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Disease Profile

22q13.3 deletion syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Infancy

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ICD-10

Q93.5

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

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

Categories

Congenital and Genetic Diseases; Nervous System Diseases

Summary

22q13.3 deletion syndromealso 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]

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.

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
Delayed language development
Deficiency of speech development
Speech delay
Speech and language difficulties
Speech and language delay
Poor language development
Late-onset speech development
Language development deficit
Language delayed
Language delay
Impaired speech development
Impaired speech and language development
Delayed speech development
Delayed speech acquisition
Delayed speech

[ 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
Bad bite
Malalignment of upper and lower dental arches
Misalignment of upper and lower dental arches

[ 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
Decreased sweating
Sweating, decreased

[ more ]

0000966
Immunodeficiency
Decreased immune function
0002721
Large hands
large hand
0001176
Long eyelashes
Unusually long eyelashes
Increased length of 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
Squint eyes

[ more ]

0000486
Thick eyebrow
Bushy eyebrows
Dense eyebrow
Heavy eyebrows
Prominent eyebrows
Thick eyebrows

[ more ]

0000574
Unsteady gait
Unsteady walk
0002317
Wide nasal bridge
Nasal bridge broad
Wide bridge of nose
Widened 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

[ 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
Eye folds
Prominent eye folds

[ more ]

0000286
Global developmental delay
0001263
Hair-pulling
0012167
Hearing impairment
Hearing defect
Deafness

[ more ]

0000365
Hydronephrosis
0000126
Hypermetropia
Farsightedness
Long-sightedness

[ more ]

0000540
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249

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.

    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

      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.

          References

          1. Phelan K & Rogers C. Phelan-McDermid Syndrome. GeneReviews. August 2011; https://www.ncbi.nlm.nih.gov/books/NBK1198/.
          2. 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/.
          3. 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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