Subject: genetics

hi everyone, i have been unable to get through all my mail lately since all the kids are home on summer vacation. i wanted to tell you about our last visit with the geneticist and her counselor. while they agreed that jessica(2 1/2) has some features of A.S. they are also testing her for another synd. it is called SMITH-MAGENIS synd. the odd thing is ,it is alot like A.S. children with S.M.S. present with severe sleep disturbances, hypotonia,ataxic gate(the same walk as A.S.) feeding difficulties in infancy, hyperactivity, happy and friendly disposition, affectionate and love to give hugs to others and themselves.also with this synd. there are alot of behavioral problems such as putting foreign objects into body orifices,picking at skin or sores also some children have been known to pull off their fingernails and toenails.(that one made me shudder) also some children have a decreased sence of pain and their receptive language is better than expressive. these children have alot of ear infections and this may result in some hearing loss.also some have strabismus,myopia,mild congenital heart disease or a murmer.also a few have renal anomalies and mild to moderate scoliosis and seizures. the preceding was from papers that the geneticist gave us. she also told us that the children have short fingers and toes .they are going to look for a deleation on chrom. 17p they told us it would not be seen during a regular check of the chrom. unless you were looking for this intentionaly. they use a fish study to check.well got to go, thanks for listening,

michele meixell

Subject: Re: genetics

Hi Everyone, After reading Michele's post on Smith-Magenis Syndrome I did a quick net search for more information. My daughter Devin (3, AS?) has normal genetic studies and some of the clinical features of AS so hearing about another chromosomal disorder similar to AS sent me into search mode. In addition to what Michele stated about SMS my quick search revealed that children with SMS tend to have dymorphic facial features (brachycephaly, midface hypoplasia, prominent forehead, epicanthal folds, broad nasal bridge, and short stature). They have varying degrees of mental retardation but tend to fall into the moderately affected range (IQ in the 50s). Like children with AS they also have better receptive language but in general most do develop expressive language. The mystery of AS children with normal genetic studies continues... Continuing on this topic, didn't Dr. Williams present a paper on the deletion negative, normal genetic studies AS child at the conference (or is my brain in overload again!!)? I'd be really interested to hear what he said if anyone has information. BTW, Devin is my first child (no miscarriages). My mother also smoked during her pregnany. And Devin loves to be nose to screen with the TV! She does her best pulling up using the TV (I keep doing the scales of pulling up-eyesight, pulling up-eyesight...). I thought I'd throw this out for whatever it may be worth... Devin suffered from chronic ear infections for most of her life (started at about 6 months). Two weeks ago she had tubes placed. I haven't noticed a huge difference in her hearing (an earlier hearing test revealed that due to middle ear fluid she heard at 50 decibles - like being underwater all the time) but her mood (knock wood, formica, plastic, whatever) has changed dramatically. For the past two weeks she had been the happiest I have ever seen her. I only wish we'd done them sooner. The procedure was a breeze. By evening you would never had known she spent the morning in the hospital! I know ear infections are common in all children but I wonder if the incidence is higher with AS? Finally, about a month ago I sent my dues for ASF membership along with an order for 3 videotapes. I still haven't received anything. Does anyone know if it usually take awhile for membership/videotape orders to be processed?

Warm regards, Kelly

Subject: re: genetics

Is Smith-Magenis syndrome named after Dr. Ellen Magenis? She is a geneticist here in Portland Or and the person who initially diagnosed Kyra clinically with AS at 13 months old and then confirmed to be deletion + 13 years later when the technology was better. She's a very sweet and knowledgeable person. - jane

Subject: Re: re: genetics

jane, hello, the paperwork i have on S.M.S.. lists the founders as dr. ellen magenis and ann c.m. smith . it says that dr. magenis is a cytogeneticist and dr. smith is a genetic counselor. take care,

michele meixell

Subject: RE: genetics

Hi Michelle,

re: the Smith Magenis Syndrome, I received a call from a mom in Lee's Summitt MO, the other night. She has a 10 year old son and was on the path to ANgelmans FROM THE OPRAH SHOW ! (I know there was a campaign on to get to OPRAH, did someone succeed ?) I would very much like to put her in touch with someone closer to her Missouri region, Is anyone online from MO that would like to contact her to chat? I was not really to encouraged when I heard her say that her son was VERY VOCAL, walked at 14 mos and wasn't too magnetized to water or plastic. Please let me know if you have information on the speach characteristics from the S-M Syndrome? I also believe her son had no real history of Seizure, but night terrrors were evident. She also indicated her son had the early feeding problems, (poor sucking), was very affectionate and happy. I have encouraged her to subscribe, (via her sister's PC) If you or anyone can provide more data , It would be greatly appreciated !

