22q13.3 deletion syndrome

Alternate names

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

Definition

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.

Epidemiology

More than 2,200 people have been diagnosed with 22q13.3 deletion syndrome worldwide.

Cause

• 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.
• 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.

Inheritance

• Most cases of 22q13.3 deletion syndrome are not inherited.
• The deletion occurs most often as a random event during the formation of reproductive cells (eggs or sperm) or in early fetal development.
• Affected people typically have no history of the disorder in their family, though they can pass the chromosome deletion to their children.

Autosomal dominant pattern, a 50/50 chance.

• When 22q13.3 deletion syndrome is inherited, its inheritance pattern is considered autosomal dominant because a deletion in one copy of chromosome 22 in each cell is sufficient to cause the condition.
• About 15 to 20 percent of people with 22q13.3 deletion syndrome inherit a chromosome abnormality from an unaffected parent.
• In these cases, the parent carries a chromosomal rearrangement called a balanced translocation, in which a segment from one chromosome has traded places with a segment from another chromosome, but no genetic material is gained or lost.
• Balanced translocations usually do not cause any health problems; however, they can become unbalanced as they are passed to the next generation.
• Children who inherit an unbalanced translocation can have a chromosomal rearrangement with extra or missing genetic material.
• Individuals with 22q13.3 deletion syndrome who inherit an unbalanced translocation are missing genetic material from the long arm of chromosome 22, which results in the health problems characteristic of this disorder.

Signs and symptoms

• 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.

Diagnosis

• The diagnosis of Phelan-McDermid syndrome is is done by clinical findings and by finding of a heterozygous deletion of chromosome 22q13.3 with involvement of at least part of SHANK3 gene, or a heterozygous pathogenic variant in SHANK3 on molecular genetic testing.
• Individuals can be diagnosed by chromosomal microarray must have a karyotype to evaluate for the presence of a ring chromosome 22.[1].

Treatment

• Early referral for developmental support / special education
• Assistive technology for communication
• Oral-motor therapy to alleviate chewing and swallowing problems
• Standard treatment of seizures,hearing loss
• Recurrent ear infection, visual problems, and other identified medical needs.
• Regular professional dental hygiene, routine brushing, and fluoride treatment are important as enamel may be damaged from persistent chewing.[2].

NIH genetic and rare disease info

• NIH info on 22q13.3 deletion syndrome

22q13.3 deletion syndrome is a rare disease.

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