Phelan-McDermid Syndrome Primer

I first heard about Phelan-McDermid Syndrome (also called PMS, but not to be confused with the female monthly cycle issues) after reading this recent blog post on Autism Speaks. PMS is related to autism due to behavioral symptoms (poor eye contact, social anxiety, and perseverative actions) but some question whether the genetic deletion is a cause of autism or if it separates these individuals from other spectrum disorders. Because many of the symptoms overlap, children with PMS may be diagnosed with autism or ADHD or dystonic CP or some combination of these unless a specific genetic test is performed.

PMS is cause by the absence or loss of genes at the tip of Chromosome 22 (a 22q13 deletion). The loss of Shank3/ProSAP2 gene is suspected to be the primary cause of the symptoms associated with PMS. The Shank3 gene plays a role in the formation of the nervous system during fetal development. As in many spectrum disorders, invididuals with PMS may have mild or more severe challenges in several areas, including:

• delayed or absent speech and communication
• low muscle tone (hypotonia) - delayed sitting up, rolling over, crawling, walking
• challenges with eating (sometimes beginning with bottle/breast feeding as a newborn)
• sleep disturbances
• emotional instability

There are also some physical characteristics that may be present:

• may be tall for their age
• subtle facial features: long head shape, puffiness around the eyes, long eyelashes, droopy eyelids, puffy cheeks, large ears
• large fleshy hands, underdeveloped toenails, lack of perspiration - easily overheat.

Both the autism speaks blog above and an article at the Phelan-McDermind Syndrome Foundation website note that as individuals with PMS get older and more skills are expected they fall further behind and their challenges become more apparent. There is also some evidence that individuals with PMS may lose one skill while they make progress in another area.

PMS and Fragile X Syndrome both present strong arguments for the benefits of genetic testing - basically to receive a more specific diagnosis that will allow more focused efforts in intervention, support, and treatment. Some of the comments from the autism speaks blog article seemed to imply that this level of specificity is not necessary if the child is "accepted" and supported in their education and development. What do you think about these issues? We have not pursued any genetic testing for our daughter (yet) mostly due to financial considerations and insurance concerns. Certian phrases in this article made me wonder if we should, though. For instance similar to the little girl highlighted by Autism Speaks, several people have noted that our daughter is "too social" to be autistic, though that is her official diagnosis. I maintain that though she enjoys being with people she does not understand social constructs...her desire to be with people is a great motivator for helping her learn some of the obvious rules of social behavior, but some of the more subtle interactions still seem to be beyond her reach. I am more curious than ever whether we should consider genetic testing and whether it would clear up some of the mysteries we continue to face, but given our excellent progress to date I wonder how much we would gain. I welcome your input...just click on comments below.

If you are interested in learning more about Pheland-McDermid Syndrome I suggest you begin here.

Fragile X Syndrome

Over the last year or so I've written some short pieces about Fragile X Syndrome, but I've never written a primer about it. It is timely to do so now for a couple of reasons. First, a group of Fragile X advocates - parents, doctors, therapists and researchers - recently completed an annual trip to Washington, D.C. to meet with various congressional leaders to encourage them to increase funding for research into Fragile X Syndrome, and to sponsor legislation to benefit individuals with Fragile X and other special needs. Second, in just a few short days Autism Awareness Month (April) will begin.

Are you aware that for 2-6% of all individuals diagnosed with autism, the Fragile X gene mutation is the cause? That may not sound like much, but it is the largest known, single-gene mutation cause of autism. You can learn more about the distinction between the two disorders and the link between them by reading here. Suffice it to say that anyone diagnosed with autism should be tested for the Fragile X mutation and that any strides toward understanding and treating Fragile X may help us learn more about autism, too.

Fragile X is also the most common inherited form of cognitive disability. It begins as a mutation on a gene (FMR1) found on the X chromosome. This mutation affects the structure of the X-chromosome such that under magnification it actually looks "broken", hence the name of the disorder. The FMR1 gene is responsible for instructing cells how to make the protein FMRP. The role of FMRP is not known, but clearly has some role in brain development. In the simplest scenario, because FMR1 is located on the X-chromosome, Fragile-X is carried by females. Since females have two X-chromosomes one can still generate FMRP if the other bears the FMR1 mutation; they have the mutation, but not the disorder. Males with a fragile X cannot make FMRP and will develop the characteristics of Fragile X Syndrome. However, both males and females can be carriers and both males and females can have Fragile X, so it's complicated.

