22q13.3 deletion syndrome

Información en español Title

Other Names:

Phelan-McDermid syndrome; Deletion 22q13.3 syndrome; Chromosome 22q13.3 deletion syndrome; Phelan-McDermid syndrome; Deletion 22q13.3 syndrome; Chromosome 22q13.3 deletion syndrome; Monosomy 22q13; 22q13 deletion; 22q13.3 deletion; Monosomy 22q13.3 See More

Categories:

Congenital and Genetic Diseases; Nervous System Diseases

Summary Summary

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.^[1]^[2]^[3]

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.^[1]^[2] 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.^[2]

Last updated: 5/16/2018

Symptoms Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Accelerated skeletal maturation	Advanced bone age Early bone maturation [ more ]	0005616
Bruxism	Teeth grinding	0003763
Delayed speech and language development	Deficiency of speech development Delayed language development Delayed speech Delayed speech acquisition Delayed speech development Impaired speech and language development Impaired speech development Language delay Language delayed Language development deficit Late-onset speech development Poor language development Speech and language delay Speech and language difficulties Speech delay [ more ]	0000750
Hypoplastic toenails	Underdeveloped toenails	0001800
Impaired pain sensation	Decreased pain sensation	0007328
Macrotia	Large ears	0000400
Neonatal hypotonia	Low muscle tone, in neonatal onset	0001319
Tall stature	Increased body height	0000098
30%-79% of people have these symptoms
2-3 toe syndactyly	Webbed 2nd and 3rd toes	0004691
Autism		0000717
Autistic behavior		0000729
Broad-based gait	Wide based walk	0002136
Bulbous nose		0000414
Clinodactyly of the 5th finger	Permanent curving of the pinkie finger	0004209
Deeply set eye	Deep set eye Deep-set eyes Sunken eye [ more ]	0000490
Dental malocclusion	Misalignment of upper and lower dental arches Malalignment of upper and lower dental arches Bad bite [ more ]	0000689
Dolichocephaly	Long, narrow head Tall and narrow skull [ more ]	0000268
Episodic vomiting		0002572
Feeding difficulties	Feeding problems Poor feeding [ more ]	0011968
Full cheeks	Apple cheeks Big cheeks Increased size of cheeks Large cheeks [ more ]	0000293
Gastroesophageal reflux	Acid reflux Acid reflux disease Heartburn [ more ]	0002020
Heat intolerance	Intolerance to heat and fevers	0002046
High palate	Elevated palate Increased palatal height [ more ]	0000218
Hyperactivity	More active than typical	0000752
Hyperorality		0000710
Hypohidrosis	Decreased ability to sweat Sweating, decreased Decreased sweating [ more ]	0000966
Immunodeficiency	Decreased immune function	0002721
Large hands	large hand	0001176
Long eyelashes	Increased length of eyelashes Unusually long eyelashes [ more ]	0000527
Long philtrum		0000343
Lymphedema	Swelling caused by excess lymph fluid under skin	0001004
Malar flattening	Zygomatic flattening	0000272
Palpebral edema	Fullness of eyelids Puffy eyelids Puffy lids Swelling of eyelids [ more ]	0100540
Pointed chin	Pointy chin Witch's chin Small pointed chin [ more ]	0000307
Poor eye contact		0000817
Ptosis	Drooping upper eyelid	0000508
Sacral dimple	Spinal dimple	0000960
Strabismus	Cross-eyed Squint eyes Squint [ more ]	0000486
Thick eyebrow	Bushy eyebrows Dense eyebrow Heavy eyebrows Prominent eyebrows Thick eyebrows [ more ]	0000574
Unsteady gait	Unsteady walk	0002317
Wide nasal bridge	Broad nasal bridge Broad nasal root Broadened nasal bridge Increased breadth of bridge of nose Increased breadth of nasal bridge Increased width of bridge of nose Increased width of nasal bridge Nasal bridge broad Wide bridge of nose Widened nasal bridge [ more ]	0000431
5%-29% of people have these symptoms
Abnormality of the periventricular white matter		0002518
Agenesis of corpus callosum		0001274
