Stickler Involved People Newsletter September 2002

September 2002

Coordinator Comment

My family was at a “sit-down” restaurant last week and I noticed a family at another table. Both parents were deaf and mute. The children were preschool age, and I thought “how lucky to have two languages at such a young age.” Later, one child was told something that made him mad. He responded with a two-year-old’s-fit. Then, I thought “well, there are advantages to not hearing”.

I have these mixed-blessing feelings about our involvement with Stickler syndrome. There are so many blessings that we have received through the years of being involved with you. We have our share of struggles, but “there are advantages.” I hope that you had a great summer, along with your challenges.

ANNOUNCEMENT

Stickler Involved People is very proud to announce the creation of the Gunnar B Stickler Scholarship Fund. Dr and Mrs Stickler have generously donated the start-up money for a fund to provide high school seniors, who have a diagnosis of Stickler syndrome, with a four year scholarship. The committee has completed the hurtles for the IRS and has a set of criteria established. Applications will be available after January 1, 2003.

This scholarship fund is now available for your tax deductible contributions!! Please consider helping by making a donation in honor of your parents, or your child or your spouse. This makes a good Christmas gift suggestion!

CONFERENCE 2002

Notes thanks to Kevin Cunningham

Drs. Gunnar Stickler, Clair Francomano (Genetics), Ruth Liberfarb (NIH Stickler Syndrome [SS] researcher), Paul Sponseller (Orthopedist), Irene Maumenee (Ophthalmologist) and Jay Shah (Physiatrist) spoke at the conference.
Affects / Features-Dr Francomano

Craniofacial

Mid-face underdevelopment around eyes … sometimes a scooped out appearance
Underdeveloped cheek bones
Flat facial profile
Cleft palate [25%] (ranges from bifid uvula or high palate to full cleft palate)

Ocular

Frequent eye exams required, particularly for children!
Vitreous degeneration (can manifest as floaters)
Retinal holes, tears and detachments
Myopia (seen in almost 100% SS patients)
Cataracts/Glaucoma (later in life)

Auditory

Progressive sensory-neural hearing loss (typically follows a progression of high frequency to low frequency loss)

Musculoskeletal

Growing ends of long bones
Early onset of degenerative arthritis
Scoliosis (lateral), kyphosis (fore-aft) [less common]
Pectus excavatum or carinatum (The breastbone’s development is very sensitive to any deviations in the development of the ribs / spine)
Chronic musculoskeletal pain
Osteoporosis (low bone density)
Reduced upper to lower body height ratio (height reduced due to spinal involvement, not the long bone overgrowth seen in Marfan syndrome)
Increased arm span to height ratio
Hands / Fingers are relatively long and thin
Double jointed
Knees – can sometimes bend backwards or “knock-kneed”

Cardiac

Mitral Valve Prolapse only 4% in known SS patients, general population is 2% occurrence

Genetics

Autosomal dominant: 50% chance child unaffected if one parent has SS, 25% if both parents have SS; doesn’t skip generations (unaffected children don’t “pass it on”)
Likely a result of “natural” genetic mutation, not environmental factors. (Premature stop codes on the collagen protein.)
Lifespan is not affected because one has Stickler syndrome
Stickler mutations will affect only one of those two, thus only half the number of collagen protein chains will be made, therefore the body makes half the amount of collagen it would make otherwise
In the future, gene therapy may make it possible to alter the expression of the unaffected gene. (Chemicals that bind to promoter to turn “on” the unaffected gene, thus getting an increase in the body’s collagen production) This may be possible in 12 yrs.
18 types of collagen have been identified
Type I primarily in bones and skin
Type II primarily in cartilage and vitreous
Type III primarily in blood vessels
There is a popular belief that glucosamine and chondroitin sulfate decrease osteoarthritis symptoms. National Institute of Complimentary and Alternative Medicine to do a large sample study to quantify this. If that is positive, then a study of affects in SS population will be worthwhile.

Major research areas

Identify unknown genes
Relationship of genotype to phenotype
Identity of modifying genes
Determine frequency of specific complications
Cleft
MVP
Osteopenia/Osteoporosis
Treatment of chronic musculoskeletal pain

Musculoskeletal-Dr Sponseller

Manifestations
Scoliosis
Premature osteoarthritis
Pectus deformities (sternum development has a high dependency on development of ribs and spine)
Osteoporosis
Marfanoid habitus (tall, thin, height ratios)
Various hip and femur woes

Spinal involvement

Adults w/ back pain: 86% [15% in general population], pediatric: 25%
Spinal abnormalities: almost always
Chronic back pain common and often disabling
Abnormalities progress w/ age and associated w/ back pain
Although common, scoliosis is generally self-limited (40 deg curve is considered serious, 20 degrees is mild to moderate)
74% have endplate abnormality (narrowing & wedging of disks)
64% have Schmorl nodes (notches in vertebra, due to weak endplate resulting from collagen degradation)

Treatment

Physical therapy / exercise
Bracing
Analgesic medications
Surgery as a last resort only (…particularly w/ disks, removing one disk will only load up the other already weak disks. If a disk is herniated or severe scoliosis then surgery is warranted.)

Hips

79 % adults reported hip pain

Slipped Epiphysis

Sudden onset of limp in older children (teens)
Simple surgical fix (screw femoral head into a ball joint). Failure to do the surgery will result in permanent hip disability.
Seen in teens because collagen is being stressed to the max during this time of rapid growth. Patient reports of hip pain spike during teens then decrease ~50%. Linear increase with age of number of patients reporting hip pain.

