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Velocardiofacial syndrome(VCFS)

MedGen UID:
65085
Concept ID:
C0220704
Disease or Syndrome
Synonyms: Shprintzen syndrome; Shprintzen VCF syndrome; VCF syndome; VCF SYNDROME; VCFS
 
Genes (locations): DGCR2 (22q11.21); DGCR6 (22q11.21); DGCR8 (22q11.21); ESS2 (22q11.21); TBX1 (22q11.21)
 
Monarch Initiative: MONDO:0008644
OMIM®: 192430

Disease characteristics

Excerpted from the GeneReview: 22q11.2 Deletion Syndrome
Individuals with 22q11.2 deletion syndrome (22q11.2DS) can present with a wide range of features that are highly variable, even within families. The major clinical manifestations of 22q11.2DS include congenital heart disease, particularly conotruncal malformations (ventricular septal defect, tetralogy of Fallot, interrupted aortic arch, and truncus arteriosus), palatal abnormalities (velopharyngeal incompetence, submucosal cleft palate, bifid uvula, and cleft palate), immune deficiency, characteristic facial features, and learning difficulties. Hearing loss can be sensorineural and/or conductive. Laryngotracheoesophageal, gastrointestinal, ophthalmologic, central nervous system, skeletal, and genitourinary anomalies also occur. Psychiatric illness and autoimmune disorders are more common in individuals with 22q11.2DS. [from GeneReviews]
Authors:
Donna M McDonald-McGinn  |  Heather S Hain  |  Beverly S Emanuel, et. al.   view full author information

Additional description

From MedlinePlus Genetics
Many children with 22q11.2 deletion syndrome have developmental delays, including delayed growth and speech development, and some have mild intellectual disability or learning disabilities. Older affected individuals have difficulty reading, performing tasks involving math, and problem solving. Children with this condition often need help changing and adapting their behaviors when responding to situations. Additionally, affected children are more likely than children without 22q11.2 deletion syndrome to have attention-deficit/hyperactivity disorder (ADHD) and developmental conditions such as autism spectrum disorder that affect communication and social interaction.

22q11.2 deletion syndrome has many possible signs and symptoms that can affect almost any part of the body. The features of this syndrome vary widely, even among affected members of the same family. People with 22q11.2 deletion syndrome commonly have heart abnormalities that are often present from birth, recurrent infections caused by problems with the immune system, and distinctive facial features. In affected individuals, the muscles that form the roof of the mouth (palate) may not close completely, even though the tissue covering them does, resulting in a condition called submucosal cleft palate. The abnormal palate is often highly arched and there may be a split in the soft flap of tissue that hangs from the back of the mouth (bifid uvula). Submucosal cleft palate can also interfere with normal speech by causing air to come out of the nose during speech, leading to nasal-sounding speech. Affected individuals may also have breathing problems, kidney abnormalities, low levels of calcium in the blood (which can result in seizures), a decrease in blood platelets (thrombocytopenia), significant feeding difficulties, gastrointestinal problems, and hearing loss. Skeletal differences are possible, including mild short stature and, less frequently, abnormalities of the spinal bones.

22q11.2 deletion syndrome (which is also known by several other names, listed below) is a disorder caused by the deletion of a small piece of chromosome 22. The deletion occurs near the middle of the chromosome at a location designated q11.2.

Because the signs and symptoms of 22q11.2 deletion syndrome are so varied, different groupings of features were once described as separate conditions. Doctors named these conditions DiGeorge syndrome, velocardiofacial syndrome (also called Shprintzen syndrome), and conotruncal anomaly face syndrome. In addition, some children with the 22q11.2 deletion were diagnosed with the autosomal dominant form of Opitz G/BBB syndrome and Cayler cardiofacial syndrome. Once the genetic basis for these disorders was identified, doctors determined that they were all part of a single syndrome with many possible signs and symptoms. To avoid confusion, this condition is usually called 22q11.2 deletion syndrome, a description based on its underlying genetic cause.  https://medlineplus.gov/genetics/condition/22q112-deletion-syndrome

