Unique double de novo structural rearrangements for chromosome 11 with 46,XX,del(11)(q13q23)/46,XX,inv dup(11)(q13q23) in an infant with minor congenital abnormalities and delayed development

Reported here is a patient with two most unusual structural rearrangements, both involving chromosome 11. The first cell line showed an interstitial deletion of a chromosome 11 with a 46,XX,del(11)(q13q23) chromosome complement. In the second cell line, one of the chromosome 11s had a duplication for the exact region, (11)(q13q23), that was deleted in the first cell line. This duplication also appeared to be inverted with karyotype 46,XX,inv dup(11)(q13q23). Interestingly, chromosome analysis did not reveal a normal cell line and the two abnormal cell lines were present in a 1:1 ratio. Parental chromosome analyses showed normal karyotypes. The patient was referred for genetic evaluation because of developmental delay. Minor congenital anomalies presented on physical examination included: weight and height at or below the 5th percentile, microcephaly, downward slanting palpebral fissures, severe clinodactyly of one toe, bilateral short fifth fingers and a broad based gait. Results of the MRI and urine metabolic screen were normal. Two hypotheses are advanced to explain the origin of the abnormality. It is most likely that the abnormality arose as a postzygotic event at the very early zygotic division. During the first DNA synthesis after fertilization and before the zygotic division, DNA synthesis errors could resultmore » in two chromatids, one with a deletion and the other with a duplication. It is also possible that after the DNA synthesis prior to the first cell division, the chromatids of the same chromosome 11 for unknown reasons were involved in uneven double somatic crossing over events resulting in deleted and duplicated chromatids, respectively. The 1:1 cell ratio found in the patient and the apparent non-existence of a normal cell line further suggest that the origin of the abnormality was post-zygotic.« less