Autosomal dominant primary empty sella syndrome, congenital glaucoma, sensorineural hearing loss, and tooth dysgenesis. S. Finzi¹, J. Auguste¹, E.A. DelBono¹, J.L. Haines², J.L. Wiggs^1,3. 1) Ophthalmology, New England Medical Center, Boston, MA; 2) Program in Human Genetics, Vanderbilt School of Medicine, Nashville, TN; 3) Division of Clinical Genetics, New England Medical Center, Boston, MA.
   Primary empty sella syndrome results from a defect in the diaphragm of the pituitary sella that causes the subarachnoid space to extend into the sella turcica. Inherited forms of this condition have been previously associated with osteosclerotic dysplasia and cranio-facial deformities. A gene responsible for this condition has not been identified, although two patients with primary empty sella syndrome, mental retardation and skeletal abnormalities have been found to have a tandem duplication of Xq13-q21. We have identified a three generation pedigree with 11 affected individuals demonstrating the novel association of primary empty sella syndrome with ocular defects, sensorineural hearing loss and tooth abnormalities. Several affected individuals also have a flat mid-face and a high-arched palate. The ocular defects include: congenital glaucoma, posterior embryotoxon, and lens coloboma. The hearing loss develops in the second to third decades and is associated with periodic vertigo characteristic of Menieres disease. Tooth abnormalities include: delayed secondary dentition, malformed incisors, and extra teeth. Enlargement of the sella turcica was determined by MRI. There was no indication of hydrocephalus or pituitary dysfunction in any of the family members with sella turcica enlargement. Affected individuals are present in three consecutive generations, and equal numbers of males and females are affected. Male to male transmission supports autosomal dominant inheritance. Cytogenetic analysis did not reveal any deletions, insertions, inversions or translocations. Genetic linkage studies using markers flanking existing loci for congenital glaucoma or Axenfeld-Rieger syndrome indicate that this pedigree is not linked to any of these previously identified regions. A genome screen designed to determine the location of a gene responsible for this interesting syndrome is currently underway.