Partial tetrasomy 15 syndrome due to a bisatellited isochromosome

A 5-year-old boy of Arabian descent was karyotyped because he had moderate mental retardation, severe speech retardation, hyperactivity, strabismus, and an abnormal EEG. Three cell lines were identified in preparations of 104 cells obtained from peripheral blood cultures. A normal karyotype was observed in 30 cells; 54 cells had an extra E-group-sized submetacentric chromosome with satellites on both the long and short arms. The remaining 20 cells each had, in addition to the first marker (M1), a second bisatellited chromosome (M2) which was the smallest chromosome in the karyotype. This smaller marker was morphologically similar to the small extra bisatellited chromosomes seen occasionally in phenotypically normal individuals. Since both ends of M1 and M2 were satellited and participated in acrocentric associations, the markers were derived from one or more acrocentric chromosomes. C-banding demonstrated that both markers were dicentric. However, M1 had only one primary constriction. Therefore one centromere was apparently inactive, analogous to that seen in certain tandem X-X translocations and X isochromosomes. Although low frequency mosaicism cannot be excluded, the parents did not appear to carry either marker. Genotyping and karyotyping data were consistent with paternity. We therefore suggest that the dicentric M1 was derived from meiotic breakage and sister chromatid fusion in the proximal long arm of an acrocentric chromosome. This would have produced a symmetric isodicentric chromosome, plus 1 or 2 acentric fragments. M2 then could have resulted from a dicentric bridgebreak-synthesis-reunion phenomenon. G-, C-, and Q-banding data are consistent with the isodicentric having originated from a chromosome 15. Similar phenotypic and karyotypic findings have been described in 3 other patients. In 2 patients a bisatellited chromosome indistinguishable from our M1 was observed in all of 30 metaphases, but was interpreted as having originated from a translocation between a chromosome 15 and another acrocentric. In one patient the extra chromosome was said to represent a trisomy for the proximal half of chromosome 15. All 4 subjects had normal height, weight, and head circumference. Abnormalities present were hyperactivity (4/4), mental retardation (4/4), abnormalities of speech (3/3), strabismus (3/4), EEG abnormalities (3/3), increased number of ulnar loops (2/3), and hypotonia (2/3). The frequency of this partial tetrasomy 15 syndrome may be greater than presently recognized because individuals with mental retardation in association with a superfically normal phenotype are frequently not karyotyped.