Natural history of 1p36 deletion syndrome: experience with 60 cases. A. Battaglia^1,2, J.C. Carey², H.E. Hoyme³, ICSG. 1) Stella Maris Inst. Pisa, Italy; 2) Medical Genetics, Dept. Pediatrics, University Utah, SLC, USA; 3) Medical Genetics, Dept. Pediatrics, Stanford University, USA.
   From the recent literature it appears that 1p36 deletions account for 0.15-1.2% of idiopathic DD/MR. 1p36 deletion syndrome is a newly recognized segmental aneusomy condition with an estimated incidence of 1/5,000 newborns. Although about 90 cases have been reported so far, there is still little data on its natural history. Information given to parents at the time of diagnosis tends to be skewed to the extreme negative. To help delineate more thoroughly the natural history of monosomy 1p36, and to obtain better information to answer parents questions in a clinical setting, we evaluated 60 patients (female/male ratio: 2/1), in different centers, with the syndrome. One third of them were detected by standard cytogenetics, whereas the other two thirds by subtelomeric FISH analysis. OFC was at/below the 2 centile, and height/weight ranged between <3rd-50th centile. All patients had a distinct craniofacial appearance with tower skull, prominent forehead, deep-set eyes, straight eyebrows, epicanthus, midface hypoplasia, broad nasal root/bridge, long philtrum, pointed chin; associated with brachy/camptodactyly, and short feet. 70% of the patients had CNS anomalies (ventricular dilatation; cortical atrophy; multifocal white matter T2 hyperintensity); 70% had heart defects (ventricular myocardium non-compaction [n=15]; ASD; VSD; PDA; tetralogy of Fallot); 50% had seizures (infantile spasms; partial and generalized seizures); 40% had hearing impairment; 40% had skeletal anomalies; 100% had mild/profound DD/MR, and 95% had hypotonia. 80% had no speech, whereas the remaining 20% pronounced either isolated words or simple words associations. Just over 25% was able to walk alone, and 70% had a behavior disorder. A slow, but constant progress in development was observed in all cases overtime. The non-compaction of the ventricular myocardium, and all seizure types were well controlled by the usual pharmacotherapy. In conclusion, the combined cases of our sample represent considerable experience, providing new information on several aspects of this important and frequent deletion syndrome.