Which genetic phenomena is the most likely diagnosis? A 3-year-old developmentally delayed girl presents to the pediatric neurologist for evaluation of new onset seizures. The parents are also concerned because the child frequently exhibits inappropriate outbursts of laughter. Physical examination is signifi cant for abnormal facies marked by microcephaly, deep-set eyes, and a large mouth with a protruding tongue. The child’s gait is unstable.

Imprinting

The correct answer is C. This child most likely has Angelmans syndrome. Individuals with this phenotype have a characteristic facies with microcephaly, maxillary hypoplasia, deepset eyes, and a large mouth with tongue protrusion. Their gait is jerky and puppet-like, and their behavior is marked by frequent paroxysms of inappropriate laughter. Severe mental retardation and speech impairment are usually present, and 80%90% of patients have epilepsy. Angelmans syndrome, along with Prader-Willi syndrome, is a classic example of imprinting, which occurs when the phenotype differs depending on whether the mutation is of paternal or maternal origin. Deletions in Prader-Willi syndrome, a phenotypically distinct disorder, occur exclusively on the paternal chromosome 15, whereas deletions at the same site of chromosome 15 on the maternal chromosome result in Angelmans syndrome. Answer A is incorrect. Anticipation is the phenomenon in which the severity of a disease worsens in succeeding generations. This occurs, for example, in triplet repeat diseases such as Huntingtons disease, wherein the triplet repeat tends to lengthen, age of onset decreases, and disease severity increases with successive generations. This does not occur in Angelmans syndrome. Answr B is incorrect. Heteroplasmy describes the presence of both normal and mutated mitochondrial DNA. This phenomenon is responsible for the variable expression of mitochondrial inherited diseases. Answer D is incorrect. Locus heterozygosity describes the phenomenon by which mutations at different loci can result in the same phenotype. An example of this is albinism, which can be caused by a number of different mutations. Answer E is incorrect. Mosaicism occurs when cells in the body have different genetic makeup. This sometimes occurs, for example, in Turners syndrome. This does not occur in Angelmans syndrome.