In addition to behavioral characteristics that are similar to autism (language delays, motor delays, sensory disorder, poor eye contact, etc.) often individuals with Fragile X have some physical characteristics in common (large ears, long face, soft skin, flexible joints, and flat feet). Usually there are cognitive issues ranging from mild learning differences to severe cognitive disabilities.

To learn more about Fragile X, I recommend starting at the National Fragile X Foundation website. In particular, this video, which I have linked to before is very powerful.

Using Someone with Skin On

After two weeks off I'm trying to jump back in with both feet by linking up with the blog carnival over at (in)courage. I may have missed the cutoff since I generally write so late in the day. I'd still "(in)courage" you to check them out. It is a sweet site. More on them later, probably.

Our assignment for the blog carnival is to write about someone who encourages us, specifically someone in Christian ministry. My usual post for the day is a Bible theme related to Special Needs, so let's see if I can make this all come together.

I would like to honor our most recent Pastor at the church we attend. He would die a thousand deaths if he knew I was typing this right now, so I will not mention his name, but many of you know who I'm talking about. I may not have shared as openly before how much he has encouraged me, though. Many of you are already fans, and I hope my own story will make yours that much sweeter.

This Pastor is the one who performed our wedding ceremony, instructing my husband to treat me as fine china in spite of my strong personality and personal achievements. He is the one who encouraged me to pursue every avenue of treatment when my anxiety disorder threatened our first year of marriage, medication and Biblical counseling included. He dedicated our oldest daughter to the Lord in those early days when we thought she was just a feisty and independent little so-and-so. He helped us with remodeling projects. He came over the day that my husband lost his job and brought muffins. He visited me in the hospital when I was on bed rest for six weeks while expecting our twins. He and his wife came over shortly after the twins were born and loved on them while I got dinner ready. When we first started to understand our daughter's challenges more they were there with wisdom, advice, more babysitting, and coming to IEPs. They helped us understand "the system" and what was happening with our daughter. Several months later when I was at my wit's end he sat with me on Christmas Eve, of all days, and gave me several scriptures and lots of advice, and most of all prayer. He joined me in praying that God would provide "a way out" of the anger, frustration, and outright fatigue that I was experiencing. Just a couple of weeks later God did provide the beginning of the way out. In short, at every major turning point for almost ten years now my Pastor has been Jesus with skin on to me.

You may be wondering how a Pastor would know much about IEPs and the school system. He is also the father of a young man who has Fragile X Syndrome and autism. He has allowed God to use his son's challenges to teach him, and our whole church family, so much. He has poured himself out for our church and for his family. A couple of weeks ago he gave his last sermon at our church. The demands of caring for his son have been overwhelming for years now, and he felt God leading him to move out of active ministry and care for himself and his family. I would ask you all to pray for them as they face many changes now and in the near future. Pray God's provision, and that the Church will show up for them as they have so often for others.

One of my favorite scriptures that my Pastor and his wife have both shared with me to encourage me is

Isaiah 40:11 - He tends his flock like a shepherd: He gathers the lambs in his arms and carries them close to his heart; he gently leads those that have young. (NIV)

God cares for our little ones so much. They are close to His heart. And He is gently leading us, too. Sometimes He uses someone with skin on to lead us...thanks be to God!

Adrenoleukodystrophy (ALD)

My apologies for posting this late. I am battling off a head cold and sleep was more imperative than blogging last night.

Following up on Wednesday's review of Lorenzo's Oil, I thought you might like to know more about the debilitating metabolic disorder affecting the centerpiece of the movie, Lorenzo Michael Murphy Odone.

Adrenoleukodystrophy (ALD) is one of several diseases called leukodystrophies. ALD is an X-linked genetic disorder, and is very rare (1:42000). This means that a woman (xX) has a mutated X chromosome that can be passed on to both daughters and sons with a 50/50 chance each time that they will inherit the mutation. If a daughter (xX) inherits the mutation she most likely has a healthy X chromosome that can compensate for the mutated gene. Some women may have mild symptoms of these disorders but otherwise remain "carriers" in the gene pool. When a son (xY) inherits the mutation, he will have the disorder. [Duchenne Muscular Dystrophy (DMD) and Fragile X Syndrome (FX) have similar inheritance patterns...interesting] This point comes up during Lorenzo's Oil as Lorenzo's mother, Michaela, struggles with the knowledge that her DNA is the root cause of her son's debilitating disease. (More on this Tuesday...)

