Autosomal Dominant Gillespie syndrome in 4 generations with highly variable expressivity and incomplete penetrance. J. Gaudelus, B. Heron, P. Bitoun. Dept Pediatrie, NeuroPediatrie & Genet Med,CHU Paris-Nord, BONDY,93143cedex France.

   Gillespie (1965) described 2 sibs with aniridia, cerebellar ataxia and mental retardation. A total of 21 patients have been described including 9 sporadic and 12 in 5 families; 3 including the princeps case have described affected sibs and 2 have described vertical maternal transmission. Etiology and transmission remains unclear and has generally been reported as autosomal recessive although no consanguinity has ever been reported. Most case reports mention aniridia but indeed description is that of iris hypoplasia since most patients have a minimal iris collarette. All patients have been reported with cerebellar ataxia and some with cerebellar hypoplasia , mental retardation and one with pulmonic stenosis. We report a case of iris hypoplasia in a 3 year old girl with hypotonia, psychomotor and speech delay and cerebellar ataxia with a normal M.R.I. and normal high resolution chromosomes all compatible with the diagnosis of Gillespie syndrome(GS). Family history is significant for a 30 year old paternal second cousin with identical irides without mental retardation or ataxia. A paternal great aunt with polycoria, and a paternal great grandmother with a narrow anterior chamber. A paternal first cousin has mental retardation but his eye examination is not known and his status is unclear. This family thus shows a dominant transmission of GS with at least 4 affected members in 4 generations all having isolated iris anomalies including polycoria, narrow anterior chamber except the proband who is the only affected with both iris and cerebellar and mental symptoms. It seems that there are 2 unaffected transmitting males who are obligate carriers and incomplete penetrance in the affected. All reported familial cases are compatible with dominant transmission, the affected sibships could possibly be due to either minimal or non penetrance in one parent or germline mosaicism. Glaser et al 1994 have searched for mutation in the PAX6 gene in 3 families with GS with negative results while Dollfus et al (1998) have reported a patient with GS and a t(X;11)(p22.32;P12) de novo translocation without detectable anomaly in the PAX6 coding sequence.