Further delineation of the phenotype maps for partial trisomy 16q24 and Jacobsen syndrome by a subtle familial translocation t(11;16)(q24.2;q24.1)

Abstract

We report on two cases of distal monosomy 11q and partial trisomy 16q due to a familial subtle translocation detected by FISH subtelomere screening. Exact breakpoint analyses by FISH with panels of BAC probes demonstrated a 9.3-9.5 megabase partial monosomy of 11q24.2-qter and a 4.9-5.4 megabase partial trisomy of 16q24.1-qter. The index patient displayed craniofacial dysmorphisms, mild mental retardation and postnatal growth retardation, muscular hypotonia, mild periventricular leukodystrophy, patent ductus arteriosus, thrombocytopenia, recurrent infections, inguinal hernia, cryptorchidism, pes equinovarus, and hearing deficiencies. In his mother's cousin who bears the identical unbalanced translocation, mild mental retardation, patent ductus arteriosus, hypogammaglobulinemia, recurrent infections, unilateral kidney hypoplasia, pes equinovarus, and hearing deficiencies were reported. Since only four descriptions of cryptic or subtle partial trisomies 16q have been published to date, our patients contribute greatly to the delineation of the phenotype of this genomic imbalance. In contrast to this, terminal deletions of the long arm of chromosome 11 cause a haploinsufficiency disorder (Jacobsen syndrome) in which karyotype-phenotype correlations are already being established. Here, our findings contribute to the refinement of a phenotype map for several Jacobsen syndrome features including abnormal brain imaging, renal malformations, thrombocytopenia/pancytopenia, inguinal hernia, testicular ectopy, pes equinovarus, and hearing deficiency.

Subtelomeric monosomy 11q and trisomy 16q in siblings and an unrelated child: Molecular characterization of two der(11)t(11;16)

“…In the literature, two other patients with partial 11q monosomy and partial 16q trisomy were reported [Sousa et al, 2004;Zahn et al, 2005]. In both cases, children shared clinical features with ours (Table I).…”

“…In our familial cases (Patients 1 and 2), as in the case described by Zahn et al [2005], the der(11)t(11;16) resulted from the malsegregation of a maternal balanced translocation. In the literature, maternal balanced translocations are frequently the source of 16q trisomies [Sousa et al, 2004], while only 8% of 11qter monosomies would be caused by a parental balanced translocation [Grossfeld et al, 2004].…”

“…Partial 16q trisomy is associated with a wide range of phenotypes. Sousa et al [2004] and Zahn et al [2005] reported on two patients with concomitant 11qter monosomy and 16qter trisomy, resulting from a der(11)t(11;16) [Sousa et al, 2004;Zahn et al, 2005]. In this report, we describe two siblings and an unrelated child with multiple malformations carrying an 11qter monosomy and a 16qter trisomy and characterize the cytogenetic abnormalities.…”

The first case of a patient with de novo partial distal 16q tetrasomy and a data's review

“…While the phenotypic expression of full trisomy 16 is well defined, reports on partial trisomies of distal 16q are rare [Paladini et al, ; Sousa et al, ; Zahn et al, ]. In particular, the phenotypic expression of the terminal 16q24 duplication is largely unknown since only seven cases have been reported to date [Brisset et al, ; Giardino et al, ; Zahn et al, ; Maher et al, ; Joly et al, ; Baker et al, ]. The attempt to define a genotype‐phenotype correlation in this trisomy is even more difficult because all previous cases were unbalanced translocations and the clinical manifestation was a result mainly of partial monosomy rather than trisomy.…”

Paris‐Trousseau‐type macrothrombocytopenia without 11q deletion

“…[9][10][11][12][13][14] PT syndrome is a variant of Jacobsen syndrome in which 11q23.2-qter deletion causes mental and growth retardation, trigonocephaly, facial dysmorphism and malformations of heart, kidney, intestinal system and lower extremities. [15][16][17][18][19][20] The clinical phenotype of previously reported patients with PTJ syndrome varies with the location of the breakpoint. Although giant a-granules in the platelets and bone marrow dysmegakaryopoiesis in the proband suggested PT syndrome, haplotype analysis clearly showed that the entire region between 11q23.3 and 11q24.3 was intact in all of the family members.…”