Arachnoid cyst	Fluid-filled sac located in membrane surrounding brain or spinal cord	0100702
Cerebellar cortical atrophy		0008278
Delayed CNS myelination		0002188
Dental crowding	Crowded teeth Dental overcrowding Overcrowding of teeth [ more ]	0000678
Epicanthus	Prominent eye folds Eye folds [ more ]	0000286
Global developmental delay		0001263
Hair-pulling		0012167
Hearing impairment	Deafness Hearing defect [ more ]	0000365
Hydronephrosis		0000126
Hypermetropia	Farsightedness Long-sightedness [ more ]	0000540
Intellectual disability	Mental deficiency Mental retardation Mental retardation, nonspecific Mental-retardation [ more ]	0001249
Macrocephaly	Increased size of skull Large head Large head circumference [ more ]	0000256
Nausea and vomiting		0002017
Obesity	Having too much body fat	0001513
Patent ductus arteriosus		0001643
Polycystic kidney dysplasia		0000113
Recurrent pyelonephritis		0012787
Recurrent skin infections	Skin infections, recurrent	0001581
Renal dysplasia		0000110
Seizure		0001250
Umbilical hernia		0001537
Ventricular septal defect	Hole in heart wall separating two lower heart chambers	0001629
Ventriculomegaly		0002119
Vesicoureteral reflux		0000076
1%-4% of people have these symptoms
Aggressive behavior	Aggression Aggressive behaviour Aggressiveness [ more ]	0000718
Cellulitis	Bacterial infection of skin Skin infection [ more ]	0100658
Cerebral visual impairment		0100704
Generalized hypotonia	Decreased muscle tone Low muscle tone [ more ]	0001290
Hypertelorism	Wide-set eyes Widely spaced eyes [ more ]	0000316
Joint hypermobility	Double-Jointed Flexible joints Increased mobility of joints [ more ]	0001382
Microcephaly	Abnormally small skull Decreased circumference of cranium Decreased size of skull Reduced head circumference Small head circumference [ more ]	0000252
Micrognathia	Little lower jaw Small jaw Small lower jaw [ more ]	0000347
Recurrent infections	Frequent infections Frequent, severe infections Increased frequency of infection infections, recurrent Predisposition to infections Susceptibility to infection [ more ]	0002719
Tongue thrusting		0100703
Widely spaced teeth	Wide-spaced teeth Widely-spaced teeth [ more ]	0000687
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance		0000006
Concave nasal ridge	Boxer's nasal deformity Boxer's nose deformity Saddle nose Ski jump nose [ more ]	0011120
Hyporeflexia	Decreased reflex response Decreased reflexes [ more ]	0001265
Intellectual disability, moderate	IQ between 34 and 49	0002342
Motor delay		0001270
Prominent supraorbital ridges	Prominent brow	0000336
Protruding ear	Prominent ear Prominent ears [ more ]	0000411
Short chin	Decreased height of chin Short lower third of face [ more ]	0000331
Sporadic	No previous family history	0003745
Toenail dysplasia	Abnormal toenail development	0100797

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Last updated: 7/1/2020

Diagnosis Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
Orphanet lists international laboratories offering diagnostic testing for this condition.

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Related Diseases Related Diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnosis includes syndromes associated with hypotonia, developmental delay, speech delay and/or autistic-like behavior (Prader-Willi, Angelman, Williams, Smith-Magenis, Fragile X, Sotos, FG, trichorhinophalangeal and velocardiofacial syndromes, autism spectrum disorders and cerebral palsy; see these terms). Visit the Orphanet disease page for more information.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

ClinicalTrials.gov lists trials that are related to 22q13.3 deletion syndrome. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.
Orphanet lists European clinical trials, research studies, and patient registries enrolling people with this condition.

