Unbalanced cryptic 5p deletion/17p duplication identified by subtelomeric FISH in a family with a boy with chimerism and a balanced t(4;5)

Abstract

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 balanced t(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.

Cri du Chat syndrome

“…FISH revealed that five of these patients had an interstitial deletion, one had a small terminal deletion and one had mosaicism [ 56 ]. Subtelomeric FISH allows 5p cryptic chromosomal rearrangements to be found [ 34 , 82 ]. Recent techniques, such as array CGH and quantitative PCR, mainly used for research purposes, allow a more precise definition of breakpoints and microrearrangements [ 77 - 79 ].…”

Cryptic unbalanced translocation t(17;18)(p13.2;q22.3) identified by subtelomeric FISH and defined by array‐based comparative genomic hybridization in a patient with mental retardation and dysmorphic features

“…While this specific cryptic unbalanced rearrangement has not been reported previously, deletions of 18q have been well described [Kline et al, 1993; Strathdee et al, 1995; Hale et al, 2000; Gunn et al, 2003]. Our patient with a deletion of 18q22.3‐qter presents a typical 18q‐deletion syndrome (Table II), but she has some findings consistent with the described 17p trisomies including telecanthus, microcephaly, developmental delay, postnatal growth retardation, a short webbed neck, and congenital heart defect [Lurie et al, 1995; Ensenauer et al, 2004] (Table III).…”

Evidence for involvement of TRE-2 (USP6) oncogene, low-copy repeat and acrocentric heterochromatin in two families with chromosomal translocations

“…Isolated duplications of this genomic region have not been described yet. Recently, Ensenauer et al (2004) and Hwang et al (2005) reported duplication of the MDLS region due to unbalanced translocations t(5;17)(p15.31;p13.1) and Fig. 3 a Partial G-banded karyotype for chromosome 17 in family 2 with arrow indicating the der (17) chromosome.…”