Posture issues associated with WS

Anyone familiar with someone with williams syndrome knows that the majority of individuals have an unusual posture.  Their backs may sway and their bellies stick out in front.  They may also walk with a stagger or in an uncoordinated fashion.  Part of this has to do with spatial awareness and muscle coordination (see other blog posts on these topics).  As an individual ages, these muscle abnormalities can take a toll on their posture.  This is the main cause to some of the spinal issues that can develop in someone with WS.

Williams syndrome can be associated with various issues related to the spine- lordosis and kyphosis being the most common; scoliosis being the least.  Lordosis and kyphosis typically develop during adolescence and/or adulthood and are preventable.  Scoliosis may develop late in childhood.  Research on WS individuals with scoliosis indicates that it may be coupled with other inheritable mutations outside the WS area and are linked to familial inheritance.

Bends in the spine due to muscle tone

Lordosis is commonly called swayback.  It is when the spine has a pronounced curve in the lower back, called the lumbar region which can cause a belly that sticks out further than normal.  It is the most common postural issue in WS, found in 38% of individuals.



Kyphosis is also known as humpback.  This is when the spine typically curves outwards towards the back of a person.  This condition is most common in the upper back just below the shoulder blades and behind the chest.  It is found in 20% of individuals with WS.





The causes of kyphosis and lordosis in WS are rooted in two issues- the missing elastin (ELN) gene and the muscle tone of the lower extremities.  Elastin deletion is the underlying genetic mutation used to diagnose WS.  Elastin is a protein found in many connective tissues of the body that give the tissue both strength and flexibility.  It can work much like a spring, allowing the tissue to lengthen but bounce back and retain its original structure.  It is found in virtually every organ in the body and arranged in a way to improve the function of the structure.  For example, it is found in rings around the arteries, in strips down a ligament or in net like sheets within the skin. 



Most notably in kyphosis and lordosis, the lack of elastin can cause ligaments that support the vertebrae to loose their strength.  There are several sets of ligaments that cradle the vertebrae.  The anterior longitudinal ligaments run long ways down the body of the vertebrae.  This is the section of the vertebrae most central to the body, or towards the front.  The posterior longitudinal ligaments run beneath the spinal process or points of the spine on the back side of the vertebrae.  This is the area that you would touch if you ran your hand down your back.  Both of these sets of ligaments are arranged with a connective tissue called dense regular tissue.  This tissue has long sections of collagen and elastin that are packed tightly together and all run in the same direction.  This allows some give to the ligament but due to the direction of the fibers, gives strength in the direction of the primary force (supporting the weight of the body on the pelvis).  When there is less elastin, the ligaments become looser and strength is reduced.  This can cause the vertebrae to slip out of alignment and compress the intervertebral discs in an abnormal fashion.



The second issue with kyphosis and lordosis is muscle contractures or high tone in the lower extremities.  Contractures are tightening of muscles due to increased tone.  The contraction of the muscle pulls with extra force on tendons.  This in turn can pull on bones and create an uneven posture, affecting bone alignment and the development of kyphosis or lordosis.  It is important for individuals with WS to monitor their muscle tightness, especially in the legs and hips and to stretch them so that contractures do not get severe and cause further debilitating symptoms.  (See my blog post on muscles for more information on this.)  The prevalence of lordosis and kyphosis in WS is attributed to the muscle contractures that often occur in the lower body, particularly the hips, and lax joints due to the missing elastin in the ligaments of the spine.

The tightening of the muscles are much more common in adults with WS than in children and postural issues tend to be very mild. These conditions are preventable through physical therapy. Typically children with williams syndrome receive physical therapy at an early age but as they reach adolescence that service often ceases. It is suggested that adults with WS get physical therapy evaluations occasionally to determine if kyphosis or lordosis is occurring due to tight muscles in the lower body.  Stretching the tight muscles is the easiest and best preventive treatment you can take to avoid these issues.  If muscles become very tight, it is important to get further treatment from a physical therapist and to see orthopedics.  Some individuals will be fitted with orthodics that are designed to sustain a long stretch, sometimes overnight to treat the muscle.  Nurturing muscle health is the primary way to treat kyphosis and lordosis related to WS.

Scoliosis

Unlike kyphosis and lordosis being the prevalent postural issues in WS adults, some individuals are born with or develop scolisis at a young age.  Scoliosis is a curvature to the side.  These can often be in a C shape or S shape.  It is found in 12% of individuals with WS, which is considered a low incidence and typically presents itself by the 8th birthday. 



Scoliosis is known in the general population to be caused by a mutation on the fibrillin 1 (FBN1) gene, which is NOT in the WS region.  It is found on chromosome 15.  In all individuals with scoliosis in the general population, research indicates that this mutation accounts for 60% of cases.  FBN1 is known to affect the ability for the body to properly create strong elastin.  This is similar to the WS deletion which affects elastin's ability to bounce back under stress.  The difference between the two causes of scoliosis is that those with the FBN1 mutation are more likely to develop scoliosis than those with WS, showing that the FBN1 gene more negatively affects elastin's strength in terms of spinal development.      . 

In Williams syndrome, scoliosis can be linked to a specific gene mutation in conjuction with the classic deletion in the WS region.  The mutation is on a gene called SERPINA1.  SERPINA1 is a gene that is responsible for creating a protein called α-1-antitrypsin (AAT for short).  An AAT mutation is relatively common in the general population.  If a person inherits the mutation on both of their genes it can cause serious health issues such as emphysema and liver disorder, although, a double mutation is rare.  Carriers of one mutated gene can also have adverse health issues, such as scoliosis.  Since many people carry this mutation on the SERPINA1 gene, it is possible that some individuals with WS would also be carriers.  Researchers believe that this is the connection between a low incidence of scoliosis with WS. 

