Phelan-McDermid Syndrome and Shank 3 Mutations
- Publish Date: 2011/03/10 - (Rev. 2018/03/14)
- Author: Thomas C. Weiss
- Contact : Disabled World
Outline: Phelan-McDermid syndrome is characterized by average to accelerated growth low muscle tone moderate to profound intellectual disability severely delayed speech as well as some dysmorphic feature.
Phelan-McDermid syndrome, also referred to as, '22q13 Deletion Syndrome,' is caused by the loss or absence of genes located at the tip of the twenty-second chromosome and a lack of the Shank3 ProSAP2 gene that is suspected as the main cause of symptoms related to the syndrome.
The gene plays a large part in the development of the human nervous system, to include a person's brain. Loss of the gene prevents appropriate nervous system development while a person is still in the fetal development stage.
Phelan-McDermid syndrome is commonly believed to be characterized by average to accelerated growth, low muscle tone, moderate to profound intellectual disability, severely delayed speech, as well as some dysmorphic features. A very small portion of the population with the syndrome experience submicroscopic deletions of their 22q13 genes, resulting in mild developmental delay. Research has suggested that the inability of the Shank3 ProSAP2 gene to produce enough protein for average functioning might be responsible for the majority of neurological symptoms a person with the syndrome experiences, such as absent speech or developmental delay.
There is a range in the severity of symptoms people with the syndrome experience, yet the majority have severe physical and intellectual developmental delays. People with Phelan-McDermid syndrome have particular difficulties with speaking and communicating. Extremely low muscle tone is a trait of the syndrome. People who have the syndrome also experience difficulties with sleeping, emotional stability, and eating.
As of the year 2009, there were approximately 500 people with Phelan-McDermid syndrome in the world, including both children and adults. The majority of the people who have this disability are small children. Recently, a reliable test for the syndrome called the, 'Flourescence In Situ Hybridization Test,' or, 'FISH,' test has become available. The actual number of people with this form of disability is certain to be much larger than current numbers indicate. Support groups pursue outreach efforts to assist families with older children.
The majority, although not every person with Phelan-McDermid syndrome, has various characteristic features such as:
- Delayed or absent speech
- Normal growth or may be tall for age
- Newborns usually have floppy muscle tone
- Delayed in sitting up, rolling over, crawling and walking
- Newborns/Infants have a difficult time drinking from the bottle
A child with Phelan-McDermid syndrome's facial features may be somewhat subtle; a doctor may not recognize the features in association with the syndrome. The child may have puffiness around their eyes, a long head shape, droopy eyelids, long eyelashes, large ears and puffy cheeks. They may also have underdeveloped toenails that peel off easily, fleshy and large hands, an inability to perspire leading the child to overheat easily.
Diagnosing Phelan-McDermid Syndrome
Phelan-McDermid syndrome is diagnosed through a study of the person's chromosomes, commonly through a sample of their blood. The chromosome deletion is many times hard to find through a routine chromosome study. The more recent FISH test is used more often if the syndrome is suspected.
Through a FISH study, a DNA probe that is specific for the tip of the long arm of chromosome 22 is used to find if the 22q13 segment is either present or absent. Should a child have Phelan-McDermid syndrome, the 22q13 region will be present on their normal chromosome, yet absent on the deleted chromosome. The deletion may also be detected in a child's skin cells, or in cells that have been obtained through prenatal diagnostic testing.
Treatment of Phelan-McDermid Manifestations
Various treatment options are available for symptoms related to Phelan-McDermid syndrome. For example; oral-motor therapy can be pursued in relation to chewing and swallowing problems, as well as standard treatments for gastroesophageal reflux. Treatment methods can also be pursued in relation to other problems that arise or exist in relation to the syndrome such as:
- recurrent ear infection
or other issues. Physical and occupational therapies, as well as exercise, can be pursued in order to improve the person's strength and coordination. Augmented communication strategies can assist with the person's speech and communication. Medication can help with anxiety, hyperactivity, and self-stimulatory behaviors. An orthodontist can provide therapy for malocclusion.
Another form of treatment for children with Phelan-McDermid syndrome involves the administration of intranasal insulin. Children with the syndrome who received this form of treatment demonstrated a marked short-term improvement in both their gross and fine motor activities, as well as their cognitive functioning and educational level. Positive long term effects were noted in the nonverbal communicating of children receiving this medication. Of the potential side-effects, there is potential for changes in balance, general loss of interest, or extreme sensitivity to touch.
The SHANK3 gene is located on chromosome 22 and is one of a number of genes that belong to the SHANK family of genes. The Shank family has three known members that include SHANK1, SHANK2, and SHANK3. Shank proteins are vital to brain cell communication; they have a crucial role in the formation of connections between a person's nerve cells.
Dr. Joseph D. Buxbaum, Director of the Seaver Autism Center and Professor of Psychiatry, Neuroscience, and Genetics and Genomic Sciences at Mount Sinai School of Medicine states:
"SHANK3 is of great interest to us because it has been shown to be the gene associated with neuro-behavioral symptoms in individuals with PMS. The deletion or alteration of SHANK3 interferes with appropriate nerve cell function and nerve cell communication. Understanding the function of SHANK3 would help lead to the development of more targeted treatments for PMS and SHANK3 mutations and will also lead to better treatments in autism spectrum disorders."
People who experience a mutation in SHANK3 demonstrate absent or delayed speech, intellectual disability, poor muscle tone, and minor body and facial abnormalities in general, just as people with Phelan-McDermid syndrome do.
They also demonstrate behavioral symptoms which fall in the category of an Autism Spectrum Disorder (ASD). One estimate states that approximately one-percent of people with an ASD also have a deletion or mutation of SHANK3.
Genetic sequencing may identify a mutation on chromosome 22. There is a test referred to as an, 'array comparative genomic hybridization, ' or, 'aCGH,' that has the ability to specifically identify the deletion on the q13 portion of chromosome 22.
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