Down Syndrome/Rare Disorders  
Linda Blevins, Division Director
The MAGIC Touch • Fall 1997
Vol. 8 Issue 3, pp. 10-1
  Reprinted with the permission of The MAGIC Foundation
1327 N. Harlem Avenue, Oak Park, IL 60302-1376
1 (800) 3 MAGIC 3
(708) 383-0808 Fax: (708) 383-0899

The 1997 MAGIC conference was a huge success. Families traveled from Alaska and Hawaii and there was international representation from India, England just to name a few countries. All of these families came together for one reason, overriding concern for their child's growth disorder.

Friday's educational seminars allowed families to gain a greater insist into their child's growth or endocrine disorders. Networking session allowed families the opportunity to share valuable personal information and to question the physicians on a one to one basis. Opportunities of this nature are seldom allowed in time managed doctors offices. Thank you to the medical professionals for their generous gift of time and talent.

Other major contributors to the MAGIC conference were the pharmaceutical companies and the home heath providers. The sponsorship and information support that MAGIC receives is invaluable. One of the pharmaceutical representatives related that the MAGIC conference is the highlight of his year. He finds it an overwhelming and humbling experience as parents relate their child's positive responses to growth hormone and to see children whose lives are being dramatically changed by this drug. As so many of us said at the conference "Thank God for growth hormone".

MAGIC attendees had a lot of fun, a cruise down the river, bingo bash, karaoke and line dancing and the silent auction. We are now the proud owners of a 5 foot Wiley. E. Coyote. We buckled him in a car seat and drove him back to Georgia. I also have an autographed picture of Clint Eastwood, "Make my day"!

Often times in children with Down Syndrome there are concerns about the dental structure. I have placed an article, Orofacial regulation therapy in children with Down syndrome, using the methods and appliances of Castillo-Morales from the Journal of Dentistry for Children (57, #6) p. 442-444. The article discusses using palatal expanders to widen and lower the high palate that is commonly found in DS.

Recently I attended a lecture in Shreveport, LA and had the opportunity to listen to Dr. Stephen Evans. He studied under Dr. Castillo-Morales and is using his methods in his dental practice. According to Dr. Evans, most Down syndrome individuals have what is called a midface deficiency which includes underdeveloped maxilla, premaxilla, bridge of the nose and sinuses, which results in that very flat face appearance of individuals with DS. Dr. Evans feels that orthodontic intervention with tailored palate expanders (with dental toys and tongue stimulators) to widen the palatal arch will affect facial appearance and tongue positioning. The conference materials are on file at MAGIC.

In addition, I spoke with Dr. Kirt Simmons D.D.S., Ph.D. He is an Assistant Professor of Orthodontics and is on the Cranial Facial Anomalies Team at the University of North Carolina School of Dentistry and he is a medical advisor for MAGIC. Dr. Simmons has sent some additional materials on palate expanders, which are on file. Thank you Dr. Simmons for your invaluable assistance.

This is a very interesting article sent to me by BG of Cleveland. It is written by Dr. Patricia Kane. Dr. Kane utilizes metabolic testing and nutritional supplementation to recover children from autism. The article Reversing Autism with Nutrition, Alternative Medicine Digest, Issue 19, profile a child Alex who slid into autism after an MMR vaccination.

Blood chemistry profiling with Carbon Base Corporation of Incline Village, NA revealed Alex's system was unbalanced in three major categories. First his electrolytes, which control membrane traffic, ammonia removal and digestion were out of balance. Second, he had an imbalance in nitrogen levels. Nitrogen levels are a key component is utilizing amino acids to form protein. Abnormal nitrogen and electrolyte levels impact kidney and liver function adversely. Thirdly, this test showed the child's production of red and white blood cells were altered impacting his immune system. Slowly, dietary changes and nutritional supplements were introduced to Alex. Alex responded positively with increased eye contact and socialization. "The future remains bright for Alex as the autistic features have slipped away with the help of individually tailored and the continuing metabolic support of his immune, endocrine and nervous systems".

Individuals with Down syndrome experience metabolic disturbances due to the overexpression of genes located on the 21st chromosomes. It is not uncommon to have a child with DS to have a secondary label of ADD, PDD or Autistic. I thought this article would be helpful to some of our parents.

The MAGIC conference, as with every conference I attend, allows me to gather more information. I get one more piece of the Down syndrome puzzle. I can connect a few more dots.

Dr. Bernard Silverman, Professor of Pediatrics at Children's Memorial Hospital in Chicago discussed the possible causes of growth hormone (GH) deficiency. Dr. Silverman spoke about the timing and feed back system between the hypothalamus and the pituitary gland. Three major hormones involved are:

Growth hormone releasing hormone is released from the hypothalamus and tells the pituitary to release GH.
Is released from the pituitary gland by GHRH. GH travels to the liver and stimulates the release of insulin growth factor-1 (IGF-1).
The liver releases IGF-1 and it travels to receptors located through out the body. IGF-I controls the growth of many organs (skeletal, muscular, skin and central nervous system).
Factors disrupting the regulation of GH can be caused by organic factors such as tumors, radiation and surgical treatment of the tumors, dwarfed or missing glands. Some GH failure can be traced to infections from tuberculosis, meningitis or even trauma. In addition perinatal insults such as a breech birth, hypoxia (no oxygen) or birth trauma can affect the functioning of the delicate endocrine system. By far the chief classification of GH deficiency is hypothalamic dysfunction.