AAT is a protein that is an inhibitor of an enzyme.  Enzymes are proteins that help speed up reactions within the body.  Without them our body would not be able to survive.  The functioning of the body is basically a collection of complicated chemical reactions.  Most of these chemical reactions wouldn't take place fast enough for us to survive so we have proteins called enzymes that reduce the amount of energy needed for those reactions to take place.  We have thousands of enzymes in the body, each made to help speed up one particular reaction that we rely on for survival. 



The AAT protein affects an enyme called elastase.  Elastase is used by the body to reorganize elastin in the connective tissues.   When the body is laying down elastin in large amounts, usually during rapid growth at the end of pregnancy and throughout the first year of life, the body undergoes large amounts of physical stress.  This stress can create some inflammation within tissues, such as connective tissue.  The body's response to this is to repair the tissue by breaking down the damaged elastin fibers and replacing them with new.  The enzyme used to break down the elastin is elastase. 

With every enzyme it is important for the body to have a counteractive protein to control its reactions.  Enzymes are renewable meaning after they perform their desired reaction, they can disconnect from the substrate (or molecule they are breaking) and work on another.  In the case with elastase, it would break down a portion of elastin and then disconnect and work on another.  Therefore, the body makes a second protein, called an inhibitor, that slows down or stops the action of an enzyme within the body.  This is the body's way of preventing too much degradation of the elastin proteins.  When an individual has a mutation on the SERPINA1 gene, they fail to make enough of the AAT protein which is elastase's inhibitor.  This means that their body can not slow down elastase from destroying elastin, causing an absence of elastin in areas of the body such as the joints.



The destruction of elastin by AAT coupled with the inability to make elastin by the WS deletion is thought to be the main reason why some individuals (about 12%) with WS have scoliosis.  The lack of the elastin compromises the structure of the discs that are in between the vertebral bones that function to cushion the vertebrae.  An intervetebral disc is structured with a ball-shaped section of cartilage that is in the center, called the nucleus pulposis.  This area of the intervertebral disc is very dense with elastic fibers that are designed to compress and absorb stress from the weight of your body on the vertebrae.  In fact, over the course of a day the discs are said to actually be thinner than when you first wake up.  This is the nature of the elastin, absorbing the force and then springing back to it's original shape.  Circling around the nucleus pulposis are rings of connective tissue called the anulus.  The anulus has connective tissues thick with collagen (fibers designed for strength) that alternate with rings of elastic fibers for flexibility.  As you get closer to the center of the rings, the elastic fibers increase in number and are organized in a way where they sit against each other in different angles than its neighboring rings.  The structure of these layers reflect the function of the disc (giving it strength from pressure in various directions). 



Knowing the structure of intervertebral discs, it's not surprising to find that the lack of elastin can devastate the integrity of the structure.  When a child goes through stages of rapid growth, the intervertebral disc, the bone in the spine and the ligaments that support those structures undergo a drastic change in force placed on them by the body.  This can cause stress on the tissues and minor injuries.  The distressed tissue will release chemicals indicating that it is injured, activating elastase, the enzyme designed to destroy elastin.  If a individual has the AAT mutation, it is difficult for their body to reduce or stop this enzyme action resulting in lower levels of elastin in the body.  Coupled with the inability for the body to make adequate amounts of elastin (due to the WS ELN deletion), the intervetebral discs and ligaments can lose their strength and fall out of alignment, resulting in curvature of the spine- scoliosis.

The spine or vertebrae are normally positioned in a way that they sit directly over the pelvis.  Their primary function is to protect the spinal cord but they also contain a large base that absorbs much of the body's weight and allows us to stand erect and walk on two legs.  When the spine is displaced such as in these issues, it can cause back pain, putting additional stress on the muscles of the back, and awkward gait when walking since the body is not positioned properly in line with the pelvis.

Other rarer conditions related to the spine

Some WS individuals may develop kyphoscoliosis which is a combination of kyphosis in the upper back and scoliosis.  This condition is often due to having hypertonic (high tone in the legs and hips) coupled with hypotonia in the core of the body (low tone of the muscles).  In addition to the unbalanced tone in the muscles, the muscles have a lax nature due to elastin deficiencey in the tendons that attach them to the spine and in the ligaments that connect each vertebrae to one another.  Rarely if this occurs there can be a large curvature inwards that puts pressure on the heart and lungs and could create a need for surgery.  Incidences of this occurring are all recorded in children.

Treatments of scoliosis

Doctors and schools typically check for scoliosis between the ages of 8 to 10.  They will often look at the curvature of the spine by having the child bend and touch their toes.  If scoliosis is suspected, x rays will follow to determine if there is a degree of curvature.  Anything less than 25 degrees is typically not treated, just followed to be sure it doesn't progress.  If the curvature is 25-30 degrees, a back brace may be fitted.  Curves greater than 30 degrees will often lead to surgical repair where they fuse the vertebrae or insert metal rods to support it.  Surgery and treatment is always determined based on the patient, their needs and how much growth they still have in their future.