Patient Registry

Those with a 22q13 deletion are welcome to enroll in the Phelan-McDermid Syndrome International Registry, funded by the Phelan-McDermid Syndrome Foundation. The purpose of this registry is to consolidate information from individuals with Phelan-McDermid syndrome into a single database to promote research on this rare genetic condition. Additional information about Phelan-McDermid syndrome research can be found through the Phelan-McDermid Syndrome Data Network (PMS_DN).
The Developmental Synaptopathies Associated with TSC, PTEN and SHANK3 Mutations Consortium is an integrated group of academic medical centers, patient support organizations, and clinical research resources dedicated to conducting clinical research on Tuberous Sclerosis Complex (TSC1 and TSC2 genes), PTEN ASD/ID syndrome and Phelan-McDermid syndrome (PMS; SHANK3 gene). The Consortium has a contact registry for patients who wish to be contacted about clinical research opportunities and updates on the progress of the research projects.

For more information on the registry see: https://www.rarediseasesnetwork.org/registry/index.htm

Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Chromosome 22 Central
338 Spruce Street North
Timmins
Ontario
P4N 6N5
Canada
E-mail: info@c22c.org
Website: http://www.c22c.org/
Chromosome 22 Central - US Office
7108 Partinwood Drive
Fuquay-Varina, NC 27526
Telephone: 919-567-8167
E-mail: usinfo@c22c.org
Website: http://www.c22c.org
Chromosome Disorder Outreach (CDO)
PO Box 724
Boca Raton, FL 33429
Telephone: +1-561-395-4252
E-mail: https://chromodisorder.org/contact/
Website: https://chromodisorder.org/
Phelan-McDermid Syndrome Foundation
P.O. Box 1153
8 Sorrento Drive
Osprey, FL 34229
Telephone: 941-485-8000
E-mail: ronni@pmsf.org
Website: http://www.pmsf.org
Unique – Rare Chromosome Disorder Support Group
G1, The Stables
Station Road West
Surrey
RH8 9EE
United Kingdom
Telephone: +44 (0)1883 723356
E-mail: info@rarechromo.org
Website: https://www.rarechromo.org/

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Financial Resources

The Social Security Administration has included this condition in their Compassionate Allowances Initiative. This initiative speeds up the processing of disability claims for applicants with certain medical conditions that cause severe disability. More information about Compassionate Allowances and applying for Social Security disability is available online.

Parent and Caregiver Resources

In this NCATS Video Profile, Megan O’Boyle tells the story of her daughter, who has Phelan-McDermid syndrome.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

Genetics Home Reference (GHR) contains information on 22q13.3 deletion syndrome. This website is maintained by the National Library of Medicine.
The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.
Unique is a source of information and support to families and individuals affected by rare chromosome disorders. Click on the link to view information about 22q13.3deletion syndrome.

In-Depth Information

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss 22q13.3 deletion syndrome. Click on the link to view a sample search on this topic.

News & Events News & Events

News

NIH-Supported Research Survey to Examine Impact of COVID-19 on Rare Diseases Community
May 22, 2020
NCATS Translational Approach Addresses COVID-19
May 21, 2020

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Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

References References

Phelan K & Rogers C. Phelan-McDermid Syndrome. GeneReviews. August 2011; https://www.ncbi.nlm.nih.gov/books/NBK1198/.
De Rubeis S, Siper PM & Durkin A. Delineation of the genetic and clinical spectrum of Phelan-McDermid syndrome caused by SHANK3 point mutations. Mol Autism. April 27, 2018; 9:31. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5921983/.
Phelan K. What is Phelan-McDermid Syndrome? Medical Issues. Phelan-McDermid Syndrome Foundation. https://www.pmsf.org/what_is_pms/medical-issues/. Accessed 5/16/2018.

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