Stickler syndrome

In addition to their roles as health care providers and advocates for patients with genetic disorders, Prs have a vital role to play in the genetics research arena. Studies in genetics seek both a further understanding of the genetic component of disease and disability and to identify effective interventions for those disorders. Below, two PTs who are involved in researching genetic disorders provide a look at some past and current studies.

Intramural Research at NIH

Genetic errors are responsible for an estimated 4,000 hereditary diseases.1 Often classified as "orphan diseases," these diseases typically receive little attention from privately funded investigators in the biomedical field. As a result, little is known about these diseases or how best to treat them.

To address this problem, the National Center for Human Genome Research was established by the National Institutes of Health (NIH) and the Department of Energy with the primary goal of identifying genes responsible for rare and common hereditary disorders. The Human Genome Project, which began with a plan to decode and map human genes, has been revised and expanded to explain the role of genes in health and disease.

The Division of Intramural Research of the National Center for Human Genome Research was established in February 1993 to apply genome research to the study of inherited disorders through clinical trials carried out at the NIH Warren Grant Magnuson Clinical Center. In 1995, the National Center for Human Genome Research became the National Human Genome Research Institute. The Physical Therapy Section of the Rehabilitation Medicine Department at the Clinical Center provides therapeutic services to patients in clinical trials, including patient populations with rare disorders. PTs see patients both to address clinical needs and to collect data for research protocols. Physical therapy research is carried out either independently, collaboratively or through agreements with the private sector. (For more on the PTs in the intramural research program at NIH, see "A Foot in Both Worlds," in the September 1998 7.)

In 1997, the National Human Genome Research Institute initiated two research studies that involve PTs as integral members of the clinical research team. One study is to investigate skeletal dysplasias, which are heritable disorders of the skeleton that result from defects in bone and cartilage formation. The purpose of the study is to determine the natural history of the diseases and the relationship between genotypes and phenotypes. Investigators hope to generate a comprehensive description of skeletal dysplasia in regard to the pathophysiology, course of disease, impairments, disabilities, and other issues. Such an understanding might provide the basis for additional research funding to study other rare disorders.

As part of that study, researchers also are investigating type II collagen disorders such as Stickler syndrome (hereditary ophthalmopathy). Onset of the disease typically is within 10 days of birth; however, some patients seen in conjunction with this study were diagnosed through genetic testing in adulthood after the birth of their own children with the disorder. Other onsets have been documented after orthopedic injuries or during competitive sports or were initially misdiagnosed as simple arthralgia. The variability in the onset of diagnosis is largely dependent on the phenotype of the individual.2,3

The other study, the Heritable Connective Tissue Disorders protocol, was initiated to study clinical and molecular genetic defects of heritable connective tissue disorders. Currently, PTs provide therapeutic intervention for these subjects. In addition, a pilot study investigating specific musculoskeletal deficits may develop as an outcome of physical therapy questions generated from the research project. The current protocol includes individuals with contractural arachnodactyly, Marfan, and Stickler syndromes, and Ehlers-Danlos syndrome, the primary diagnosis of this protocol's subject group. Ehlers-Danlos syndrome is an inherited connective tissue disorder for which the specific gene defect has not been found.1,3,4

Studies currently underway at NIH provide PTs with challenging clinical populations and are generating a series of research questions. Eventually, such information may benefit rehabilitation professions on a national and international scale. Currently, these patients require careful differential diagnosis and innovative treatment planning, as there are few evidence-based practice guidelines for therapists to use as references. Through careful observation and documentation, NIH therapists are obtaining critical preliminary findings to support future therapeutic treatment of these patients.

References

1 The Human Genome Project: From Maps to Medicine. Washington, DC: US Department of Health and Human Senices; 1996. DHHS/PHS Publication No. 96-3897.

2 Jones K Smith's Recognizable Patterns of Human Malformation. Philadelphia, Pa: WB Saunders; 1997.

3 Schumacher H, Kuppel JH, Koopman WJ, et al. Primer in Rheumatic Diseases, Tenth Edition. Atlanta, Ga: Arthritis Foundation; 1993: 249-251.

4 Kelley WN. Textbook of Internal Medicine. Philadelphia, Pa: JB Lippincott; 1989.

For further information about the National Center for Human Genome Research or the Physical Therapy Section of the Rehabilitation Medicine Department at NIH's Warren Grant Magnuson Clinical Center visit the Web sites at www.nhgri.nih.gov/ and www.cc.nih.gov/rm/pt/pt/section.

LCDR Michaele R Smith, PT; is a commissioned officer in the Office of Public Health and Science (formerly known as the US Public Health Service) and currently is the education coordinator of undergraduate, graduate, and volunteer students in the Physical Therapy Section of the Rehabilitation Medicine Department at the Warren Grant Magnuson Clinical Center, NIH.

Copyright American Physical Therapy Association Mar 1999
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