Angelman syndrome with uniparental disomy due to paternal meiosis II nondisjunction

We report a case of Angelman syndrome (AS) with paternal uniparental disomy (pUPD) of chromosome 15. This 6-year-old girl with overgrowth had frequent , but only provoked laughter, was mildly ataxic with limb hypertonia, and h ad no intelligible speech. She had deep-set eyes, protruding tongue, and pr ominent chin. The karyotype was normal. DNA analysis with microsatellites f rom chromosome 15 showed no inheritance of maternal alleles both within and outside the AS critical region. Proximal markers showed reduction to homoz ygosity of paternal alleles, intermediate markers showed nonreduction, and distal markers reduction, thus suggesting a meiosis II nondisjunction event in the father with two crossovers. This is, to our knowledge, the first re ported case of AS due to meiosis II nondisjunction. We present detailed phy sical measurements in this patient, adding to the clinical description of t he milder phenotype in AS due to pUPD.