Sources used:

• Understanding Williams Syndrome: Behavioral Patterns and Interventions By Eleanor Messing Semel, Sue R. Rosner
• Neurogenetic Developmental Disorders: Variation Of Manifestation in Childhood By Michele M. M. Mazzocco, Ph.D., Judith L. Ross
• Alpha 1 antitrypsin deficiency alleles are associated with joint dislocation and scoliosis in Williams syndrome; Colleen A. Morris, Ariel M. Pani, Carolyn B. Mervis, Cecilia M. Rios, Doris J. Kistler, and Ronald G. Gregg.
• http://www.emedicinehealth.com/scoliosis/article_em.htm
   

Williams syndrome behavior profile- ADHD

Many people are familiar with the symptoms of attention deficit/hyperactivity disorder.  You envision a child who can't sit still nor concentrate on anything for very long.  In the Williams syndrome community, it is not unlikely to find many of the individuals diagnosed with ADHD.  Many individuals with WS have a very hard time paying attention to a task for a prolonged period of time.  In my own experience we noticed inattentive issues from a very early age of one.  Katie has trouble paying attention to a task during therapy for longer than only a few minutes, especially if it's a task that she doesn't enjoy.  We have since used strategies to help her remain focused, such as centering activities around highly motivating topics, using music, sometimes eliminating objects that are too interesting to the point she won't do anything else and reducing environmental distractions.  Considering she is only three, I foresee us needing to explore the ADHD topic in her future, but for now we use these strategies.  Many families find that help from a psychologist is necessary for their child to be successful at home and school.  This blog post is dedicated to them.

ADHD is tricky to treat...

In today's age, ADHD is so mainstream the acronym has become a term used in every day language.  Its diagnosis in children has increased so much over the past 10-20 years that many believe students today are over diagnosed.  With over diagnosis, many feel that kids are also over medicated. In the clinical world, however, psychologists see patients improving with the treatments and argue that ADHD is diagnosed more today than in the past because we are becoming more educated about the symptoms.  Parents and educators can identify kids who need help better now than in the past.  Psychologists don't see patients as unmotivated, lazy or free spirits.  They see them as a person with a brain that functions differently and one that can be treated when they work closely with a physician.  The increase in awareness has lead to more people receiving diagnoses and getting the treatment that they need to become more focused and successful.

ADHD is becoming more and more understood over time and as new research has answered baffling questions, the medical and psychological treatments offered have improved.  Despite the improvements, ADHD is a very frustrating condition for parents, doctors and educators to address because the basis of the condition is centered around brain chemistry which can be very complicated.  The variety of medications and the differences between how people's brains react to them can make treatment a long endeavor.  You often have to start with what works for most and modify it with different combinations of medications and/or change medication schedules. 

Another reason ADHD is so hard to treat is because it is often found paired with another disorder.   Those with ADHD also tend to display other psychiatric disorders such as anxiety, learning or behavioral disorders or mood disorders.  This rings true in WS, especially with anxiety, making the combinations of treatments very tricky to find the right balance.  When treating ADHD, the treatment has to mesh with all the psychiatric disorders and often symptoms of one will mask symptoms of another, complicating treatment.  This is why a child will often be put on one type of medication and will have to be carefully monitored to insure there aren't any adverse symptoms.

Research has also furthered our understanding of the variety of symptoms of ADHD.  It was once thought that ADHD was more prevalent in boys than in girls and the symptoms of hyperactivity.  Today we know that there are various forms of ADHD that affect both genders.  Research also indicates that 50% of children with ADHD don't actually grow out of it, the symptoms just change and the person often adapts.  The condition, though, will still affect them throughout life.  They have found that kids who are hyperactive and impulsive will shift as they age from the hyperactive classification towards a more inattentive classification.  Their outward behavior may change indicating that they have "grown out of ADHD" but in reality the inattentive state is easier to mask or is often misunderstood.  It is seen as a chosen behavior rather than a psychological disability.

Diagnosing ADHD

The classification system for ADHD has frequently changed in the past.  Today psychiatrists diagnose patients as Attention deficit-hyperactivity disorder followed by three types- inattentive type, hyperactive-impulsive type or a combination type. 

All of us have experienced periods of inattentiveness or hyperactivity throughout times in our lives. The difference between an energetic kid and one with ADHD is that they have to have 6 out of the 9 behaviors outlined as ADHD and it must interfere with their normal functioning at TWO aspects of life: at school, work, social settings and/or at home for a period of 6 months or more. Here is a list of the behaviors associated with this condition (from the National Resource center of ADIHD):

"Criteria for the three primary subtypes are: ADHD - Predominantly Inattentive Type

• Fails to give close attention to details or makes careless mistakes.
• Has difficulty sustaining attention.
• Does not appear to listen.
• Struggles to follow through on instructions.
• Has difficulty with organization.
• Avoids or dislikes tasks requiring sustained mental effort.
• Loses things.
• Is easily distracted.
• Is forgetful in daily activities.

ADHD - Predominantly Hyperactive/Impulsive Type

• Fidgets with hands or feet or squirms in chair.
• Has difficulty remaining seated.
• Runs about or climbs excessively.
• Difficulty engaging in activities quietly.
• Acts as if driven by a motor.
• Talks excessively.
• Blurts out answers before questions have been completed.
• Difficulty waiting or taking turns.
• Interrupts or intrudes upon others.

ADHD - Combined Type

• Individual meets both sets of inattention and hyperactive/impulsive criteria."

