22q13 Deletion Syndrome
The 22q13 deletion syndrome is a microdeletion syndrome. It results from missing a small segment of genetic material on the end of the long arm (q) of chromosome 22. The condition was first described in the literature in the 1980s. Individuals with the condition have a variety of features. The most common features are developmental delay, delayed or absent speech, and weak muscles (also known as hypotonia or low muscle tone).
In 2004, the 22q13 Deletion Syndrome Foundation voted to give the condition a second name. They named it Phelan-McDermid syndrome. Phelan and McDermid are the names of the doctors known for their research on 22q13 deletion syndrome. The condition can be called by either name.
The 22q13 deletion syndrome results from a chromosome difference. People typically have 23 pairs of chromosomes. The first 22 chromosomes are called auto-somes and are numbered one to 22. The last pair are the sex chromosomes, identified as X and Y. Each chromosome has a long part (q) and a short part (p). Packed in the chromosomes are genes, which are important because they determine how a person grows, develops, and functions. They also determine physical features of an individual, such as eye color and the shape of a person's face. When a person's genes are missing or not working properly, the result can be health problems, learning difficulties, and/or physical differences.
Individuals with 22q13 deletion syndrome are missing part of a chromosome. The syndrome's name provides the location of the missing part. It is on the long arm of chromosome 22 at the very end (location q13). Since the 22q13 region contains genes, people missing it do not have all the proper instructions for development. As a result, they have similar learning difficulties, physical differences, and behavior problems.
The 22q13 deletion syndrome is caused by an absence of genetic material on chromosome 22. As of 2005, the specific genes involved in 22q13 deletion syndrome had not been identified. However, several candidate genes had been located to the 22q13 region, including SHANK3, ACR, and RABL2B. Researchers believe an absence of SHANK3 may cause the neurological features of mental retardation and speech delay.
When a person is diagnosed with 22q13 deletion syndrome, it is usually the first time it has been seen in the family. For most parents, the chance of having a second child with the condition is low. In some families, however, an increased risk exists for having a second child with the syndrome. In these families, a parent usually has a balanced translocation, which means that parent has the correct amount of chromosome material, but the material is rearranged. The rearrangement usually does not cause problems in the parent. However, when the parent has a child, the child may receive extra or missing pieces of chromosome material.
If a parent has a balanced translocation involving the 22q13 region, he or she may be at risk of having multiple children with the syndrome. Therefore, parents of a child with 22q13 deletion syndrome should consider testing for balanced translocations. Parents who are found to carry a translocation may decide to pursue prenatal diagnosis for future pregnancies. If an individual with 22q13 deletion syndrome had children, he or she would have a 50% chance of having a child with the condition and a 50% chance of having a child without the condition. As
The 22q13 deletion syndrome affects males, females, and all ethnicities. It is not known how many people have 22q13 deletion syndrome. The syndrome is considered rare and researchers believe it is often underdiagnosed.
Signs and symptoms
Individuals with 22q13 deletion syndrome have a variety of symptoms. In addition, the severity of each feature ranges from mild to severe. Therefore, two people with the syndrome may have very different characteristics. The characteristics most commonly seen are developmental delay, low muscle tone, speech difficulties (lack of speech or absence of speech), and advanced growth. Many individuals also have behavior differences, including autistic-like behavior and/or excessive chewing.
In addition, some children learn a specific skill and lose it. The medical term for the loss of a skill is regression. When children with the condition lose a skill, it is usually in the area of speech. Other characteristics that are not as common in the syndrome, but have been reported include drooping eyelids, large head, webbing between the second and third toes, large hands, lack of sweat, seizures, flaky toenails, and different shaped ears, skull, and/or forehead.
The diagnosis is made by determining the 22q13 chromosome region is missing. Sometimes the deletion of chromosome 22 can be seen by a routine chromosome analysis. Often, however, the deletion is difficult to see and a special test called Fluorescence In Situ Hybridization (FISH) is used. FISH is a molecular cytogenetic technique. It utilizes fluorescent probes to examine the presence or location of specific chromosomes, chromosome regions, or genes. Researchers can determine the presence and location of the probes by looking at them with a microscope. The light causes the fluorescent tag on the probe to glow.
For 22q13 deletion syndrome, a fluorescent probe specific for region 13 on the long arm of chromosome 22 is used. Since people with 22q13 deletion syndrome have one chromosome with the region and one without it, the probe will bind once. Individuals without the syndrome have two copies of the region, so the probes bind twice. As a result, researchers see one fluorescent mark for the 22q13 region in individuals with the syndrome and two fluorescent marks in individuals without the syndrome.
As of 2005, several suggestions regarding testing for the condition were present in the literature. It was suggested that physicians should consider testing babies with an unknown cause of weak muscles at birth. Physicians should also test individuals with severe speech delay and autistic-like behavior or people with developmental delay, absent or delayed speech, and physical differences.
Treatment and management
Treatment for 22q13 varies depending on the presenting symptoms and physical differences. Individuals may see a variety of specialists, including geneticists, psychologists, and neurologists. Most people with the syndrome receive speech, occupational, and/or physical therapy. Each type of therapy helps with specific features of the syndrome. For example, speech therapy can help improve communication, occupational therapy can assist in developing life skills, and physical therapy can help strengthen muscles.
Support groups and resources are available for individuals with 22q13 deletion syndrome and their families. Information can be obtained through the 22q13 Deletion Syndrome Foundation.
In general, most individuals with 22q13 deletion syndrome need help and supervision all of their lives. However, the specific prognosis varies with each person, depending on their characteristics. For example, an individual with mild mental retardation and a few physical differences would be expected to have a better prognosis than a person with severe mental retardation, no speech, and behavior problems. Also, some individuals will have regression or loss of a specific skill, especially in the area of speech. It is not possible to determine which people will lose skills.
Manning, M. A., et al. "Terminal 22q Deletion Syndrome: A Newly Recognized Cause of Speech and Language Disability in the Autism Spectrum." Pediatrics 114, no. 2 (August 2004): 451–457.
Phelan, M. C., et al. "22q13 Deletion Syndrome." American Journal of Medical Genetics 101 (2001): 91–99.
.22q13 Deletion Syndrome Foundation. 250 East Broadway, Maryville, TN 37804. (800) 932-2943. (April 4, 2005.) <http://www.22q13.com>.
Chromosome 22 Central. 237 Kent Avenue, Timmins, ON Canada P4N 3C2. (705) 268-3099. (April 4, 2005.) <http://www.c22c.org>.
Cristi Radford, BS
Gail Stapleton, MS