Reciprocal 1;17 translocation in a patient with apparent Aicardi syndrome plus complex congenital heart disease and limb malformation. M.C. Prieto1, S. Khan1, C. Tuck-Muller1,3, S. Li1,3, R. Gordon2, M. Marble1. 1) Human Genetics Program, SL31, Tulane Univ Medical Ctr, New Orleans, LA; 2) Department of Ophthalmology, Tulane University Medical Ctr, New Orleans, LA; 3) Department of Medical Genetics, University of South Alabama, Mobile, AL.
We present a 3-month-old girl with microphthalmia, chorioretinal lacunae, vertebral malformations, total agenesis of the corpus callosum, Dandy Walker anomaly, EEG abnormalities, limb defect and congenital heart disease (single left ventricle with AV canal). Most of these findings are indicative of Aicardi syndrome, an X-linked disorder mapping to Xp22. However, congenital cardiac anomalies and limb abnormalities are not part of Aicardi spectrum. Chromosome analysis revealed an apparently balanced de novo reciprocal 1;17 translocation. C-banding confirmed the breakpoint in chromosome 1, and the heterochromatic band of chromosome 1 was split between the derivative 1 and the derivative 17. Fluorescence In Situ Hybridization (FISH) using DNA probes (from Oncor, Inc.) specific for Smith-Magenis (D17S258) and Miller-Dieker (D17S379) regions confirmed the breakpoints in chromosome 17. The STS probe (Oncor, Inc.), specific for the steroid sulfatase region (Xp22.3) which maps close to but distal to the Aicardi locus, hybridized to both X chromosomes. The karyotype was determined to be 46,XX,t(1;17)(q12;p12).ish t(1;17)(q12;p12)(D17S379+;D17S258+,D17S379-),Xp22.3(STSx2). In conclusion, our patient has the typical features of Aicardi syndrome but also has a complex congenital heart disease and a limb abnormality. We speculate that the apparently balanced 1;17 translocation may have a submicroscopic imbalance causing Aicardi-like features with additional anomalies. Alternatively, our patient may have Aicardi syndrome due to an X-linked mutation and the heart and limb anomalies due to the translocation.