The science behind ADHD

There is still a lot to learn about the cause of ADHD. Scientists know that it has to do with the brain chemistry and neural connections. There is some evidence that certain environmental factors contribute to this condition but the current belief is that it is genetic and a child's environment can contribute to the severity of the symptoms (such as aggravating the condition due to food allergies or environmental toxins)

ADHD has been identified as a disorder of the brain's ability to coordinate its executive functions. In an average person, the brain has neural pathways that coordinate your working memory, your ability to organize a task and your use of internal language where you think through and "talk to yourself" in order to make sense and coordinate a task. All of these tasks are difficult for someone with ADHD because those neural pathways do not work as efficiently as they should.

Brown et al. explains this impairment of executive function as being synonymous to a type of leadership role. Think of a conductor of an orchestra who has to coordinate several types of musicians to play at the right time and tempo in order to produce beautiful harmony. Your brain works in much of the same way. You are receiving information from your environment and you need to choose what to act on, pull from memory on how to act on it, coordinate muscles and glands to produce the right combinations of actions, etc. It takes quite a bit of organization for your brain to maintain this task. This executive function of coordinating all the thoughts, memories, actions and interpreting the information your getting is coordinated by the executive function of the brain. The very place where ADHD has deficits.

Furthermore, as a person ages, they are called upon to use this executive function more and more. As a youngster, kids are hyper, they don't have big responsibilities and as they age they will be challenged more and more to use that executive function. This is why the inattentiveness becomes more apparent as a child ages. Often if a child doesn't have the hyperactive part of ADHD, they aren't even diagnosed as having inattentiveness until they reach middle-high school where they are called upon to take on more responsibility.

In addition to executive functions, those with ADHD have deficits in their working memory. Your working memory is a portion of your brain that takes information from the long term storage of memory and puts it into action. Basically its like opening a file cabinet of things you know and reading a folder you need to use at the moment. It is linked to acting on what you know, making connections between what you are learning to what you have learned and it is essential for understanding and initiating tasks. Deficits in this area will lead to students who don't finish tasks or have trouble starting them. 

There are emotional ties to those with ADHD as well. They often become hyper focused on something interesting and although they know they should be engaged in another activity and that if they don't it will cause them "trouble" down the road, they physically cannot find attention for the less interesting stimulus. This type of ADHD is often coupled with other psychological disorders such as mood disorders.

Research is unclear on the actual brain science that causes ADHD. Much of the early research has pointed to the neural pathways in the pre-frontal cortex (the portion of your brain behind your forehead). This area of the brain is what creates your personality, your ability to problem solve and think through academics. It essentially is the part of the brain that makes you, well, you. Later research indicates that, yes, this area of the brain is affected, but so are neural pathways or highways between memory in the thalamus, deep in the center of the brain and the parietal lobe where sensory information is processed in the top back of your brain. All these areas must coordinate efforts to produce a behavior and this is the essential workings of that executive function of the brain.

There is also evidence that brain chemistry has a lot to do with ADHD, particularly, dopamine. Dopamine is a neurotransmitter, a tiny chemical that is made by cells in the brain that allow one neuron to communicate with another. It is thought that ADHD has a deficit of dopamine and
catecholamines. There is a lot left to understand about this chemistry but it is widely known that medication that focuses on the increase of dopamine is effective in preventing inattentiveness in those with ADHD.


Treating ADHD in someone with WS is extra tricky...

More than 50% of individuals with Williams syndrome are diagnosed with ADD or ADHD. In studies, children with WS were compared to those with ADHD with comparable verbal abilities versus a control group of typical children. The children with WS were most like those diagnosed with ADHD and scored abnormally on the Conners ADHD rating scale. One Williams syndrome study showed that 43% of their study participants had ADHD and most of them were due to inattentiveness, not hyperactivity nor impulsiveness. 

There are only a handful of researchers who have studied ADHD and WS together.  This means that your WS child will most likely baffle a psychologist.  As mentioned before, ADHD as a whole is difficult to treat in anyone because most with ADHD have another condition in conjunction with it.  Most individuals with WS will have learning difficulties, anxiety, ADHD and their unique hyper-social personalities that will make identifying a treatment very difficult for most.

Most kids with WS don't meet every criteria of inattentiveness.  For example, a child with WS that is highly interested in something, such as a tv show, learning about their favorite item or are participating in highly motivating activities, such as music, will stay on task whereas the classic ADHD child will not be able to sit still regardless of the activity.  Also, kids with WS tend to become distracted by specific environmental triggers, such as noise, music, peer conversations, shiny objects and unexpected or novel items introduced to their environment.  Kids with WS tend to have selective attentiveness.  They have trouble maintaining their focus with external distractions that are interesting to them and as a result retain partial information.  Typically kids with ADHD will be inattentive for longer periods of time.  Other differences stem from the WS profile.  While kids with ADHD are often found to have trouble reading people socially, are less able to become empathetic with others.  WS is the exact opposite of this. 

In addition to a slightly different inattentive profile, individuals with WS display different behaviors than other children with ADHD inattentive type.  There are some researchers that argue against labeling WS with ADHD because kids with WS lack aggression that is oppositional to adults.  Kids with WS that act out are often due to anxiety or frustration due to their verbal ability rather than due to hyperactivity. This is just another example of how ADHD is not black and white as far as treatment goes. The combination of inattentiveness, anxiety and the WS behavior profile make diagnosing and treating ADHD very difficult for psychologists.

