Summary: Purpose: Several studies attempted to clarify 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) who, in spite of a large duplication, had a mild phenotype including adult-onset epilepsy. This report may help to define the milder spectrum of the syndrome.
Methods: A 25-year-old girl with mild mental retardation had a 6-year history of absence seizures, with occasional head drop. Interictal EEG revealed diffuse spike–wave complexes. Epilepsy was well controlled by a combination of lamotrigine (LTG) and valproate (VPA). The other patient, a 27-year-old man with mild mental retardation, had a 5-year history of rare generalized tonic–clonic seizure during sleep, and frequent episodes of unresponsiveness, which appeared to be atypical absence seizures on video-EEG recordings. A combination of VPA and LTG led to a remarkable improvement, although no complete control.
Results: Molecular analysis revealed a large inv dup15 in both patients.
Conclusions: The discrepancy between the 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. Inv dup(15) should be considered in atypical cases of generalized epilepsy of adult onset without clear-cut etiology.