Unbalanced Cryptic 5p Deletion/17p Duplication Identified by Subtelomeric FISH in a Family with a Boy with Chimerism and a Balanced t(4;5)

The use of subtelomeric FISH probes has greatly supplemented conventional chromosome analysis in detecting cryptic anomalies in patients with mental retardation (MR), dysmorphic features, and congenital malformations. We report a 3-month-old boy who was diagnosed with ambiguous genitalia, dysmorphic features, and developmental delay. Standard chromosome studies on blood revealed a chimeric karyotype of 46,XY,t(4;5)(q31.1;q14)[46]/46,XX[4]. The boy had intra-abdominal gonads that were testicular in origin by biopsy. Multiple dysmorphic features, marked hypotonia, developmental delay, poor growth, and relative macrocephaly were noted on physical exam. His 2.5-year-old sister also presented with hypotonia, developmental delay, relative macrocephaly, and similar dysmorphic stigmata. In addition, she was diagnosed with several internal malformations. Her karyotype was 46,XX. Due to the striking phenotypic similarity, subtelomeric FISH studies were initiated in the siblings. In addition to the known balanced karyotypic abnormalities, the boy was found to have a derivative chromosome 5 with a 5pter deletion and a 17pter duplication. This cryptic abnormality was also detected in his sister. Chromosome analysis of the father revealed a subtle balancedt(5;17)(p15.31;p13.1) which was confirmed by subtelomeric FISH, whereas the mother's chromosome complement was normal. This familial constellation illustrates the usefulness of subtelomeric FISH in the diagnosis of cryptic chromosome abnormalities in patients for whom conventional karyotype does not disclose findings sufficient to explain the observed phenotypic anomalies.