Clinical features

From HPO
Cryptorchidism
MedGen UID:
8192
Concept ID:
C0010417
Congenital Abnormality
Cryptorchidism, or failure of testicular descent, is a common human congenital abnormality with a multifactorial etiology that likely reflects the involvement of endocrine, environmental, and hereditary factors. Cryptorchidism can result in infertility and increases risk for testicular tumors. Testicular descent from abdomen to scrotum occurs in 2 distinct phases: the transabdominal phase and the inguinoscrotal phase (summary by Gorlov et al., 2002).
Abnormality of the hand
MedGen UID:
6715
Concept ID:
C0018564
Anatomical Abnormality
An abnormality affecting one or both hands.
Talipes
MedGen UID:
220976
Concept ID:
C1301937
Congenital Abnormality
A deformity of foot and ankle that has different subtypes that are talipes equinovarus, talipes equinovalgus, talipes calcaneovarus and talipes calcaneovalgus.
Ventricular septal defect
MedGen UID:
42366
Concept ID:
C0018818
Congenital Abnormality
A hole between the two bottom chambers (ventricles) of the heart. The defect is centered around the most superior aspect of the ventricular septum.
Tetralogy of Fallot
MedGen UID:
21498
Concept ID:
C0039685
Congenital Abnormality
People with CCHD have one or more specific heart defects. The heart defects classified as CCHD include coarctation of the aorta, double-outlet right ventricle, D-transposition of the great arteries, Ebstein anomaly, hypoplastic left heart syndrome, interrupted aortic arch, pulmonary atresia with intact septum, single ventricle, total anomalous pulmonary venous connection, tetralogy of Fallot, tricuspid atresia, and truncus arteriosus.\n\nEach of the heart defects associated with CCHD affects the flow of blood into, out of, or through the heart. Some of the heart defects involve structures within the heart itself, such as the two lower chambers of the heart (the ventricles) or the valves that control blood flow through the heart. Others affect the structure of the large blood vessels leading into and out of the heart (including the aorta and pulmonary artery). Still others involve a combination of these structural abnormalities.\n\nSome people with treated CCHD have few related health problems later in life. However, long-term effects of CCHD can include delayed development and reduced stamina during exercise. Adults with these heart defects have an increased risk of abnormal heart rhythms, heart failure, sudden cardiac arrest, stroke, and premature death.\n\nAlthough babies with CCHD may appear healthy for the first few hours or days of life, signs and symptoms soon become apparent. These can include an abnormal heart sound during a heartbeat (heart murmur), rapid breathing (tachypnea), low blood pressure (hypotension), low levels of oxygen in the blood (hypoxemia), and a blue or purple tint to the skin caused by a shortage of oxygen (cyanosis). If untreated, CCHD can lead to shock, coma, and death. However, most people with CCHD now survive past infancy due to improvements in early detection, diagnosis, and treatment.\n\nCritical congenital heart disease (CCHD) is a term that refers to a group of serious heart defects that are present from birth. These abnormalities result from problems with the formation of one or more parts of the heart during the early stages of embryonic development. CCHD prevents the heart from pumping blood effectively or reduces the amount of oxygen in the blood. As a result, organs and tissues throughout the body do not receive enough oxygen, which can lead to organ damage and life-threatening complications. Individuals with CCHD usually require surgery soon after birth.
Interrupted aortic arch
MedGen UID:
57773
Concept ID:
C0152419
Congenital Abnormality
Non-continuity of the arch of aorta with an atretic point or absent segment.
Double aortic arch
MedGen UID:
488819
Concept ID:
C0265883
Congenital Abnormality
A conenital abnormality of the aortic arch in which the two embryonic aortc arches form a vascular ring that surrounds the trachea or esophagus and then join to form the descending aorta. Double aortic arch can cause symptoms because of compression of the esophagus (dysphagia, cyanosis while eating) or trachea (stridor).
Pulmonary artery atresia
MedGen UID:
82723
Concept ID:
C0265908
Congenital Abnormality
A congenital anomaly with a narrowing or complete absence of the opening between the right ventricle and the pulmonary artery.
Right aortic arch with mirror image branching
MedGen UID:
871216
Concept ID:
C4025695
Anatomical Abnormality
The aortic arch crosses the right mainstem bronchus and not the left mainstem bronchus, but does not result in the creation of a vascular ring. The first branch is the left brachiocephalic artery which divides into the left carotid artery and left subclavian artery, the second branch is the right carotid artery, the third branch is the right subclavian artery.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Abnormality of the ear
