Atypical Angelman syndrome with macrocephaly due to a familial imprinting center deletion.
Two elderly brothers with severe intellectual disability were diagnosed with Angelman syndrome after a once-removed, 15-year-old cousin was found to have the syndrome due to a deletion of the imprinting center. For many years it was believed the brothers, who both have macrocephaly, were affected by nonsyndromic X-linked mental retardation. This was because, apart from absent speech and intellectual disability, the phenotype of the two men was not characteristic of Angelman syndrome. Conversely, the cousin, in addition to severe intellectual disability, language impairment, and ataxic gait, has microcephaly. None of the three have seizures, and so in the presence of the brothers' macrocephaly, Angelman syndrome was not considered until a diagnosis was made in the younger distant cousin. We report on a familial imprinting center deletion and the importance of considering the mild and atypical Angelman syndrome phenotypes within the differential diagnosis of intellectual handicap, particularly in clarifying the genetic risk to other family members.
Ronan
Anne
A
Hunter Genetics Unit, Waratah, NSW, Australia. anne.ronan@hnehealth.nsw.gov.au
Buiting
Karin
K
Dudding
Tracy
T
D000293:Adolescent; D017204:Angelman Syndrome / Q000175:diagnosis / Q000209:etiology*; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism; D001345:Autoradiography; D001483:Base Sequence; D015139:Blotting, Southern; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15; D005091:Exons; D018392:Genomic Imprinting; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics; D010375:Pedigree; D016133:Polymerase Chain Reaction; D017411:Ribonucleoproteins, Small Nuclear / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D035781:Siblings; D055517:snRNP Core Proteins
D001324:Autoantigens; D009687:Nuclear Proteins; D017411:Ribonucleoproteins, Small Nuclear; C445239:SNURF protein, human; D055517:snRNP Core Proteins