ADHD treatment for those with WS

There are only 3 studies as of date that studied the effectiveness of medications for ADHD in children with WS, making the treatment difficult for doctors and the families.  The studies also have small sample sizes so further studies are really needed before anyone should suggest one treatment over another.  Treating ADHD has always been very difficult and often require various trials from psychologists.  One study focused on the effectiveness to treat individuals with WS using methylphenidate (MPH), the medication found in Ritalin.  In the study, of 30 children treated, 60% of them improved (3 highly improved and another showed moderate improvement).  This improvement rate is the same as the effectiveness in the general population of ADHD children.  The main side effect was sadness, quiet, and withdrawn behaviors which was shown in 61% of the children taking MPH, so any children showing signs of depression should not be given this medication.  This side effect is much higher in those with WS than in individuals with ADHD alone (8%-22%).

To conclude:

So, in conclusion, there is a lot to learn about WS and the treatment of inattentiveness.  It is important for doctors and educators to work with the children.  Treatment will take time and will require parents to communicate effectively with psychologists so that the proper medications and timing is discovered for your child.  It is also important that schools include modifications and strategies for classroom teachers to use that will help your child maintain better focus in school.  Patience and open communication are essential for treating children with WS and ADHD.

Sources:

• http://www.ncbi.nlm.nih.gov/pubmed/20700845 Abstract of a study that shows the prevalence of ADHD in individuals with WS.
• http://jdc.jefferson.edu/cgi/viewcontent.cgi?article=1003&context=jeffjpsychiatry small psychiatric study that attempted to show that ADHD and anxiety in WS is due to the genetic deletion rather than family inheritance.
• http://books.google.com/books?id=9E9q5112WBgC&pg=PA286&lpg=PA286&dq=adhd+williams+syndrome&source=bl&ots=LdcJeiR7v0&sig=1iiN2afkh91X4siWCceAmkkXO-4&hl=en&sa=X&ei=0M_AT8-mDrKBsgLU9PTzCQ&ved=0CH0Q6AEwBA#v=onepage&q=adhd%20williams%20syndrome&f=false "Understanding williams syndrome behavioral patterns and interventions"
• http://onlinelibrary.wiley.com/doi/10.1002/ajmg.b.31247/full Study about the use of MPH treatments in individuals with WS.
• http://www.ncbi.nlm.nih.gov/pubmed/9203066 Second study about MPH and WS
• http://www.drthomasebrown.com/pdfs/comChapter.pdf A book that summarizes studies on ADHD and explains what trends in research say about the condition.

Visuo-spatial difficulties and how they cause motor delay

You're standing in a field, crouched in position for a fly ball.  Crack!  You hear bat against ball.  Your attention sharpens, your eyes focus on the movement in the air, you run to position your body in its path, hold out your glove, anchor your body to absorb the force, make adjustments in your stance and position as it approaches and you catch it.  All of these actions, although simple to most, are nearly impossible for someone with Williams syndrome.  As mentioned in other sections of this blog, those with Williams syndrome have low tone so their muscle strength and response is slow, but that is only part of the equation of motor delay.  Many of the brain studies that were discussed in the speech section of this blog focus on the spatial difficulties that are prominent in Williams syndrome (WS).  This section of the blog focuses on how this spatial disability inhibits movements in ways separate from low tone.

So, what does visuo-spatial mean?

Many individuals with WS have a hard time interpreting where they are in space.  They also struggle with directional orientation, such as understanding right from left and mirror images.  Visuo-spatial difficulties mean a person would have a hard time judging their surroundings, primarily with visual information, in order to understand where they are in their environment.  For example, imagine yourself navigating down a busy staircase.  It is crowded with people and you must walk in a cramped space.  Now make that stairway spiral and you must move with a swift motion to keep in pace with the crowd.  What do you do?  You may run your finger tips along the stair railing as you move.  You keep your eyes down to the ground to evaluate where you will step.  You tense up the trunk of your body for stability.  All of these actions are your adaptations to that environment.  Your fingertips are gathering information about your position and balance.  Your eyes relay info to your brain about where it is safe to step and your core is in guard to stabilize your body.  These are all visuo-spatial skills. 

People constantly interpret a large amount of sensory information about their environment.  You use peripheral vision, cues from receptors in your muscles about your physical orientation (proprioreceptors), balance information from the inner ear (the vestibular apparatus) and visual cues about what is around you in space.  Those with WS seem to have difficulty coordinating this information.  They struggle when presented with situations where they need to make shifts in their space, such as changing their posture on a crowded bus to let someone walk by.  This body awareness issue along with their difficulties in motor planning, spatial cues and directional cues make it hard for them to do planning activities such as when it is appropriate to cross a busy street or the ability to judge the speed of oncoming traffic.  This is one reason many of them do not drive as an adult (along with anxiety issues- see a future blog post on this topic) 

The directional disability also contributes to reasons why many of the individuals have difficulty understanding left from right, even as an adult and they have some difficulties understanding mirror images.  This directional disability also contributes to handedness.  Most children establish whether they are right handed or left handed by the age of 4-6.  Individuals with WS often don't achieve this until the age range of 5-8.  Many studies suggest this is due to the brain disorganization.  Most with WS will alternate between a preferred hand, use one hand for household tasks, such as eating, and another for writing.  They may alternate the use of their hand when activities require them to cross over the body to complete a task, such as building a large block tower.  Most with WS become left handed. 

