22q13.3 deletion syndrome
22q13.3 deletion syndrome, also known as Phelan-McDermid syndrome, is a genetic disorder that causes developmental delays, intellectual disability, and speech difficulties due to a loss of genetic material on chromosome 22.
Overview
22q13.3 deletion syndrome, commonly known as Phelan-McDermid syndrome, is a disorder caused by the loss of a small piece of chromosome 22 near the end of the chromosome at location q13.3.
Symptoms & Features
The features of 22q13.3 deletion syndrome vary widely and affect many parts of the body:
- Development and Cognition: Developmental delay, moderate to profound intellectual disability, and absent or delayed speech are characteristic. Some individuals experience developmental regression, losing skills they had already acquired.
- Behavioral Features: Many affected individuals have autism spectrum disorder or autistic-like characteristics, such as poor eye contact, sensitivity to touch, aggression, and chewing on non-food items like clothing.
- Neurological and Sensory Features: Decreased muscle tone (hypotonia), decreased sensitivity to pain, and occasionally seizures.
- Physical and Facial Features: Distinctive facial features include a long, narrow head; prominent ears; droopy eyelids (ptosis); a pointed chin; and deep-set eyes. Other physical traits include large, fleshy hands and feet, a fusion of the second and third toes (syndactyly), small or abnormal toenails, and rapid (accelerated) growth.
- Systemic Issues: A reduced ability to sweat (which increases the risk of overheating and dehydration), episodes of frequent vomiting and nausea (cyclic vomiting), and gastroesophageal reflux (backflow of stomach acids into the esophagus).
Frequency
More than 2,200 people worldwide have been diagnosed with 22q13.3 deletion syndrome.
Causes
The syndrome is caused by a deletion near the end of the long (q) arm of chromosome 22. The size of the deletion varies among individuals, and the loss of multiple genes in this region contributes to the symptoms:
- SHANK3: The loss of this specific gene is believed to be responsible for many of the major neurological features of the syndrome, including developmental delay, intellectual disability, and impaired speech.
- Ring Chromosome 22: In some cases, the syndrome is caused by a circular structure called a ring chromosome. This forms when a chromosome breaks in two places, loses its tips, and fuses its broken ends. If a break point occurs at position 22q13.3, the resulting loss of critical genes leads to the same symptoms as a simple deletion.
Inheritance
Most cases of 22q13.3 deletion syndrome are not inherited. The deletion typically occurs as a random event during the formation of reproductive cells (eggs or sperm) or in early fetal development. Affected individuals usually have no family history of the disorder, though they can pass the deletion to their children.
When the condition is inherited, its pattern is considered autosomal dominant because a deletion in a single copy of chromosome 22 in each cell is sufficient to cause the disorder. About 15 to 20 percent of affected individuals inherit the abnormality from an unaffected parent who carries a balanced translocation (a rearrangement where chromosome segments trade places without gaining or losing genetic material). When passed to the next generation, this translocation can become unbalanced, resulting in a child missing genetic material on the long arm of chromosome 22.
Other Names for This Condition
- 22q13 deletion syndrome
- Deletion 22q13 syndrome
- Deletion 22q13.3 syndrome
- Monosomy 22q13
- Phelan-McDermid syndrome