Serene Forest

Tuesday, December 10, 2013

What is Andersen-Tawil Syndrome?


Hello All,

I have been diagnosed with the most rare form of Periodic Paralysis called  Andersen-Tawil Syndrome. I was diagnosed based on my symptoms and characteristics. This is called a "clinical diagnosis."
Andersen-Tawil Syndrome (ATS), given a name in 1971 was the first ion channelopathy discovered. It is very rare form of Periodic Paralysis, a mineral metabolic disorder. ATS is an autosomal dominant disorder, which means it is usually passed by one parent to the child. If someone is a carrier his or her children have a 50% chance of being born with it or as a carrier. ATS accounts for approximately 10% of all periodic paralysis cases. It is characterized by three particular components: periods of paralysis
from high, low or normal potassium levels, distinctive craniofacial and skeletal characteristics and long QT interval heartbeat with a predisposition toward life-threatening ventricular arrhythmia. However, affected individuals may express only one or two of the three components and they may be very subtle.
Some of these components and symptoms were found in my mother, possibly through her father, and many of her descendants; specifically, two of her three sons and me, her only daughter. Many of her grandchildren and great grandchildren also have varying degrees of the characteristics and symptoms. 
 Some of the manifestations of this condition are serious and life threatening. Each family member of someone diagnosed with ATS should be well educated about this syndrome, in particular, regarding the episodes of paralysis (full body or partial), the heart complications, the strange effects of most medications and the serious complications of anesthesia.

An individual is born with Andersen-Tawil Syndrome and symptoms may begin in early childhood or not until later in life. Members of the same family can have varying degrees of it or some of the characteristics without actually having it.

During an attack, brought on by many triggers to include: carbohydrates, sugar, medications, exercise, heat, cold, periods of sitting too long, stress (good or bad), etc; potassium leaves the organs it belongs in and goes into the muscles where it does not belong and paralyzes the muscles (totally or partially). The depletion of the potassium in the other organs can cause symptoms such as irregular heartbeat, weakness, fainting, numbness, tingling, breathing issues, choking/swallowing problems, exercise intolerance, etc. After many years the body can become permanently weakened.

It is important to get a diagnosis for proper treatment to avoid the permanent disabilities. It is also important so one can avoid the triggers and hopefully control the episodes as much as possible. Most over-the-counter medication, as well as those prescribed by physicians, such as antibiotics and painkillers can cause serious consequences.  Many medications can cause an opposite effect such as sleeping aids can keep you awake and agitated.

Executive Functioning (EF) Disorder can accompany ATS. There are three primary layers of executive functions: self-regulation, organization and high order reasoning skills. It is associated with many disabilities: Attention Deficit Hyperactivity Disorder (AD/HD), Learning Disabilities (LD), Tourette Syndrome (TS), Obsessive Compulsive Disorder (OCD), Autism, Depression, Bipolar, etc. It is important to have these conditions diagnosed as early as possible for proper treatment, training, and education.
To better explain and describe ATS I am including the following information I have collected over my years of research for the "Characteristics of Andersen-Tawil Syndrome." There are more than the 5 or 6 we typically read. Several articles are sighted for this section due to the differences in symptoms in some of them. Some personal information has been added for clarity.
Symptoms & Characteristics
Several articles are sighted in the following section due to the differences in symptoms in some of them. Some personal information has been added for clarity.

Anderson-Tawil syndrome is a disorder that causes episodes of muscle weakness (periodic paralysis), changes in heart rhythm (arrhythmia), and developmental abnormalities. The most common changes affecting the heart are ventricular arrhythmia, which is a disruption in the rhythm of the heart's lower chambers, and long QT syndrome. Long QT syndrome, is a cardiac channelopathy, which causes the heart (cardiac) muscle to take longer than usual to recharge between beats. If untreated, the irregular heartbeats can lead to discomfort, fainting (syncope), or cardiac arrest.
 
At this time, there are two recognized types of Andersen-Tawil syndrome, Type 1 and Type 2, which are distinguished only by their genetic causes. One has a known genetic mutation and the other, though the symptoms and characteristics are exactly the same, has no known genetic mutation, which has been discovered.