Thanks ! Joe

Subject: Genetics

I was just at my appointment with the geneticist in which I spesificly asked her how this deletion happened and when. I was then told that it was when I was concieved and my eggs were developed that the deletion was there. She said it had nothing to do with me and my husband or anything past me being conccieved for that matter.

Corinne

Subject: Re: Genetics

Corinne, Thank you for sharing this info! This makes me feel a lot better. I always wondered where my defect, that caused Jennie's AS, came from and what I might have done to cause it.

Janice Daley (Jennie 15+)

Subject: Genetics

Here I am sticking my oar in again. Re: genetics, if anyone is interested in our story.

I was 38 when Sara was born, and I had amniocentesis because of "advanced maternal age" (flattering) which showed a Robertsonian translocation. That means, if I recall correctly, that one of Sara's 15 was paired with one of her 13 and vice versa. There was no material missing, and we were told that there would be no effect on Sara from this, other than an increased risk of a trisomy in any child she conceived, which would probably spontaneously abort at an early stage. I had had several miscarriages before two successful pregnancies, and these were retroactively attributed to the translocation.

My husband and I were tested, and he also carries the translocation. There is not much wrong with him except ADD. We found that his mother, also probably ADD but no other deficit, carried the translocation.

Sara was born at a university hospital in 1985 and the technology was not there to diagnose AS.

It is interesting to me that the translocation affects some of the same genetic material involved in AS.

Also of interest to me is the strong family history of female cancers in Jeff's mother's family. When I read that a breast cancer gene had been identified on chromosome 15, I got in touch with Fox Chase Cancer Center in Philadelphia, which does a lot of work on hereditary cancers. They were very interested in Sara and her progenitors, and they gave us the AS diagnosis a week after the geneticists at Childrens Hospital in Philadelphia did.

Does anyone else out there have a translocation at this site? How about cancers? In Jeff's mother's family, the three surviving daughters had two deaths from breast cancer, one survivor treated for ovarian cancer. Their mother died from what was called "liver cancer, " but which probably had metasticized from somewhere else. A brother died from "back" cancer. Another brother survives cancer-free.

Martha

Subject: Re: Genetics

Corinne,

So you've finally got the confirmation from your geneticist that Coralynn has a large deletion, and I guess recurrence risk has also been ruled out - I didn't see you write about this before. What your geneticist said is contradicted by Dr. Wendy Robinson's presentation at the Calgary Conference, as summarized in my message dated 21 August. She favored the hypothesis that deletions occur just after fertilization, i.e. during the early cell divisions of development of the affected child. Nevertheless, I haven't heard of any scientific evidence that deletions could be due to environmental causes, or to anything the parents had done.

Best Regards,

Heikki Taimio, dad to Liisa (6, del-) Finland

Subject: Re: Genetics

Corrinne

I was told the same thing----helps, doesn't it! I really believe God has a great plan for all of us and we just have to figure out what it is. We need to focus on the fact that our children have AS, what are we going to do about it and continue on from there. There's too much ahead to dwell on what happened and what if. Not to say that I'm not totally fascinated with genetic research and how it can help in the future. I just can't do it as I'm too busy seeing that Susan gets what she needs now.

Anne (mom to Susan 24 UPD).

Subject: Re: Genetics

Dear Martha,

Yes, Robertsonian 13/15 translocations are known to be an important cause of UPD, as reported e.g. in the OMIM entry, so Sara is not alone. It is remarkable, however, that both you and your husband carry the same translocation. I think you could have had children with Prader-Willi syndrome, too.

I did a little bit of research on ADD (= attention deficit disorder, right ?), and I found something very interesting: while the genetic and physiological causes of ADD are not fully known, it is believed that it may be due to imbalance of neurotransmitters in the brain and/or abnormal glucose metabolism. There you are ! Those are exactly the mechanisms that I (and I guess many others) have been suspecting for some time in the case of AS - and this also reinforces my belief that they are regulated by some gene(s) residing in chromosome #15.

About cancers, I really don't know, but what you write is very interesting - and worrying !

Take care,

Heikki Taimio, dad to Liisa (6, del-) Finland

Subject: Re: AS with normal genetic studies

Kelly Hampton wrote:

>The mystery of AS children with normal genetic studies continues... Continuing on this topic, didn't >Dr. Williams present a paper on the deletion negative, normal genetic studies AS child at the >conference (or is my brain in overload again!!)? I'd be really interested to hear what he said if >anyone has information.

Hi Kelly,

Yes, he did. In the records kept in a University of Florida repository, the proportion of AS cases with normal genetic studies was 23 % (1995). Some of these may show a genetic abnormality in more advanced tests, yet to be developed. According to Dr. Williams, del+, UPD and imprinting mutations are handled locally in the U.S., while normal genetic studies children are evaluated in Florida. I don't know if it is a common practice everywhere to send these cases to Florida. On the other hand, why shouldn't a local neurologist, pediatrician or some other specialist sufficiently familiar with AS be allowed to write a diagnosis ?

