Abstracts

RATIONALE: There have been several studies aimed at clarifying the genotype-phenotype correlations in patients with inverted duplication of chromosome 15 [inv dup (15)], which is usually characterized by severe mental retardation and epilepsy in individuals with large duplications including the Prader-Willi/Angelman region. We report two patients with inv dup (15) whom, in spite of a large duplication, presented with a mild phenotype including adult onset epilepsy. This report may help defining the milder spectrum of the syndrome.
METHODS: A 25-year-old girl, had a 6-year history of absence seizures, with occasional head drop and mild mental retardation. Interictal EEG revealed diffuse sharp-wave complexes. Epilepsy was well controlled by an association of lamotrigine and valproate. The other patient, a 27 year-old man, had a 5-year history of rare generalized tonic clonic seizure during sleep, and frequent episodes of urensponsiveness. Two latter seizures were captured during EEG recording and were accompanied by generalized rhythmic slow spike and wave discharges, indicating atypical absence seizures. An association of valproate and lamotrigine lead to a remarkable improvement, although no complete seizure control.
RESULTS: Molecular analysis revealed a large inv-dup 15 extending to band q14 with tetrasomy of 15q11q14 and band q15 in the two patients, respectively.
CONCLUSIONS: The discrepancy between the very mild phenotype and the severe chromosomal abnormality detected in these two patients further supports the notion that the site of breakpoint might be contributory to the inv dup(15) phenotype. It also suggests that such a diagnosis should be considered in atypical cases of generalized epilepsy of adult-onset without clear-cut etiology.