Physical abnormalities associated with Andersen-Tawil syndrome typically affect the head, face, and limbs. These features often include a very small lower jaw (micrognathia), dental abnormalities, low-set ears, widely spaced eyes, and unusual curving of the fingers or toes (clinodactyly). Some affected people also have short stature and an abnormal curvature of the spine (scoliosis).
 
Symptoms

·Widely spaced eyes
· Short stature
· Scoliosis
· Webbed toes or fingers
· Unusual short fingers
· Low set ears
· Broad forehead
· Small jaw
· Protruding jaw
· Broad nasal root
http://en.wikipedia.org/wiki/Andersen–Tawil_syndrome

Disease characteristics.

Andersen-Tawil syndrome (referred to as ATS in this entry) is characterized by a triad of episodic flaccid muscle weakness (i.e., periodic paralysis), ventricular arrhythmias and prolonged QT interval, and anomalies such as low-set ears, ocular hypertelorism, small mandible, fifth-digit clinodactyly, syndactyly, short stature, and scoliosis. Affected individuals present in the first or second decade with either cardiac symptoms (palpitations and/or syncope) or weakness that occurs spontaneously following prolonged rest or following rest after exertion. Mild permanent weakness is common. Mild learning difficulties and a distinct neurocognitive phenotype (i.e., deficits in executive function and abstract reasoning) have been described.
www.ncbi.nlm.nih.gov/pubmed/20301441


Executive Functioning (EF) Disorder

Relates to difficulty in self regulation, organizing, integration, or high order reasoning skills.

"Executive Function disorder, is a disability of not being able to show what you know"

Executive Function disorder is associated with many disabilities: Attention Deficit Hyperactivity Disorder (AD/HD), Learning Disabilities (LD), Tourette Syndrome (TS) , Obsessive Compulsive Disorder (OCD), Autism, Depression, Bipolar, etc.

Most people with AD/HD also have Executive Function Disorder, but someone can have Executive Function Disorder without being diagnosed with a disability. Executive Function program and services would be needed if the student progress in the general growth in the acquisition of knowledge and skills are being negatively impacted.

Eight Pillars of Executive Control
 by Dr. Adam J. Cox, Ph.D., January 2009,
Minuteman Technical High School SEPAC presentation

1. Initiating Action being able to organize one’s thoughts well enough to get started on a particular task without having to be asked multiple times.
2. Flexible Thinking involves learning to adapt by shifting one’s focus and pace as various situations unfold. Imagine how difficult it would be to drive your car if it wouldn’t turn and only went one speed. (About as difficult as parenting a child with only one speed and one direction!)
3. Sustaining Attention focusing long enough and accurately enough to learn important information. By extension, attention also involves the ability to block distraction. A well-orchestrated “executive brain” knows its priorities.
4. Organization is about managing space. It’s also about taking the emotional impact of chaos seriously. Why? Because chronic disorganization undermines forward momentum – a sense of accomplishment.
5. Planning is about managing time, and is more important than any other executive pillar when it comes to finishing things on schedule. A planning mind uses time as a tool to clarify priorities and enhance productivity; indispensable skills to 21st century success, beginning with school and, eventually, careers.
6. Working Memory is the ability to retain information long enough for it to be stored in long-term memory. Our society has a word for this process – learning. Of all the executive controls, working memory is the most pervasive, contributing to the smooth operation of every pillar. (Working memory is the rocket fuel of the modern mind.)
7. Self-Awareness pertains to having both sufficient self-knowledge and an ability to perceive how others see you. This information is essential to making purposeful choices about how to act in situations where one wants to avoid unintended consequences that lead to isolation or ostracism.
8. Regulating Emotions means expressing one’s feelings in proportion to the events that elicited them. When a child under or over-reacts, she is out-of-sync with people or particular events. Socially, people tend to ignore a silent recluse, and run away from an “erupting volcano.”
From his book: No Mind Left Behind: Understanding and Fostering Executive Control- The Eight Essential Brain Skills every Child Needs to Thrive, by Adam J. Cox, Ph.D. Psychologist
Executive Function Skills, by Sarah Ward, MS, CCC-SLP, February, 2007 SPED PAC Presentation