There are several theories on why those with WS have this visuo-spatial disability:

• deletion of the LIM-kinase I gene.  There is research out there, although in its infancy, that the deletion of this gene is correlated with the visuo-spatial disability.  However, there are case studies of children missing this gene who do not display spatial delays, so evidence is inconclusive.
• A disconnect in the dorsal stream nervous pathway
• An atypical pattern of brain activity

It all has to do with the cellular pathways in the brain

Many of the researchers in brain studies are psychologists who study the brain function of children and adults with WS.  Their goal is to attempt to identify the areas of the brain that are medically classified as "dysfunctional" or have slower motor pathways.  Before getting into the brain studies, lets take a look at some basic brain anatomy that will help you picture why this "dysfunctional" classification is assigned.

Background on Neural pathways

The human brain is made up of many neurons, or nerve cells.  These cells have cell bodies that are unique in shape and extending from the main portion of the cell are processes or "arms", so to speak.  There are processes, called dendrites, that receive messages.  Sensory neurons sit outside the central nervous system and collect information from the environment using their dendrites.  These sensory neurons have endings called receptors that monitor the environment.  This message containing information about the environment is sent down a long process (or arm) called the axon to a second neuron in the central nervous system.  Neurons in the central nervous system, called association neurons, are located in the brain and spinal cord.  They function to process this sensory information- by interpreting what is happening around you and how the body should react to it.  Then, the association neuron will communicate a new message, send it down its axon to a motor neuron.  The axon releases a chemical (called a neurotransmitter) which travels across a gap and talks to the motor neuron.  This motor neuron then takes that message and tells the muscles how to move.

Inside the brain there are many of these "thinking" neurons.  Depending on where they are in the brain, they have different jobs.  Some areas of the brain receive visual information whereas a separate part receives auditory info, for example.  There are also areas that are for figuring out the sensory info and then a separate area for linking that info to a memory so you can label it or attach it to an emotion.  All of this takes quite a bit of coordination within the brain in order to take in information from multiple senses and combine it to create a scene of what is happening in your environment.

Neurons have jobs

There are special nerve tracts within the center portion of the brain that connect the all the sensory pathways so the brain can share the info.  These pathways are called white matter.  White matter is buried deep inside the brain and is the color white because of tiny cells that wrap themselves around the neurons, called myelin.  The myelin is a fatty layer that allows the message to move quickly down the axon.  It makes for very fast messages and is essentially a "highway" system of neurons that move info from one side of the brain to another. 

  

The outer surface of the brain, which sits around the outside of the white matter is called grey matter.  The grey matter creates what we called the "cerebral cortex".  This is where the "magic" happens.  The cortex is made up of unmyelinated neurons, or neurons that are "naked" without that fatty layer.  The messages are sent more slowly here.  In these regions, your brain decides what to do, problem solves and determines how you will behave.  It is well known that the higher IQ or the better "thinker" you are, the thicker this portion of the brain is.  The grey matter builds up in folds called gyri.  These ridges of the brain are the same on everyone, but they are thicker/thinner based on your genetics and how much you challenge yourself as a learner.  In between the gyri are shallow grooves called sulci. 

In the speech section of this blog, I mentioned that in brain studies, researchers have found that individuals with WS tend to have very thick gyri in areas that are strengths for them- particularly in the auditory region and language centers of the temporal lobe.  There are regions of the brain that have much thinner gyri.  These thinner areas of the occipital (visual) and parietal (sensory) lobes result in a visuo-spatial disability in those with WS.

Figure shows comparisons of gyri in controls (samples from the general public) versus gyri of individuals with WS.  Red areas indicate increases in gyri thickness and blue indicates smaller gyri.  Green shows areas that are comparable between the two groups. 


Streams- flow of information within the highway of the brain

The flow of sensory information that moves through the white matter in the brain can take a variety of different routes.  Two of the more important visual routes are the dorsal stream and the ventral stream. 

There is a section of grey matter in the back of the brain that makes up one gyrus in the parietal lobe.  This gyrus is smaller in the brain of someone with WS than in a typical person.  This section of the brain is involved in the dorsal visual stream.  In the dorsal visual stream, the brain uses visual information to interpret its surroundings, such as an obstacle, and determines how you will move around it.  This stream of information is very slow in an individual with WS due to the small amount of grey matter, making it more difficult for them to navigate.  Research has also shown that in individuals with WS, the brain often doesn't even use this stream when you'd expect it should.  In MRI's this area of the brain shows low activity during movement tasks.

The highlighted area on this picture shows the gyri that is abnormal in WS.  This disrupts the dorsal stream of visual information that is used to produce motor activities.

The ventral stream, in contrast is a strength for those with WS.  It involves information moving from the parietal lobe to the temporal lobe where the gyri are much thicker.  This stream of neural activity is used to recognize people using visual information and labeling.  In case studies, these streams can be tested fairly easily.  If you ask someone with WS to identify the a pathway through an obstacle course they could look at it and tell you where the midpoint of the path is (using the ventral stream) but if you ask them to walk it (which uses their dorsal stream) they would move very slowly and clumsily through the pathway.

Particular motor difficulties that are directly related to deficits in the dorsal stream and are seen in the majority (97%) of individuals with WS include:

• poor dexterity
• slow speed in movements with the arms and legs
• inability to move in response to visual information
• difficulty manipulating an object in the proper orientation to place it in a slot that is shape specific (such as a card in a slot or a block in a shape sorter) 

Problems with nervous pathways are a increasing area of study in WS research.  The nerve interactions between the frontal lobe and parietal lobe point toward behavioral difficulties that are very common in individuals with WS- including high distractability, inability to maintain prolonged attention to a task,  acting impulsively and having difficulty understanding global concepts (topics that are not concrete in thinking).  (Look for a future blog post on ADHD and behavioral profiles of individuals with WS.)


