By Keith S. Wexler, MBA,CFO, CIO – Maternal Fetal Medicine, Prenatal Diagnosis and Biotech/Life Sciences Consultant, 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
Beckwith Wiedemann Syndrome is characterized by:
- Abdominal wall defects
- Large tongue
- Fetal & post-natal overgrowth (e.g. liver, spleen, adrenals, kidneys, pancreas)
- Increased risk for malformation and some cancer (e.g. kidney, liver)
- Variable developmental delay
- Autism Spectrum Disorder
Mutations in the NSD1 gene on chromosome 5q35.2-35.3 and mutations and deletions of imprinted genes on chromosome 11p15.5 region have been described and in some cases of Russell-Silver Syndrome and Sotos Syndrome.
Beckwith Wiedemann Syndrome is believed to be inherited in an autosomal dominant manner (50%).
Paternal uniparental isodisomy (both copies of the same chromosome come from the same parent) has also been described on chromosome 11p.
Background: 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.
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. Beckwith Wiedemann 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.