A t(5;16)(p15.32;q23.3) generating 16q23.3 → qter duplication and 5p15.32 → pter deletion in two siblings with mental retardation, dysmorphic features, and speech delay

Abstract

We report on two siblings (half brothers on the paternal side) with a syndrome consisting of delayed development, cardiac anomalies, chest deformity, hip rotation, metatarsus adductus, genital hypoplasia, dysmorphic face, depressed nasal bridge, mental retardation, and speech delay. All metaphases examined showed a normal karyotype in the patients, their father, and both mothers. High-resolution array CGH examination revealed a 16q (6 Mb) duplication dup(16)(16q23.3 --> 16qter) and a 5p (0.97 Mb) terminal deletion del(5)(p15.32 --> pter) in both affected boys but not their healthy siblings or parents. Interphase fluorescence in situ hybridization (FISH) confirmed both the 16q duplicated region and the 5p terminal deletion. Clinical abnormalities in the patients included thin upper lip, clinodactyly, and foot deformity, which were reported previously with duplications in 16q23.3. Pectus excavatum, hip rotation, metatarsus adductus, umbilical hernia, brachycephaly, and esotropia were not reported previously in chromosome 16q duplications but may be features that occur intermittently. The 5p deleted region has been associated previously only with speech delay, which was present in both patients. These patients display certain phenotypic characteristics not reported previously in 16q duplication and confirm 5p terminal deletion as an important chromosome anomaly for speech delay.

A small de novo 16q24.1 duplication in a woman with severe clinical features

“…Interestingly, three cases that were reported are phenotypically similar to our patient [4,8,10]. The first one was a t(16;22)(q24;q13.3) with a 22q deletion/16q duplication.…”

“…Because the phenotype of our case was less severe, we looked at 16q duplications that were closer to our region with breakpoints located between 16q21 and 16q24.3 [7,9,13]. When considering duplications with 5' breakpoints located between 16q21 and 16q23, Houlston et al [7] found similarities in patients facial features (a prominent forehead, midface hypoplasia and downward slant) and an association with intellectual disability, muscular hypotonia, congenital heart defects, failure to thrive, genitalia hypoplasia, periorbital edema, palpebral fissures and umbilical hernia [8][9][10]. Involvement of the 16q24 band causes similar characteristics, suggesting that some symptoms, such as developmental delay, cardiac defects, small palpebral fissures, periorbital edema, hypotonia, long fingers, recurrent infections, epicanthal folds broad/flat nasal bridge and high arched palate, may be related to the 16q24 → qter region [4,11,12].…”

“…The patient had a severe psychomotor/developmental delay with no speech, large nose and hyperextensibility of joints [8]. The other patients were carriers of a t(7;16)(p22.3;q24.1) with a 7p deletion/16q duplication and a 16q23.3 → qter duplication/5p15.32 → pter deletion, respectively [4,10]. Among their features, they shared some characteristics with our patient: severe psychomotor retardation, hypotonia, long fingers, broad nasal bridge, high forehead, high-arched palate, epicanthal folds and malformed ears.…”

“…Here, we report a woman with a small de novo duplication of 250 kb in the 16q24.1 region detected by chromosomal microarray and confirmed by quantitative fluorescence multiplex-PCR (QFM-PCR). Because our patient's clinical features are particularly severe considering the size of the duplication, we compared her phenotype with previously described cases of 16q trisomy [4][5][6][7][8][9][10][11][12][13]. Small chromosomal rearrangements such as the one found in this case may help to delineate the contribution of selected genes in larger 16q duplications.…”

Clinical and molecular findings in 39 patients with KBG syndrome caused by deletion or mutation of ANKRD11

“…From the literature, only four deletions include SPG7 which is located very close to ANKRD11 . Interestingly, visible 16qter cytogenetic deletions have never been reported whereas several cases of 16qter duplications as consequences of unbalanced chromosomal rearrangements have been described [Zou et al, ; Hellani et al, ]. Importantly, this finding suggests that haploinsufficiency of 16qter distal to ANKRD11 could be lethal.…”