasia of the uterus Abnormality of the optic disc Collectionism Narrow palpebral fissure Self-injurious behavior Long fingers	-

ORPHA:904 Deletion syndrome

OMIM: 194050

Prevalence: Unknown

Definition:

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.

Phenotypic features:

Obligate (100%)	Very frequent (99–80%)	Frequent (79–30%)	Occasional (29–5%)	Very rare (<4-1%)	Excluded (0%)
-	Wide mouth Macroglossia Thick lower lip vermilion Everted lower lip vermilion Narrow face Coarse facial features Epicanthus Pointed chin Broad forehead Long philtrum Micrognathia High forehead Macrotia Protruding ear Wide nasal bridge Abnormality of the neck Blepharophimosis Depression Anxiety Intellectual disability Ataxia Gait disturbance Dysmetria Tremor Hyperreflexia Failure to thrive in infancy Abnormality of the voice Hoarse voice Abnormality of the cardiovascular system Abdominal pain Abnormality of extrapyramidal motor function Gait imbalance Abnormality of speech or vocalization Phonophobia Abnormality of pelvic girdle bone morphology Hypercalcemia Short nose Involuntary movements Short stature Elfin facies High hypermetropia Dysgraphia Hyperacusis Open bite Abnormal social behavior Abnormal nervous system morphology Overfriendliness Periorbital edema Posteriorly rotated ears	Abnormality of the bladder Inguinal hernia Renal insufficiency Proteinuria Pelvic kidney Microcephaly Chronic otitis media Sensorineural hearing impairment Strabismus Visual impairment Hypodontia Abnormality of dental enamel Dental malocclusion Microdontia Autism Compulsive behaviors Hypertension Sacral dimple Abnormal fingernail morphology Hypotonia Spasticity Stroke Nystagmus-induced head nodding Joint stiffness Obesity Redundant skin Mitral valve prolapse Pulmonic stenosis Mitral regurgitation Pes planus Hypoplastic toenails Hallux valgus Nausea and vomiting Constipation Hypercalciuria Colonic diverticula Cerebral ischemia Kyphosis Arthralgia Genu valgum Elevated circulating creatine kinase concentration Hyperlordosis Clinodactyly of the 5th finger Supravalvular aortic stenosis Peripheral pulmonary artery stenosis Abnormal dental morphology Attention deficit hyperactivity disorder Hypoplasia of the zygomatic bone Arterial stenosis Abnormality of the cerebral vasculature Insomnia Renovascular hypertension Down-sloping shoulders	Recurrent urinary tract infections Bladder diverticulum Functional abnormality of male internal genitalia Cryptorchidism Hypogonadotropic hypogonadism Renal duplication Vesicoureteral reflux Renal hypoplasia Nephrocalcinosis Polycystic ovaries Gingival overgrowth Megalocornea Glaucoma Cataract Myopia Posterior embryotoxon Lacrimation abnormality Blue irides Carious teeth Pectus excavatum Nephrolithiasis Hypothyroidism Precocious puberty Osteopenia Osteoporosis Nevus flammeus Cholelithiasis Retinal arteriolar tortuosity Adducted thumb Dysarthria Umbilical hernia Dysphonia Ventricular septal defect Atrial septal defect Congestive heart failure Tetralogy of Fallot Hypertrophic cardiomyopathy Cardiomegaly Patent ductus arteriosus Sudden cardiac death Bicuspid aortic valve Myocardial infarction Abnormal cardiac septum morphology Tubulointerstitial abnormality Gastroesophageal reflux Malabsorption Rectal prolapse Cerebral cortical atrophy Recurrent respiratory infections Chiari malformation Developmental regression Tracheoesophageal fistula Overriding aorta Scoliosis Delayed skeletal maturation Radioulnar synostosis Patellar dislocation Abnormality of the ankles Abnormal circulating lipid concentration Myopathy Spina bifida occulta Abnormal form of the vertebral bodies Vertebral segmentation defect Abnormality of the gastric mucosa Abnormality of the endocardium Peptic ulcer Dilatation of the aortic arch Abnormality of the carotid arteries Multiple renal cysts Type II diabetes mellitus Atrophy/Degeneration involving the corticospinal tracts Abnormal dermatoglyphics Prematurely aged appearance Flat cornea Corneal opacity Aplasia/Hypoplasia of the iris Urethral stenosis Hypoplasia of penis Abnormality of the diencephalon Increased nuchal translucency Increased bone mineral density Synostosis of joints Death in early adulthood Joint hypermobility	-	-

Molecular pathway

View on WikiPathways

Gene Information

HGNC	Gene Name	NCBI	Ensembl	UniProt
FKBP6	FKBP prolyl isomerase family member 6 (inactive)	8468	ENSG00000077800	O75344
FZD9	frizzled class receptor 9	8326	ENSG00000188763	O00144
BAZ1B	bromodomain adjacent to zinc finger domain 1B	9031	ENSG00000009954	Q9UIG0
BCL7B	BAF chromatin remodeling complex subunit BCL7B	9275	ENSG00000106635	Q9BQE9
TBL2	transducin beta like 2	26608	ENSG00000106638	Q9Y4P3
MLXIPL	MLX interacting protein like	51085	ENSG00000009950	Q9NP71
VPS37D	VPS37D subunit of ESCRT-I	155382	ENSG00000176428	Q86XT2
DNAJC30	DnaJ heat shock protein family (Hsp40) member C30	84277	ENSG00000176410	Q96LL9
BUD23	BUD23 rRNA methyltransferase and ribosome maturation factor	114049	ENSG00000071462	O43709
STX1A	syntaxin 1A	6804	ENSG00000106089	Q16623
ABHD11	abhydrolase domain containing 11	83451	ENSG00000106077	Q8NFV4
CLDN3	claudin 3	1365	ENSG00000165215	O15551
CLDN4	claudin 4	1364	ENSG00000189143	O14493
METTL27	methyltransferase like 27	155368	ENSG00000165171	Q8N6F8
TMEM270	transmembrane protein 270	135886	ENSG00000175877	Q6UE05
ELN	elastin	2006	ENSG00000049540	P15502
LIMK1	LIM domain kinase 1	3984	ENSG00000106683	P53667
EIF4H	eukaryotic translation initiation factor 4H	7458	ENSG00000106682	Q15056
LAT2	linker for activation of T cells family member 2	7462	ENSG00000086730	Q9GZY6
RFC2	replication factor C subunit 2	5982	ENSG00000049541	P35250
CLIP2	CAP-Gly domain containing linker protein 2	7461	ENSG00000106665	Q9UDT6
GTF2IRD1	GTF2I repeat domain containing 1	9569	ENSG00000006704	Q9UHL9
GTF2I	general transcription factor IIi	2969	ENSG00000263001	P78347

Evidence

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