.) Progress in identifying the causes of hereditary deafness and communicative disorders has been accelerated by recent advances in molecular genetics. Identification of the genes responsible for syndromic causes of hearing loss is a crucial step toward the ultimate understanding of the development of the ear and hearing impairment. Crouzone syndrome (CS) is an autosomal dominant condition characterized by premature craniosynostosis, hypoplastic maxilla, shallow orbits with proptosis, and external auditory canal atresia.Up to 50% of CS patients have hearing loss, both conductive and sensorineural. In addition, these patients have difficulty with speech and communication development secondary to their craniofacial malformations. The polymerase chain reaction (PCR) is a powerful molecular genetic technique which permits amplification of small amounts of DNA. This technique can be used to search for genomic markers termed microsatellites (CA repeats). Linkage between these markers and CS will then be tested for using computer programs such as LINKAGE. Successful use of these molecular techniques requires the identification of a large, cooperative family with many affected members. A family with 10 affected members and a six-generation pedigree is cooperating with this investigation and 11 other families have been identified. Gene mapping by linkage analyses would be facilitated if the search could focus on one chromosome; however, no chromosomal abnormalities have been reported to be associated with CS. Chromosome 7p and genes controlling morphogenesis and development, such as HOX, PAX, POU and zinc finger, are candidate regions that will be evaluated for linkage to CS. If no linkage is demonstrated to these candidate genes, a systematic, genome-wide search will then be performed. DNA from other CS families will be used to confirm linkage or evaluate genetic heterogeneity.
