Trisomy 8q and partial trisomy 22 in a 43‐year‐old man with moderate intellectual disability, epilepsy and large cell non‐Hodgkin lymphoma

Abstract

Partial trisomies are chromosome abnormalities resulting in a broad range of malformations depending on the size and location of the chromosomal rearrangement. Whereas diagnosis of these syndromes is usually made in early childhood, few descriptions exist about the clinical picture in adulthood. We report on a patient diagnosed at the age of 43 years with a 47,XY,+der(22)t(8;22)(q24.13;q11.21) karyotype and predominant clinical features of trisomy 8q. To our knowledge, this is the oldest patient described with a partial trisomy 8. The patient presented with moderate intellectual disability, a past history of epilepsy and facial anomalies. In addition, a large cell non-Hodgkin lymphoma was diagnosed in adulthood. Detailed breakpoint mapping by single nucleotide polymorphism (SNP) arrays showed that the derivative chromosome contains a full-length copy of the C-MYC oncogene. Given that trisomy 8q is the most frequent secondary chromosomal abnormality in hematological diseases, the possibility of a genetic predisposition for these disorders in patients with 8q duplication is raised.

A Palindrome-Mediated Recurrent Translocation with 3:1 Meiotic Nondisjunction: The t(8;22)(q24.13;q11.21)

“…[26][27][28][30][31][32][33][34][35] Several of these reports indicated gross molecular positioning of the 8q and 22q breakpoints consistent with what would be predicted on the basis of our two cases. We subsequently received samples from two patients carrying the supernumerary der( 22)t(8;22) 26,27 and a father-daughter pair who are t(8;22) balanced carriers 28 and have performed additional analyses. As predicted, the breakpoints are identical by FISH (patient 8) 26 or SNP array (patient 9; Figure 1).…”

“…Genomic DNA was extracted from peripheral blood or lymphoblast cell lines via previously described methods. 23,[26][27][28] Nested PCR was performed with the use of the primers described in Gotter et al 23 Primer sequences are available in Table S1, available online. In brief, der(8) products were amplified with the use of the following primers: primary amplification: 8q24-7F with 22.B2R; secondary amplification: 8q24-8F with 22.B4R; der(22) product amplification: primary amplification: 22.B1 and 8q24-7R, secondary amplification: 22.B3 and 8q24-8R.…”

“…As predicted, the breakpoints are identical by FISH (patient 8) 26 or SNP array (patient 9; Figure 1). 27 PCR plus sequencing of the der(8) and der( 22) junction fragments indicates that all of the breakpoints are localized in the PATRRs (Figures 2A and 2B; patients 8, 9, 16, and 17). Interestingly, although the nucleotide sequence of the individual junction fragments is nearly identical, they are each unique.…”

“…Interestingly, patient 9, the oldest patient in this study, was reported to have epilepsy and was diagnosed with large-cell non-Hodgkin lymphoma. 27 Thus, although the supernumerary der(22)t (8;22) phenotype is variable between individuals, it tends to include ear and extremity abnormalities in addition to mild mental retardation.…”

Trisomy 8 Mosaicism and Favorable Outcome After Treatment of Infantile Spasms: Case Report

“…11,13,14 One report describes a patient with epilepsy, who was diagnosed with constitutional mosaic trisomy 8 syndrome in adulthood but who reportedly had seizure onset in infancy. 15 Published data suggest a variable response to antiepileptic medications. In one reported case, zonisamide was effective for astatic and generalized seizures but not for complex partial seizures, which was refractory to zonisamide, clonazepam, and carbemazepine.…”