What do studies on children with Down syndrome have to say on this topic? It is generally believed that in people with Down syndrome the pituitary gland is intact and functional. In 1993 Dr. Pueschel studied the response of growth hormone secretion in eight growth retarded children with DS. When he utilized GHRH to directly stimulated the pituitary to release growth hormone, seven of the eight responded in a normal range (3). Yet, when L-dopa was used to stimulate die hypothalamus, five children (63%) had low response levels When another provocative, clonidine, was used to stimulate the hypothalamus, six children (75%) were classified as low responders. A low growth hormone response is < 10 ng/ml. Pueschel states "It is postulated the children with Down syndrome have both anatomical and biochemical hypothalamic derangements that may result in decreased growth hormone secretion and reduced linear growth" (1).

Castells finds a similar pattern of normal peak scrum GH concentrations when the pituitary is directly stimulated with GHRH (2) and subnormal GH response levels with hypothalamic stimulatory tests (3,7). When Dr. Castells conducted levadopa and clonidine stimulatory test on twenty children with DS. Seven of the twenty children (35%) experienced a diminished GH response (<10 ng/ml) to the provocative stimulation (3).

Anatomical studies by Dr. Wisniewski indicate "morphogenic abnormalities in the hypothalamus of DS patients with diminished number of neurons in the arcuate and ventromedial nucleis. The decreased in neurons per square millimeter suggest a deficiency in GHRH neurosecretory function of arcuate ventromedial nuclei" (4).

Annerén of Sweden looked at IGF-1 levels in 5 growth retarded children with DS and discovered they maintained low levels of insulin growth factor 1. Annerén treated these children with GH for six months, "during this period the growth velocity doubled and the serum IGF-1 levels were restored to normal. Thus DS children respond to GH treatment" (5,6). Castells and Wisniewski found in their growth hormone study with children -with DS, that plasma concentrations of IGF-I normalize with GH treatment (8).

How important is IGF-1? Insulin growth factor 1 is the active component of the growth hormone system. IGF-1 is the work horse. It goes out and binds to receptors (IGF-1R) located in muscle, bone, tissue and nerves. IGF-1R "are expressed extensively throughout the brain" (9). Dr. Sara who worked with Dr. Annerén on the GH studies says "there is absolutely no doubt in my mind that IGF-1 has a role in brain development" (10).

Yes, there are many questions to be asked and many questions to be answered. For my son Jordan, the only means to resolve some of these issues was through testing. Testing revealed unmeasurable levels of the important growth factor IGF-1. Provocative testing -with hypothalamus stimulators resulted in a response less than 10 ng/ml. Jordan was classified as growth hormone deficient and started on treatment on July 1994. Jordan's response to growth hormone has been tremendous.

  1. Pueschel, SM: Growth hormone response after administration of L-dopa, clonidine, and growth hormone releasing hormone in children with Down syndrome. Res Dev Disabil 1993;12(4):291-298.
  2. Castells S. Torrado C. Geiato MC: Growth hormone responses to GH releasing hormone suggest hypothalamic dysfunction as a cause for growth retardation in Down syndrome. Pediatr Res 1991:29-35.
  3. Castells S, Torrado C, Bastian W, Wisniewski KE: Growth hormone deficiency in Down's syndrome children. J Intellect Disabil Res 1992 Feb:36(Pt l):29-43.
  4. Wisniewski KE, Bobinski M: Hypothalamic abnormalities in Down syndrome. Prog Clin Biol Res 1991;373:153-167.
  5. Annerén G, Sara VR, Hall K, Tuvemo T: Growth and somatomedin responses to growth hormone in Down's syndrome. Arch Dis Child 1986 Jan;61(l):48-52.
  6. Annerén G, Gustavson KH, Sara VR, Tuvemo T: Growth retardation in Down syndrome in relation to insulin-like growth factors and growth hormone. Am J Mod Genet Suppl 1990;7:59-62.
  7. Castells S, Beaulieu I, Torrado C, Wisniewski KE, Zamy, Geiato MC: Hypothalamic versus pituitary dysfunction in Down's syndrome as cause of growth retardation. J Intellect Disabil Res 1996 Dec;40 (Pt6):509-517.
  8. Torrado C, Bastian W, Wisniewski KE, Castells S: Treatment of children with Down syndrome and growth retardation with recombinant human growth hormone. J Pediatr 1991 Sep;119(3):478-483.
  9. Castells S: Hypothalamic dysfunction as a cause of growth retardation in Down's syndrome: effects of recombinant human growth hormone. Intl Conference on Growth in DS, Sept, 1994.
  10. Castells S, Wisniewski KE, Growth Hormone Treatment in Down Syndrome. John Wiley & Sons, 1993 (213).
Over the Fourth of July, our family had the pleasure of basking at a local Atlanta water park. It was tons of fun! We happened to run into a French family (now living in Cleveland, Ohio) whose seven year old daughter, Victoria, has Down syndrome.

Victoria was quite remarkable with her bilingual speech skills in English and French. As we sat under the hot Georgia sun, Victoria's parents and I began to share our stories. This family related to me how at one month old they were sent to the Lejuene Institute in Paris. Doctors at the Lejuene Institute prescribed a vitamin supplement regime diet constituted of B6, B12, folic acid, methionine and other supplements. When they came to the US, it was far too difficult to obtain the mixture, so they had stopped.

How wonderful that some where in the world, physicians treat the metabolic disturbances in children with Down syndrome. It was quite obvious from Victoria's speech skills and her physical abilities that she had benefited from the "early intervention".

  Revised: July 17, 1999.