Making plans...

  

Another skill that is inhibited by dorsal stream dysfunction has to do with motor planning.  Motor planning means that the child would see what is in their environment (such as a ball flying at them through the air) have to think of how they want to respond (such as catch it), plan on what muscles need to be used to do so and where that ball will land in space and then relay the message to those muscles to complete the task.  Typically developing children will accomplish this task but many of those with WS often watch the ball as it hits them.  This disability in motor planning- often called apraxia, seems to be a difficulty in about 92% of individuals with WS.  This skill is even more difficult in certain situations such as bouncing the ball because they have to predict what direction it will land.  These tasks that require a person to use a familiar task and modify them to match the spatial information is very difficult for them.

The motor planning dysfunction will often delay their ability to throw and catch a ball.  Although most kids with WS will throw and catch a ball by the age of 6.5, they will likely have a lifelong inability to throw (51%) and catch (67%) in a coordinated fashion.  When throwing a ball, one must rotate their body, move their arm and often step forward with their leg.  Those with WS display an inability to do this at all ages.  They often will throw their arm but lack the body positioning and rotation in the upper body to make a decent throw.  The catching action is mainly due to the visuo-spatial tracking and motor planning required to predict where the ball will land and those skills needed to right the body and extend the arms quickly enough to catch the ball in time.  They simply process this information too slowly and inaccurately in order to accomplish the task.

Studies have shown that although visuo-spatial difficulties are an issue for nearly everyone with WS, there are tools that children can learn to help minimize this disability.  Case studies frequently note that those individuals who learned or utilized verbal cues were better able to navigate obstacle courses.  For example, if the person who is walking through the course studies it first and vocalizes a plan, then as they walk they talk about how to move their body, they move less awkwardly and accomplish the task with better timing.   It is also important to note that individuals that participated in these studies had varying degrees of difficulty.  Some were only slightly impaired in the task and others had higher difficulties with most having a moderate level of challenge.  Therefore, while spatial navigation is a disability for all individuals with WS, the magnitude of that disability lies on a spectrum and can be different for each individual.

Walk this way

Poor motor abilities in an individual with WS extend to many other issues that are rooted in the nervous system.  Individuals with WS, especially in the early years, have a very distinguishable gait, or walk, that is described as clumsy and uncoordinated.  There are a variety of reasons for this.

First, young children who are new to walking have ingrained protective reflexes that they use to maintain balance.  If they find themselves fighting gravity or on an uneven surface, they will right their head over their body, tighten their core and throw their arms outwards to steady their bodies and protect them from a fall.  Kids with WS seem to lack this reflex (I can personally attest that my daughter has fallen many times without ever extending her arms out to catch herself, leading to minor head injuries). 

The majority (between 60-80%) of children with WS have gross motor delays or unorganized motor skills and delays associated with climbing stairs, walking down stairs, running, jumping (especially off an elevated surface), transitioning from one variegated surface to another, walking on uneven terrain (such as grass or mulch/sand), skipping and running.  These delays or motor planning deficiencies are associated with balance issues.  Balance is related to the processing of sensory information by the nervous system.  Approximately 60% of those with WS have balance processing disorders and another 80% have trouble interpreting gravitational signals.


Those with WS have trouble navigating quickly through obstacles that require them to take longer than average strides.  They improve this skill when sensory cues are present such as lights to step in to determine stride length.  But even with sensory cues their walk is much slower than typical.  This indicates there may be some dysfunction within the cerebellum, which is the part of the brain that controls balance and coordination.  Other cerebellar studies have found that in WS, the neocerebellar lobules are enlarged.

  These are regions on the sides of the cerebellum that have major nervous pathways that communicate with the thalamus and the cerebral cortex.  The thalamus is the main area in the center of the brain that associates sensory information with memory.  Major nerve tracts link problem solving to memory to the cerebellum through this nerve tract. 

Scientists have linked this stream directly to motor coordination when learning a new motor skill.  It's used for following a series of steps used to follow a motor procedure, such as riding a bike.  It coordinates limb movements in order to achieve the desired action.  This area of the cerebellum is also heavily linked to an area of the brainstem called the superior colliculi.  This is a visual reflex area that helps coordinate the motor movements in the eyes.  Dysfunction in this can lead to poor muscle control in the eyes and can be another cause of strabismus (see the eyes section of this blog).  The neocerebellar area also helps to coordinate motor movements used to coordinate speech.

Besides brian studies, there are other reasons individuals with WS may have a harder time with motor activities. 

• Tone- The ability for the nervous system to control muscle contractions in appropriate times; previously discussed in this blog (See the muscles section).
• Sleep- sleep is a well known difficulty for up to 97% of individuals with WS which can further affect cognitive development and motor planning.
• Vision- Although vision is not an issue for all children with WS, if a child has strabismis or crossing of the eyes sends conflicting information to the brain about the person's surroundings.  This can lead to increased delay in motor skills- particularly spatial understanding.  This is even more evident if the individual has lost vision in the weaker eye.  This causes the body to lose their depth perception.  Everything will appear flat and in 2 dimensions.  This will cause additional issues with motor development. (see the eye section of this blog)

 

Fine motor delays due to visuo-spatial disabilities

Spatial difficulties offer up difficulties in a variety of motor tasks.  Early in a child's life occupational skills will seem less serious than gross motor skills but as the child ages, their abilities will change and fine motor skills will become increasingly important as they gain independent living skills. 

