By Keith S. Wexler, MBA, CFO, Business Development Director GENASSIST, Inc.
Paul Wexler, M.D., F.A.C.O.G., Medical Director, GENASSIST, Inc.
Clinical Professor, Department of OB/GYN, University of Colorado Health Sciences Center
Clinical Professor, Division of Genetics/Dept. of Pediatrics, Univ. of Colorado/The Children’s Hospital
Zellwegers Syndrome – is inherited in autosomal recessive manner. Carrier frequency nay be has high as 1 in 18.
If both parents are gene carriers, there is a risk of 25% (1:4) for each child to manifest the disease.
At least three different genes have been described for peroxisome deficiency.
Children with the disease symptoms may be variable but may include:
- Hearing loss
- Liver & kidney abnormalities
- Vision problems
- Some children may manifest life threatening problems
It is estimated that there are between 4,000 and 20,000 diseases (with over 7000 rare genetic diseases) and several companies are offering screening panels for the carrier state of several hundred conditions and the possible predisposition for various cancers including some hematologic and neurologic malignancies.
Rare Disease affects 1 in 2000 people. 7% of the population will be affected with a rare disease in the lifetime.
Rare Genetic Disease affects 1 in 200,000 people. The registry established that there are an average of 4200 cases per Rare Disease.
National Organization of Rare Diseases established 1983 by Abbey Meyers and others got Orphan Drug Act passed 1983.
Analysis: One of the greatest dilemmas facing the healthcare provider is when a family presents with a positive family history of a very rare genetic disease and/or syndrome (e.g. Zellwegers Syndrome) and the family wants to know from the healthcare provider:
- Whether the disease and/or syndrome is inherited (autosomal dominant manner (50%), autosomal recessive (25% if both parents are gene carriers) or sex (X) linked (50% of males will be affected, 50% of females will be carriers), multifactorial (interaction of multiple genes with the environment, both genetic and non-genetic factors)?
- Whether the disease and/or syndrome is sporadic (due to a new mutation) and might or might not reoccur in a family?
- Whether the disease is caused by a Microdeletion?
- Whether there is testing for the disease and/or syndrome?
- If there is testing, is prenatal diagnosis and/or Preimplantation Genetic Diagnosis (PGD) available?
Furthermore, if screening and/or testing is available, the healthcare provider has the responsibility of deciding whether to recommend testing which may or may not detect patients who are carriers or affected with one or more disorders.
If a test returns as “carrier” most conditions identified will require testing the partner since the majority of the conditions tested for are inherited in an autosomal recessive manner [inheritance of one disease causing (deleterious) gene from each parent].
Since not all screening laboratories are contracted with insurance companies and panels currently offered may screen from 3 to 250 diseases, the healthcare provider will need to decide which tests to order and which laboratory to use.
However, the ACOG guideline does not set up a specific pre pregnancy panel nor recommend how many diseases or which diseases should be tested for except for those already recommended [e.g. Cystic Fibrosis, Fragile X, Spinal Muscular Atrophy (SMA), some “ethnic” panels, etc.].
Some laboratories are now offering “customized” panels developed by the healthcare provider in consultation with the laboratory based on the individual’s personal and family history and background.
With the increasing availability of such panels and the reduction in the cost, the demand for larger panels and the need for interpretation of laboratory results for the healthcare provider and the patient will continue to increase.
Likewise, it can also be expected as the number of diseases tested for increases, a greater percentage of “variants of uncertain clinical significance” will also increase. Interpretation, explanation and additional recommendations for monitoring and follow-up of the individual screened and other family members will also be required.