MedGen UID:
75618
Concept ID:
C0266589
Congenital Abnormality
An abnormality of the ear.
Aggressive behavior
MedGen UID:
1375
Concept ID:
C0001807
Individual Behavior
Behavior or an act aimed at harming a person, animal, or physical property (e.g., acts of physical violence; shouting, swearing, and using harsh language; slashing someone's tires).
Emotional lability
MedGen UID:
39319
Concept ID:
C0085633
Mental or Behavioral Dysfunction
Unstable emotional experiences and frequent mood changes; emotions that are easily aroused, intense, and/or disproportionate to events and circumstances.
Paranoia
MedGen UID:
306130
Concept ID:
C1456784
Mental or Behavioral Dysfunction
An inappropriate feeling of being persecuted or being the subject of hostility from others.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Specific learning disability
MedGen UID:
871302
Concept ID:
C4025790
Mental or Behavioral Dysfunction
Impairment of certain skills such as reading or writing, coordination, self-control, or attention that interfere with the ability to learn. The impairment is not related to a global deficiency of intelligence.
Inguinal hernia
MedGen UID:
6817
Concept ID:
C0019294
Finding
Protrusion of the contents of the abdominal cavity through the inguinal canal.
Umbilical hernia
MedGen UID:
9232
Concept ID:
C0019322
Anatomical Abnormality
Protrusion of abdominal contents through a defect in the abdominal wall musculature around the umbilicus. Skin and subcutaneous tissue overlie the defect.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Retrognathia
MedGen UID:
19766
Concept ID:
C0035353
Congenital Abnormality
An abnormality in which the mandible is mislocalised posteriorly.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Unilateral primary pulmonary dysgenesis
MedGen UID:
867233
Concept ID:
C4021592
Disease or Syndrome
Recurrent infections
MedGen UID:
65998
Concept ID:
C0239998
Finding
Increased susceptibility to infections.
Impaired T cell function
MedGen UID:
395415
Concept ID:
C1860127
Cell or Molecular Dysfunction
Abnormally reduced ability of T cells to perform their functions in cell-mediated immunity.
Hypocalcemia
MedGen UID:
5705
Concept ID:
C0020598
Disease or Syndrome
An abnormally decreased calcium concentration in the blood.
Hypernasal speech
MedGen UID:
107884
Concept ID:
C0566620
Finding
A type of speech characterized by the presence of an abnormally increased nasal airflow during speech associated with structural abnormality of the nasal passages.
Blepharophimosis
MedGen UID:
2670
Concept ID:
C0005744
Congenital Abnormality
A fixed reduction in the vertical distance between the upper and lower eyelids with short palpebral fissures.
Isolated Pierre-Robin syndrome
MedGen UID:
19310
Concept ID:
C0031900
Congenital Abnormality
Pierre Robin sequence is a craniofacial anomaly comprising mandibular hypoplasia, cleft secondary palate, and glossoptosis leading to life-threatening obstructive apnea and feeding difficulaties during the neonatal period (summary by Tan et al., 2013).
Velopharyngeal insufficiency
MedGen UID:
52992
Concept ID:
C0042454
Finding
Inability of velopharyngeal sphincter to sufficiently separate the nasal cavity from the oral cavity during speech.
Open mouth
MedGen UID:
116104
Concept ID:
C0240379
Finding
A facial appearance characterized by a permanently or nearly permanently opened mouth.
Bulbous nose
MedGen UID:
66013
Concept ID:
C0240543
Finding
Increased volume and globular shape of the anteroinferior aspect of the nose.
Submucous cleft hard palate
MedGen UID:
98472
Concept ID:
C0432103
Congenital Abnormality
Hard-palate submucous clefts are characterized by bony defects in the midline of the bony palate that are covered by the mucous membrane of the roof of the mouth. It may be possible to detect a submucous cleft hard palate upon palpation as a notch in the bony palate.
Underdeveloped nasal alae
MedGen UID:
322332
Concept ID:
C1834055
Congenital Abnormality
Thinned, deficient, or excessively arched ala nasi.
Narrow palpebral fissure
MedGen UID:
382506
Concept ID:
C2675021
Finding
Reduction in the vertical distance between the upper and lower eyelids.
Cleft palate
MedGen UID:
756015
Concept ID:
C2981150
Congenital Abnormality
Cleft palate is a developmental defect of the palate resulting from a failure of fusion of the palatine processes and manifesting as a separation of the roof of the mouth (soft and hard palate).
Hypoparathyroidism
MedGen UID:
6985
Concept ID:
C0020626
Disease or Syndrome
A condition caused by a deficiency of parathyroid hormone characterized by hypocalcemia and hyperphosphatemia.
Posterior embryotoxon
MedGen UID:
154282
Concept ID:
C0546967
Congenital Abnormality
A posterior embryotoxon is the presence of a prominent and anteriorly displaced line of Schwalbe.
Retinal vascular tortuosity
MedGen UID:
349827
Concept ID:
C1860475
Anatomical Abnormality
The presence of an increased number of twists and turns of the retinal blood vessels.