3 Primary Layers of Executive Functions:

1.      Self-Regulation
a.      Awareness
b.      Motivation
c.       Initiation
d.      Emotional Control
2.      Self-awareness
a.     Self monitor the ability to inhibit or delay responding, which permits impulse control resistance to distraction and delay of gratification)
b.      Metacognition (Learning how to learn)
3.      Organization and Integration
a.      Integrate details into a bigger picture
b.     Organize and store information so it can be traced back and retrieved over time (Episodic Memory), (used for planning for the future)
4.      Higher Order Reasoning Skills
a.     Analyze
b.     Draw a conclusion
c.      Solve a problem
d.     Predict an outcome
e.     Reason
f.        Evaluate
http://concordspedpac.org/ExecutiveFunctions.html

Symptoms of Andersen-Tawil Syndrome
 
· Ventricular arrhythmia
· Abnormal heart rhythm
· Long QT syndrome increased time needed for heart to recharge after each heart beat
· Irregular heartbeat
· Discomfort
· Fainting caused by irregular heart beat
· Small lower jaw
· Dental abnormalities
· Low-set ears
· Widely spaced eyes
· Abnormal curving of fingers
· Abnormal curving of toes
· Short stature
· Abnormal curvature of the spine
http://www.wrongdiagnosis.com/a/andersen_tawil_syndrome/symptoms.htm

Distinctive physical features recognized initially included low-set ears, ocular hypertelorism, small mandible, fifth-digit clinodactyly, syndactyly, short stature, broad nasal root, and scoliosis [Andersen et al 1971, Tristani-Firouzi et al 2002, Donaldson et al 2003]. Dental enamel discoloration was noted in two kindreds with the Gly300Asp and Arg218Trp mutations [Davies et al 2005].
Detailed, prospectively collected data in ten individuals with confirmed KCNJ2 mutations have expanded the phenotype to include a characteristic facies and dental and skeletal anomalies [Yoon et al 2006a].
· Characteristic facies include broad forehead, short palpebral fissures, full nasal bridge with bulbous tip, hypoplasia of maxilla and mandible, thin upper lip, and a triangular shape.
· Dental findings include (among others) persistent primary dentition, multiple missing teeth (oligodontia), and dental crowding.
· Skeletal findings include mild syndactyly of toes 2 and 3 as well as fifth-digit clinodactyly.
· Novel findings include small hands and feet (<10th centile for age) and joint laxity.
Isolated reports of renal anomalies include unilateral hypoplastic kidney [Andelfinger et al 2002] and renal tubular defect [Davies et al 2005].
http://www.ncbi.nlm.nih.gov/books/NBK1264/

Dysmorphic Features:

May be very subtle, partial or seen in 'unaffected' family members
Skeletal:
· short stature (often);
· scoliosis

Hands/Feet:
· tapering fingers,
· clinodactyly (inward curvature/ 5th fingers);
· brachydactyly (unusually short fingers);
· syndactyly (webbing between fingers or between 2nd and 3rd toes)

 
Facial:
· hypertelorism (widely spaced eyes);
· mandibular hypoplasia (small jaw);
· low-set ears;
· broad forehead;
· malar hypoplasia; (underdevelopment of cheekbones)
· broad nasal root;
· micrognathia (short jaw);
· prognathism (protruding jaw);
· ptosis; (an abnormally low position (drooping) of the upper eyelid)
· cleft palate, high arched palate

Definition of Terms for Symptoms:

· characteristic facies (characteristic appearance of the face in association with a disease or abnormality)
· brachydactyly (unusually short fingers)
· brachydactyly type D (clubbed thumbs) (characterized by a slightly shorter thumb that is round in section and larger at the end)
· clinodactyly (inward curvature/ 5th fingers);
· syndactyly (webbing between fingers or between 2nd and 3rd toes)
· small mandible (lower jaw in which the lower teeth reside and chin)
· hypoplasia of maxilla (small upper jaw)
· short palpebral fissures (short opening for the eyes between the eyelids)
· persistent primary dentition (still have some baby teeth)
· ocular hypertelorism (widely spaced eyes);
· scoliosis (curved spine)
· microcephaly (abnormal smallness of the head)
· delayed bone age (slowed degree of maturation of child's bones)
· joint laxity (loseness of the muscles and soft tissue surrounding a joint)
· broad nasal root (wde space between the inner corners of eyes)
· broad forehead (increased distance between the two sides of the forehead or top to bottom of forehead)
· malar hypoplasia (small cheek bones)
· micrognathia (short jaw);
· prognathism (protruding jaw)
· ptosis (an abnormally low position (drooping) of the upper eyelid)
· cleft palate (a congenital fissure in the roof of the mouth)
· high arched palate (roof of the mouth is high)

Facial Dysmorphology

Drawings are used to depict terminology and to illustrate certain aspects of facial variation.
http://www.peds.ufl.edu/divisions/genetics/teaching/facial_dysmorphology.htm


In most of the textbook or journal articles, Andersen-Tawil Syndrome is described as being so rare that only 100 cases have been diagnosed worldwide. This is incorrect. In a part of France alone, over 90 cases exist. 100 cases of ATS is a gross underestimation. Far more cases exist in varying forms.


Until later...

3 comments:

  1. Susan could you share with us which portion of France has 90 diagnosed ats cases? This is for me to compare with some of my genealogical information.. also I would love to see the article or written source for this information.. I wonder why it takes so long for the scientists doing studies to update this information.. they take such care in doing their studies it seems like they could take time to update information on how common these conditions are becoming.. kcb

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  2. I made a mistake on my numbers...my memory was off....I apologize...after finding the article.....however, the actual statistics were 36 woman, from 20 different families, from only 9 hospitals in France and who were diagnosed as carriers of KCNJ2 mutation, took part in the study. That is still 36 of 100. I imagine that each of those woman had family members with it also...parents and children .....so that would bring it up to at least 72 if there is at least one child per family and add the parent that passed it to them...that would be at least 108 cases!!!!!! That would be the least amount among those women.

    "We conducted a retrospective multicentre study in nine French hospitals. Patients were recruited only if they were KCNJ2 mutation carriers. Thirty-six patients (female n = 22, 61%) from 20 unrelated kindred ..."

    http://europace.oxfordjournals.org/content/early/2013/07/17/europace.eut160.abstract

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  3. Jacqueline OppermanApril 18, 2017 at 5:01 PM

    Hi my name is Jackie and I was diagnosed with ATS when I was 36 years old. I have a medical history of years of weakness and syncope episodes that no one knew why. No one belived me after so many years that it was in my head or I was looking for attention or I was dehydrated. I hate this disease! Since I was in puberty till now I still get it. When I was young I would get this every month and would last for weeks. My brother would have to pick me up because I was so weak I couldn't walk or stand. I also have long QT syndrome I have had syncope episodes through out my teens and adult life, until I was 36 I had an syncope episode which led me to getting my first ICD because my heart stopped. I have had 5 ICDs since I'm now 51. I've never been officially diagnosed. The drs. just suggested it. I have some of the characteristics of ATS I am short. My brothers and sisters are 6 ft I'm 5'2". My dentist says I have teeth missing and some odd shaped teeth not sure about eyes and ears. My feet are slightly webbed at the bottom. I did have genetic testing done however at the time they had no idea what to look for. I see now they have a specific mutation to look for. I have looked somewhat to see if they have any research going on for this but have not found anything yet. My whole life was like why me! Why am I the only one! But now I can see that I am not alone anymore. That makes me feel better. I just had the stomach flu with full on vomiting and diarrhea. That was 2 days ago. I thought I would be recovered by now however I have a feeling that my body electrolytes are off and my muscle weakness is due to my ATS kicking in. I will need to go in to the doc and have my blood drawn to see what levels everything is at. It's really hard to explain this to my employer that I will be missing 3 or more days of work. Thank you for having your blog. There are so many missing years of sports, of dances, moments with my children, worry that my family and myself have lost over the years. I hope they can come up with a permanent cure or to get rid of the mutation so no one else has to go through this. Thanks again.

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