Dr. Williams' presentation drew heavily on the article, "Angelman Syndrome", jointly written by himself and by a few other experts. Assuming you've got it, let me be very brief. Given that a child has normal genetic studies, what other characteristics should be used to determine whether she/he has AS ? The four 100 % criteria won't do, as also other children could exhibit these features. Dr. Williams listed the following conditions that can mimic AS, particularly at an early age:

Methylene THFR deficiency ATR-X (alpha-that/MR) Rett syndrome Nonspecific conditions Autism spectrum Cerebral palsy Static encephalopathy Lennox-Gastaut syndrome

It is remarkable that the Smith-Magenis-Syndrome isn't on this list.

A wider approach needs to be taken to distinguish AS from these conditions. A points system for evaluation will probably be developed in the future as more will be known about AS. My impression was - much like Alice said - that not enough is known, that there are certain areas of confusion, and that the experts would rather refrain from saying anything than embark upon all sorts of speculations.

Meanwhile, Dr. Williams is using the following decisive features for discrimination between AS and other similar conditions:

Movement disorder Behavioral uniqueness Prognathia Protruding tongue Feeding problems

I hope this helps.

Heikki Taimio, dad to Liisa (6, del-) Finland

Subject: Re: AS with normal genetic studies

It's wierd that prognathia and feeding problems are on that universal list of clinical characterisitcs in AS. Emily had/has neither and her tongue doesn't protrude even 50% of the time, yet Dr. Williams diagnosed her clinically from a videotape when she was only 2 1/2 and deletion negative at that time. (A subsequent methylation test turned up deletion positive.) Interesting...

Marianne (Emily, 6, del+)

Subject: Re: AS with normal genetic studies

Marianne,

Dr. Williams surely didn't mean that all five of those characteristics need to be present in every case. To me, it seemed like he was somewhat unsure and was really using the movement disorder and behavioral uniqueness as decisive features. I guess diagnosing AS children with normal genetic studies is more art than science at this point.

Heikki Taimio, dad to Liisa (6, del-) Finland

Subject: Re: AS with normal genetic studies

Heikki, thanks for the information. Do you know of any test currently in development for deletion negative, normal genetic studies AS children? I've heard that Dr. Nicholls at CWRU is currently working on a test but will not consider testing a child unless they have a definite clinical diagnosis. Does anyone know anything more about this test? Also, could someone describe what feeding problems mean. Devin had reflux as an infant, but had no problems handling with her bottle, baby food, toddler food and started eating table food at about 18 months. In comparsion to my "normal" nieces she was delayed in acquiring feeding skills. Today she still has trouble with hard or very chewy textures (meat, hard cookies) but for the most part she eats just about everything (hates egg salad but will eat scrambled eggs). She drinks from a cup unassisted and can feed herself with a spoon (and a little bit of help). I guess I'm wondering if Devin fits the profile for feeding problems. Another also, Devin is 3, would prognathia be obvious at this age? Marianne, when Dr. Williams dx'd Emily did he cite specifics for his ulitmate conclusion? I'm sending the videotape of Devin next week so I'm just trying to prepare myself for what he may or may not say. Thanks everyone! Have a great weekend.

Kelly

Subject: Re: AS with normal genetic studies

Kelly,

I forgot to mention that I couldn't breastfeed Emily -- she had difficulty latching on...I tried to nurse and use supplement bottles, but I finally gave up. Emily needed a bottle with a larger hole, too, and took a long time to eat. She sucked very lightly.

Marianne (Emily, 6, del+)

Subject: Re: AS with normal genetic studies

Kelly,

After viewing the videotape, Dr. Williams sent me a checklist of AS characteristics and indicated whether or not Emily had them. He then used (I'm pretty sure) a 5-point scale, with 5 being certain clinical diagnosis. He rated Emily a 4, which was a highly probable rating but lacking some of the characteristics. I don't know if he still uses the same system. BTW, being able to hold a cup and drink independently and use a spoon at age 3 is way beyond where Emily is now at almost age 7. But, as I've written before, she seems to be more delayed in her skills than some of the other kids with AS.

Marianne (Emily, 6, del+)

Subject: Re: AS with normal genetic studies

Hi Kelly,

There are a number of research laboratories around the world which are developing more advanced tests. Dr. Nicholls is a prominent figure in the U.S., he should know what is going on, and if I were in your position, I would certainly get in touch with him.

In this context, feeding problems include, above all, difficulty in sucking and swallowing, plus uncoordinated tongue movements, spitting up and reflux, as explained in the article "Angelman Syndrome" by Charles A. Williams et al.. These occur during infancy, and I've not seen any study which would refer to the feeding problems of a toddler, altough there has been ample online discussion on them.

About prognathia - sorry, I really don't know.

Take care,

Heikki Taimio, dad to Liisa (6, del-) Finland