Professional guidelines

PubMed

Carrion P, Semaka A, Batallones R, Slomp C, Morris E, Inglis A, Moretti M, Austin J
J Genet Couns 2022 Feb;31(1):140-152. Epub 2021 Jul 5 doi: 10.1002/jgc4.1460. PMID: 34224608
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Curated

Schwinger E, Devriendt K, Rauch A, Philip N
Eur J Hum Genet 2010 Sep;18(9) Epub 2010 Feb 3 doi: 10.1038/ejhg.2010.5. PMID: 20125192Free PMC Article

Recent clinical studies

Etiology

O'Hora KP, Schleifer CH, Bearden CE
Curr Psychiatry Rep 2023 Oct;25(10):479-491. Epub 2023 Sep 18 doi: 10.1007/s11920-023-01444-6. PMID: 37721640Free PMC Article
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Jonas RK, Montojo CA, Bearden CE
Biol Psychiatry 2014 Mar 1;75(5):351-60. Epub 2013 Aug 28 doi: 10.1016/j.biopsych.2013.07.019. PMID: 23992925Free PMC Article
Gothelf D
Child Adolesc Psychiatr Clin N Am 2007 Jul;16(3):677-93. doi: 10.1016/j.chc.2007.03.005. PMID: 17562586

Diagnosis

O'Hora KP, Schleifer CH, Bearden CE
Curr Psychiatry Rep 2023 Oct;25(10):479-491. Epub 2023 Sep 18 doi: 10.1007/s11920-023-01444-6. PMID: 37721640Free PMC Article
Szczawińska-Popłonyk A, Schwartzmann E, Chmara Z, Głukowska A, Krysa T, Majchrzycki M, Olejnicki M, Ostrowska P, Babik J
Int J Mol Sci 2023 May 5;24(9) doi: 10.3390/ijms24098317. PMID: 37176024Free PMC Article
Burke S, Maramaldi P
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McDonald-McGinn DM, Sullivan KE
Medicine (Baltimore) 2011 Jan;90(1):1-18. doi: 10.1097/MD.0b013e3182060469. PMID: 21200182
Shprintzen RJ
Otolaryngol Clin North Am 2000 Dec;33(6):1217-40, vi. doi: 10.1016/s0030-6665(05)70278-4. PMID: 11449784