Perhaps the most devastating aspect of ALD is that symptoms do not manifest until a boy with the disorder reaches the age of 4-10. Until the symptoms appear every aspect of the boy's development will appear typical. At the outset of the disorder behavioral issues may begin to surface - tantrums, sensory disorder, followed by a decrease in visual, auditory, motor and oral functions. Gradually various bodily functions shut down until death occurs, usually within 10 years of the onset of symptoms.

The gene responsible for this mayhem was identified in 1993 (just after the movie came out). It encodes a "transporter protein" that is responsible for moving an enzyme around. Think of this transporter as the bus that the enzyme takes to work. If the bus breaks down the enzyme can't work. The enzyme is responsible for breaking down long chain fatty acids normally found in our diet. If the enzyme can't get to work the long chain fatty acids build up in the bloodstream. Somehow (no one quite knows how) these excess fatty acids then cause damage to the myelin sheath that surrounds the nervous system. Without myelin nerve cells cannot properly conduct the signals that keep all of our systems working.

The movie, Lorenzo's Oil, is about Lorenzo's parents working alongside and sometimes around the medical community to develop an experimental treatment for ALD. Lorenzo's Oil is actually a mixture of two very specific oils (they are components of olive and rape seed oils in the movie) that, together with a diet low in very long chain fatty acids, helps to lower and keep the level of long chain fatty acids low in the blood serum. A large scale clinical trial is underway to investigate the efficacy of this treatment. It seems particularly effective in cases where the patient is asymptomatic or has mild symptoms. If myelin damage has already occurred there is currently no method to repair that damage. Some other potential treatments include bone marrow transplant, stem cell transplants from cord blood, and some drug trials are underway.

You can read more about ALD, Lorenzo Michael Murphy Odone, and myelin here:

• ALD
• Lorenzo Odone
• Myelin Project

Sunday Digest 15

1) In doing some research for some friends I found out that the Special Education Rights and Responsibilities (2005) publication of Protection and Advocacy, Inc. Is available on-line here. Unfortunately there isn't a newer version, and a lot of important changes happened in 2005. However, the first chapter, which gives an overview of special education law, has been annotated to reflect those changes. This resource puts parental rights and responsibilities into plain English, and presents the material in a question/answer format that I find very helpful when I'm looking for one specific bit of information.

2) Another resource for IEP meetings...another reason to consider getting an iPhone? This is an iPhone app that is supposed to help both parents and teachers store information and make sure that a student's IEP meets federal requirements. I do not own an iPhone, so I can't say whether this is useful or not. It sounds good. If you have an iPhone and want to try it out and let me know...

3) This video is a good explanation of Fragile X Syndrome. Fragile X is the only KNOWN cause of autism. A group of parents and professionals caring for individuals affected by Fragile X were in Washington, D.C. this past week advocating for all families with special needs. Because of the link between Fragile X and autism, any basic research that advances diagnosis or treatment of Fragile X could potentially yield progress in the same direction for autism. Learn more from the video or from fragileX.org.

4) I recently saw two articles about Kristi Yamaguchi in different magazines. Still caught up in the Olympic spirit (I still have approximately 35 hours recorded on our DVR to watch) I read both articles with increased respect for this icon of figure skating. Now that she has retired from competitive skating she has started a foundation called Always Dream. At least one focus of the organization is to encourage and support children with special needs. They opened an accessible playground in Fremont, CA in January 2010. After reading the first article I was curious about how Ms. Yamaguchi developed this passion. The second article explained that when she was born Ms. Yamaguchi had club feet. Several operations and years of therapy later you'd never know it from watching her skate!

5) I am fascinated by Temple Grandin. There was recently a documentary on HBO about her life. In case you are not familiar, she was diagnosed with autism at age 2.5 years (1950s era) and is now a professor of animal science. She has written a couple of books about her experiences. I reviewed her book Emergence several months ago. Today on twitter I found this video of Dr. Grandin lecturing on autism. It is over an hour long. I haven't watched the whole thing, but the part I have watched so far has been very informative, interesting, and entertaining even! I think we have a lot to learn from her...