Self help
Most children (80%) have delays in fine motor skills required for self help.  These can be related to directional disability (used to set a table, for example) but most are due to the visuo-spatial disability.  Through therapy, most of these skills can be mastered, but approximately 30% of adults still find difficulty in some skills such as tying shoes, buttoning clothing, etc. For example, many will have high difficulty using knife skills, such as those used to make a peanut butter sandwich.  They may have trouble grasping the knife, creating the motion to spread the butter, applying the proper amount of force and stabilizing the bread.  This takes motor planning and the ability to judge the environment of the bread and make small motor adjustments to have the proper movement.  Other self help skills such as writing, cooking, buttoning clothing, using a zipper and tying shoes are difficult for a person with WS due to the need to plan motor movements during these activities and have spatial awareness. One study found that, on average there is a 2 year delay in children with WS, aged 4-12, in both fine motor skills and gross motor skills that require visuo-spatial ability.

One major fine motor activity a child with WS will find difficulty in is the ability to manipulate objects in space, such as placing mail into a narrow slot.  This skill is processed by the dorsal stream in the parietal lobe of the cerebrum.  Other examples of difficult motor task include movement planning time.  In one case study, researchers had adults draw a line between two circles using a stylus.  When the shapes changed sizes, those with WS had significantly slower times completing the task.  This study linked difficulties with this task to the inability for those with WS to anticipate the movement of an object and plan their motor response to it.

Drawing

Most typical children will draw recognizable pictures of objects by the age of 5 or 6 whereas those with WS draw them closer to the age of 9 or 10.  This is due to the visuo-spatial delay.  They draw comparably, though, to peers with mental disabilities.  IQ and drawing ability do not match in WS indicating it is an area of disability.  It is also notable to say that they do eventually achieve the ability to do this task by adulthood.

This photo is from the study completed by Dr. Mervis et al. and it shows a drawing of a bicycle, completed by a 12 year old with WS.  All the components of the bike are present, but those with WS have a difficult time picturing how they are connected- a spatial skill.
Therapists have identified a strategy that help individuals with WS improve their ability to draw.  This should be used in OT sessions.  The increase in gains when using the face as a drawing tool stems to brain studies that show individuals with WS use their brain differently to interpret faces.  Typical adults will process facial recognition with the right side of their temporal lobe.  Those with WS use a much larger area of the brain and primarily use the left side of the brain to do this.  The study also had interesting evidence that those with WS use the same amount of processing to interpret the face of a picture of a person that is upright versus on that is flipped up side down.  In typical adults, there is a delay in processing the flipped images as the brain has to try and associate the image with what they'd look like right side up.  Those with WS use more brain activity looking at a face in any position than a typical person would and they use the same brain activity despite the picture orientation.


Ways to help improve their drawing skill is to allow them to draw motivating pictures- focus on drawing people, facial expressions, etc rather than shapes.  Kids showed greater gains when they had developmental interpretation therapy session to help them process how the picture should fit together.  They also improved with frequent practice.  Case studies show that in children, ages 4-6, who participate in the developmental interpretation sessions and practiced drawing people and houses showed significant gains in elaboration of the picture, increases in inclusion of objects, improved their ability to draw an object in its proper context (like a person in a house) and increased in the ability to combine features (all the parts of the picture connected in the proper ways such as heads were on necks and legs attached to bodies).  Improvement has also been shown to have the subject verbally express what they are drawing and how it should connect the lines.  When they talk through the process, the picture ends up more organized.

In the same study the kids were assessed again between the ages of 12-15.  After 6 years of growth, the ability to draw more organized pictures improved in all subjects of the study.  So, although the skill is delayed, it does improve with time.  In all age groups, the subjects were able to draw more organized pictures of people and flowers versus objects such as houses, bikes and animals. 

In conclusion

Visuo-spatial difficulties are an issue for all individuals with WS but with purposeful and educated therapists, there are skills and techniques that they can learn to help them overcome this obstacle and improve their self help and motor skills as they age.

Sources:

• http://www.nature.com/nrn/journal/v7/n5/full/nrn1906.html Primary source on brain studies linked to WS
• http://www.psych-it.com.au/Psychlopedia/article.asp?id=412 A summary of psychatric studies related to brain and behaviors in WS.
• http://www.dartmouth.edu/~rswenson/NeuroSci/chapter_8B.html Information on cerebellum function
• http://www.n-acetylaspartate.com/ Information on  the neurotransmitter, N-acetylaspartate
• Neurobiological models of visiospatial cognition in children with williams syndrome
• http://www.springerlink.com/content/p57121g83734300g/
• http://www.physio-pedia.com/index.php/William's_Syndrome#cite_note-Seventeen-16 An overview of Williams syndrome manifestations related to physio-motor intervention
• http://books.google.com/books?id=9E9q5112WBgC&pg=PA136&lpg=PA136&dq=motor+delay+williams+syndrome&source=bl&ots=LdcBfjN6p1&sig=4uSFQrsE1J7LibATNjKYZnFb6I8&hl=en&sa=X&ei=QVtIT62ACJD_sQLj_anNCg&ved=0CCkQ6AEwATgK#v=onepage&q=motor%20delay%20williams%20syndrome&f=false A google sampling from the book "Understanding Williams Syndrome"- used the sections of motor delay