Therapy

Lu N, Kacin AJ, Shaffer AD, Stapleton AL
Otolaryngol Head Neck Surg 2023 Oct;169(4):1012-1019. Epub 2023 Mar 23 doi: 10.1002/ohn.331. PMID: 36950877
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Mosheva M, Korotkin L, Gur RE, Weizman A, Gothelf D
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Pediatrics 2003 Oct;112(4):e325. doi: 10.1542/peds.112.4.e325. PMID: 14523220

Prognosis

Brooks L, Raol N, Goudy S, Ivie C
Dysphagia 2022 Oct;37(5):1333-1336. Epub 2021 Oct 27 doi: 10.1007/s00455-021-10376-3. PMID: 34705083Free PMC Article
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Genet Med 2019 Oct;21(10):2328-2335. Epub 2019 Apr 5 doi: 10.1038/s41436-019-0509-y. PMID: 30948858Free PMC Article
Jiang L, Yang Y, Liu Q
J Craniofac Surg 2018 Oct;29(7):1709-1712. doi: 10.1097/SCS.0000000000004629. PMID: 29863556
Baek RM, Koo YT, Kim SJ, Kim JH, Kim JY, Kim BK
Plast Reconstr Surg 2013 Nov;132(5):806e-810e. doi: 10.1097/PRS.0b013e3182a3c14b. PMID: 23969952
Anderson PA
Curr Opin Cardiol 1994 Jan;9(1):78-90. doi: 10.1097/00001573-199401000-00010. PMID: 7911041

Clinical prediction guides

O'Hora KP, Kushan-Wells L, Schleifer CH, Cruz S, Hoftman GD, Jalbrzikowski M, Gur RE, Gur RC, Bearden CE
Autism Res 2023 Dec;16(12):2247-2262. Epub 2023 Nov 23 doi: 10.1002/aur.3049. PMID: 37997544Free PMC Article
Jiang L, Yang Y, Liu Q
J Craniofac Surg 2018 Oct;29(7):1709-1712. doi: 10.1097/SCS.0000000000004629. PMID: 29863556
Burke S, Maramaldi P
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Jonas RK, Montojo CA, Bearden CE
Biol Psychiatry 2014 Mar 1;75(5):351-60. Epub 2013 Aug 28 doi: 10.1016/j.biopsych.2013.07.019. PMID: 23992925Free PMC Article
Driscoll DA
Curr Opin Pediatr 1994 Dec;6(6):702-6. doi: 10.1097/00008480-199412000-00016. PMID: 7849818

Recent systematic reviews

Hankey PB, Ghulmiyyah J, Yeh HW, Tracy M, Arganbright J
Int J Pediatr Otorhinolaryngol 2022 Dec;163:111373. Epub 2022 Nov 2 doi: 10.1016/j.ijporl.2022.111373. PMID: 36335759
Mosheva M, Korotkin L, Gur RE, Weizman A, Gothelf D
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Orphanet J Rare Dis 2019 Aug 9;14(1):195. doi: 10.1186/s13023-019-1170-x. PMID: 31399107Free PMC Article
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Clin Otolaryngol 2017 Dec;42(6):1319-1328. Epub 2017 Apr 9 doi: 10.1111/coa.12874. PMID: 28322025

Supplemental Content

Table of contents

    Clinical resources

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    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.
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      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    • EuroGenetest, 2010
      Clinical utility gene card for: DiGeorge syndrome, velocardiofacial syndrome, Shprintzen syndrome, chromosome 22q11.2 deletion syndrome (22q11.2, TBX1)

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