Clinical and molecular characterization of an infant with a tandem duplication and deletion of 19p13

Abstract

Copy number variations (CNVs) on the short arm of chromosome 19 are relatively rare. We present a patient with a tandem de novo 3.9 Mb duplication of 19p13.12p13.2 and an adjacent 288 kb deletion of 19p13.12. The CNVs were detected by genome wide SNP-array and confirmed by fluorescence in situ hybridization. Mate-pair sequencing revealed two breakpoint junctions leading to a germline tandem inverted duplication and an adjacent deletion. The patient had a major congenital heart defect and refractory edema leading to metabolic and endocrinological disturbances. Further complications occurred due to refractory chylothorax, severe inflammatory response syndrome, and repeating sepsis. After 2 months, the child died due to intractable respiratory failure. The phenotype of this patient was compared with reported patients with overlapping deletions or duplications. We conclude that the congenital heart defect, respiratory insufficiency, and abnormal neurologic examination are most likely due the contiguous gene deletion/duplication.

Etiological factors and treatment of chylothorax in paediatric patients - a systematic review

“…[49], [51-52], [54-58], [60-64], [66], [70][71][72][73][74][75][76][77][78][79][80][81], [84][85][86][87][88], [90][91][92][93], [95][96][97][98][99][100][101][102][103].…”

“…It is possible to achieve such a result by introducing dietary supplements containing medium chain triglycerides (MCT) or starting the patient on a total parenteral nutrition (TPN) [5], [82], [83]. As much as 33.7 % of children from the reviewed literature was treated with the first of the abovementioned methods [2], [17], [19], [23], [25], [33], [40], [40], [43], [52], [56], [72], [77], [79], [81], [84]- [89]. It is preferred mainly in patients with normal circulatory and respiratory function [5].…”

“…Dietary modifications are often used interchangeably or synergistically in case of a failure of one of the treatment methods. One of the more common dietary modifications is implementation of first MCT, and then TPN as a second line of treatment (19,6 %) [2], [19], [25], [56], [79], [84]. Occasionally, the authors did not precisely indicate which treatment -MCT or TNP was prescribed [28], [35], [39], [43], [62], [63],…”

“…In the event of chyle infection in the pleural cavity, antibiotic therapy is initiated [17], [41], [66], [75]. Intravenous steroids are also frequently administered in order to reduce inflammation [19], [25], [32], [62], [72], [79], [80], [84], [87], [103]. Antithrombotic prophylaxis, involving heparin -mainly low molecular weight heparin, enoxaparin [71], [72], [95].…”

A recognizable phenotype related to 19p13.12 microdeletion

“…The chromosome 19 has the highest gene density among the human chromosomes (Grimwood et al, ). Microdeletions at 19p13.12 have been reported in few patients (Engels et al, ; Jensen et al, ; Van Der Aa et al, ; Bonaglia et al, ; Kosaki et al, ; Gallant et al, ; Jelsig et al, ; Dale et al, ; Tan et al, ). The phenotypes vary according to deletion sizes, but includes mainly mild to moderate intellectual disability, cardiac malformations, brain malformations, sensorineural deafness, pre‐auricular tags, stenosis of external ear canals, hypertrichosis, and synophrys (Jelsig et al, ).…”