Hip Replacement

Good pain relief
Duration of the replacement is a problem in young adults
Not studied in Stickler syndrome

Stickler Syndrome Diagnostic Criteria-Dr Liberfarb

(Based on unpublished, as of 6/15/2002, results of NIH Stickler study) {PLEASE note that this criteria is being revised, due to input from attendees at the conference)
COL2A1 mutations is 18 patients from 4 families
Used clinical characteristics to formulate the criteria
Applied this criteria to 36 patients clinically diagnosed (but lacking molecular data & 18 clinically &/or molecularly excluded.

Stickler Syndrome Diagnostic Criteria

Oral-Facial Abnormalities – 2points
Ocular Abnormalities (vitreous degeneration or retinal detachment) – 2 points
Auditory Abnormalities (2 point max)
o2-points

Age < 20: >= 20 dB at 4-8 kHz
Age 20-40: >= 30 dB at 4-8 kHz
Age > 40: >= 40 dB at 4-8 kHz

o1-point

Hypermobile tympanic membranes
Skeletal Abnormalities (2 point max)

1- point

Femoral head failure (slipped epiphysis or Legg-Perthes like disease)
Osteoarthritis before age 40
Scoliosis, spondylolisthesis, or Scheuermann-like kyphosis

Family History / Molecular Data

o1 point for independently affected 1st degree relative

Diagnosis requires 5 points total and presence of cleft palate, ocular abnormalities or high frequency sensorineural hearing loss

Ocular-Dr Maumanee
Complications
Early glaucoma
Cataracts
Retinal detachments

Vitreous

Is nominally a gel consistency
Is a very fine mesh of connective tissue
Sticker patients have vitreous degeneration
Develop strands within the vitreous (metabolites accumulate)

Strands can attach to retinas and cause pulling

Localized pockets of liquid (as opposed to gel)

Excess liquid causes increased pressure within the eye. Lens metabolism doesn’t work exactly right and thus can lead to the lens problems.

Wagner Syndrome

Similar to Stickler syndrome with respect to the eyes
Ophthalmologists are more familiar w/ Wagner syndrome than Stickler syndrome (will see a Stickler patient and call it Wagner syndrome). Few will know of Stickler syndrome. Treatment for Wagner syndrome would be appropriate for a Stickler syndrome patient.
In Wagner syndrome the maculars stretch, so the eyes rotate outboard, independently, for image overlay.

Eye Exams

Frequent!
Children often won’t complain until the second eye is involved. (If retina detaches in one eye, they’ll just compensate and go merrily along, until problems arise with second eye. Usually, it is way to late to do anything to save vision in the first afflicted eye when this is the case.)
3 month intervals, 6 month intervals, 1yr interval when a teenager.
Lens Implants
More complications with membrane overgrowth in younger patients. Becomes less of a problem with teenagers.

Laser (Lasik) surgery

No known (at this time) reason why stickler’s patients would be at particular risk. (Avoid if large pupil or very high myopia [8 to 10 diopters]
Still, worth tracking the results when Stickler patients have Lasik, to determine if there is an inherent risk.

Myofascial Pain Syndrome

– Dr Shah

Pain that is muscular in origin, but can manifest in other, seemingly unrelated parts of the body.
If you can make a muscle relax then pain stops, implies that the pain was muscular in origin.
Dr. Janet Travell pioneered myofascial genesis of pain
Travell identified “trigger points” in muscles, later found that there was a 75% correlation with acupuncture points.
Pain that is myofascial in origin can be misdiagnosed as being from a “typical” cause.
If treatment of “commonly diagnosed” aliments doesn’t work, it may be worth seeing a physiatrist (Dr. of physical medicine and rehabilitation) to determine if it may be myofascial in nature.
Physiatrists may use massage, TENS, and/or acupuncture to relax muscles.
These techniques have been used in conjunction with collagen disorder clinics / trials at NIH.

Mindfulness Based Stress Reduction for Treatment of Chronic Pain-Dr Francomano

Uses meditation and guided imagery to relax and focus on areas of the body that need healing
Chronic pain causes increased anxiety, depression, anger and interpersonal concern. This is a downward spiral as anxiety, etc make one more sensitive to pain.
Use of MBSR & treatment of muscle trigger points have been shown good results at NIH

Pre-Implantation Diagnosis (in family planning)-Dr Francomano

Now only possible if gene & the mutation of that gene is known
Do in vitro fertilization then conduct studies on one of the cells (can take one cell once you have 8 … the remaining 7 will continue division to produce normal baby) to see if mutation is present. If not present, then implant into uterus.
This isn’t done often. Probably has been done a couple of dozen times for Marfan syndrome.
Patients / Parents will be presented with conflicting information. One must be one’s own advocate, seek knowledge and make own decisions.

URLs

SAVE SIP

WE promised to not “bug” you about sending your email address, for the newsletter. Just please remember that if you CHANGE email addresses, send a notice to sip@sticklers.org

Stickler – The Elusive Syndrome

This book, written by Wendy Hughes, explains, in layman terms, the condition, possible medical problems, and how it can affect individuals. The approach is positive and leaves the reader with hope and skills to manage Stickler syndrome.

Wendy’s book is available for $28.50 payable to Stickler Involved People. The cost includes exchange to British pounds, shipping and handling. Send requests to: Stickler Involved People, 15 Angelina, Augusta, KS 67010

SIP will also forward membership fees to SSSG, to save you monetary exchange fees.

Drug Help

A “Medicine Program” that offers assistance to individuals who are regularly required to take prescriptions, but lack adequate income, may help you. There is a one time $5 filing fee per prescription. The Medicine Program staff will fill out the paperwork to get a person into one of the drug manufacturer sponsored patient assistance programs. This is available to anyone and any age. For more information call 1-573-996-7300 or go to www.themedicineprogram.com