Genetic Analysis of Fraser Syndrome and Fryns Syndrome

Overview

This study will examine blood or other tissue samples from patients with Fraser syndrome and patients with Fryns syndrome to try to identify the gene responsible for these diseases. Fraser syndrome is characterized by congenital abnormalities including cryptophthalmos (lack of eyelid formation), syndactyly (webbed fingers or toes) and abnormal genitalia. Patients may also have abnormalities of the nose, ears and larynx (voice box), cleft lip or palate, and kidney agenesis. Fryns syndrome is characterized by hernia through the diaphragm, cloudy cornea, coarse facial features, cleft lip or palate, abnormal fingers and toes, heart, kidney and brain malformations and hydrocephalus (accumulation of fluid around the brain). This protocol consists of laboratory study only; it does not involve patient care or patient counseling. Patients with Fraser syndrome or Fryns syndrome are eligible for this study. Parents and healthy siblings of patients will also be included for genetic study, and parents of children with undiagnosed multiple congenital anomalies syndromes will be included for comparison study. Participants will provide a blood sample (about 8 to 10 teaspoons from adults; 1 to 3 teaspoons from children) or sample of skin cells collected by swabbing the inner surface of the cheek. Some patients may undergo a skin biopsy, in which a small skin sample (about 1/8-inch in diameter) is surgically removed. The tissue samples will be used to obtain DNA (genetic material) for laboratory testing. A permanent cell line-a collection of cells grown in the laboratory from the original tissue specimen-will also be established to enable additional testing in the future.

We would like to determine the molecular genetic etiology of two rare human malformation syndromes, Fraser syndrome (OMIM 219000) and Fryns syndrome (OMIM 229850). To date, we are unaware of molecular genetic studies that have been performed in either syndrome. We are planning to perform molecular genetic studies on DNA specimens from affected individuals ascertained outside NIH by other clinicians and/or reported in the medical literature. Should these studies prove fruitful, we would plan to expand this work to a combined clinical and molecular study to fully delineate the phenotypes associated with these disorders. We plan to collect DNA specimens from affected patients and from unaffected siblings and parents and to evaluate the specimens in the laboratory by linkage analysis, physical mapping, candidate gene characterization and mutation screening. If the causative genes(s) for either syndrome are identified, then mouse models of the diseases may be developed and cell biologic studies of normal and mutant proteins may be undertaken. The cloning of these genes would enable better characterization of human developmental processes and improve patient counseling for individuals and families affected by these diseases.