A case of de novo duplication of 15q24-q26.3

Abstract

Distal duplication, or trisomy 15q, is an extremely rare chromosomal disorder characterized by prenatal and postnatal overgrowth, mental retardation, and craniofacial malformations. Additional abnormalities typically include an unusually short neck, malformations of the fingers and toes, scoliosis and skeletal malformations, genital abnormalities, particularly in affected males, and, in some cases, cardiac defects. The range and severity of symptoms and physical findings may vary from case to case, depending upon the length and location of the duplicated portion of chromosome 15q. Most reported cases of duplication of the long arm of chromosome 15 frequently have more than one segmental imbalance resulting from unbalanced translocations involving chromosome 15 and deletions in another chromosome, as well as other structural chromosomal abnormalities. We report a female newborn with a de novo duplication, 15q24-q26.3, showing intrauterine overgrowth, a narrow asymmetric face with down-slanting palpebral fissures, a large, prominent nose, and micrognathia, arachnodactyly, camptodactyly, congenital heart disease, hydronephrosis, and hydroureter. Chromosomal analysis showed a 46,XX,inv(9)(p12q13),dup(15)(q24q26.3). Array comparative genomic hybridization analysis revealed a gain of 42 clones on 15q24-q26.3. This case represents the only reported patient with a de novo 15q24-q26.3 duplication that did not result from an unbalanced translocation and did not have a concomitant monosomic component in Korea.

Partial trisomy 15q23 and partial monosomy 5p15.32: Case report and a literature review

“…Distal trisomy, or duplication of 15q, is an extremely rare chromosome disorder. Initially described by Fujimoto et al [], duplication of 15q syndrome has now been reported in at least 50 cases [Kim et al, ]. Deletion 5p syndrome, cri du chat syndrome (CdCS) is clinically well defined.…”

“…Clinical features of distal trisomy 15q include: prenatal and postnatal overgrowth, psychomotor developmental delay, craniofacial malformation (microcephaly, broad forehead, craniosynostosis, downslanting palpebral fissures, short neck, broad nasal bridge, long philtrum, high palate, low‐set ear, micrognathia), pectus excavatum, malformations of fingers and toes (arachnodactyly, camptodactyly, shortened thumb, broad 1st toe), cryptorchidism, and cardiac defects. Of particular interest, insulin‐like growth factor 1 receptor ( IGF1R ) gene located on 15q26.3 which has been implicated in pre‐ and postnatal growth [Baker et al, ; Tatton‐Brown et al, ; Kim et al, ]. Overgrowth and macrocephaly have been casually related to a dosage excess of IGF1R gene in patients with trisomy 15q [Baker et al, ; Church et al, ; Nagai et al, ; Faivre et al, ; Kim et al, ].…”

“…Of particular interest, insulin‐like growth factor 1 receptor ( IGF1R ) gene located on 15q26.3 which has been implicated in pre‐ and postnatal growth [Baker et al, ; Tatton‐Brown et al, ; Kim et al, ]. Overgrowth and macrocephaly have been casually related to a dosage excess of IGF1R gene in patients with trisomy 15q [Baker et al, ; Church et al, ; Nagai et al, ; Faivre et al, ; Kim et al, ]. Overgrowth is rarely seen with chromosomal anomalies.…”

Acute leukemia in a patient with 15q overgrowth syndrome

“…A review of PubMed references for cases of trisomy and tetrasomy of the region distal to 15q25 revealed 29 individuals of a wide range of ages. (Kim et al, ; Tatton‐Brown et al, ). With the addition of this report, there are two malignancies among 30 reported 15q OGS individuals.…”

Refining critical regions in 15q24 microdeletion syndrome pertaining to autism

“…The smallest region of overlap has been predicted to be an approximately 1.2-Mb region between 15q24B and 15q24D as a majority of 19 patients with 15q24 deletions involved in this region (Magoulas & El-Hattab, 2012;McInnes et al, 2010;Mefford et al, 2012aMefford et al, , 2012b. So far, more cases with 15q24 deletions and duplications have been reported to present common clinical features (Roggenbuck et al, 2004;Miller et al, 2005;Schluth et al, 2005;Andrieux et al, 2009;El-Hattab et al, 2010;Roetzer et al, 2010;Cukier et al, 2011;Kim et al, 2011;O'Connor et al, 2011;Huynh et al, 2018;Ochando et al, 2018;Mefford et al, 2012b;Siu et al, 2016). To increase the number of cases, we searched all the literature, DECIPHER, and ClinGen databases for 15q24 deletions and duplications.…”