Mosaic r(13) resulting in large deletion of chromosome 13q in a newborn female with multiple congenital anomalies

Abstract

A newborn female presented with multiple congenital anomalies including facial dysmorphism, agenesis of the corpus callosum, type I laryngeal cleft, tracheal stenosis, bilaterally small kidneys, segmental vertebral anomalies, extranumerary rib, bilateral hip dislocation, digital anomalies, and growth retardation. Newborn aneuploidy detection (NAD) based on interphase fluorescence in situ hybridization (FISH) indicated monosomy 13 in 47 of 200 (23.5%) peripheral blood cells (normal cutoff 8.5% at 95% CI). The follow-up banded metaphase-based analysis of 20 cells revealed a karyotype of 46,XX. The analysis of 30 additional cells revealed one cell to have monosomy 13 and a small ring chromosome. In the abnormal cell line, the ring was positive for whole chromosome paint (wcp) 13 and negative for Rb1 (13q14.3). The ring was detected in 4% of 80 additional metaphases studied by FISH. Therefore, the ring was present in 4% (5/130) of metaphases from peripheral blood. Analysis of buccal cells by FISH indicated the ring was present in 36% of cells. A higher degree of mosaicism (60%) was detected in fibroblast cultures from a skin biopsy. The low-level mosaicism of ring 13 in metaphase cells from peripheral blood would have been missed if the standard 20 GTL-banded metaphases had been analyzed. In this case, a preliminary interphase FISH study had indicated monosomy 13 resulting from a large 13q deletion that included the Rb1 locus. This finding initiated the analysis of additional metaphases by GTL-banding and the analysis of metaphases and interphases by FISH. The clinical presentation of our patient was consistent with reported cases of 13q deletions. In addition, our patient had airway anomalies, including a type I laryngeal cleft and tracheal stenosis, which are previously unreported.

Prenatal Diagnosis of a Case of Partial Monosomy^|^frasl;Monosomy 13 Mosaicism: 46,XX,r(13)(p11q33)^|^frasl;45,XX,-13 Suspected by Nuchal Fold Translucency Increasing

“…A similar phenotype has been noted in 13 ring chromosome patients who were missing part of the short arm as well as part of long arm of chromosome 13 [1][2][3]. Lorentz et al [8] identified four categories of deletion 13q. The first category of the phenotype consisted of mosaic rearrangements that led to 13q deletions.…”

“…The prenatal diagnosis of deletion 13q syndrome is rare [1][2][3][4][5][6][7][8][9][10][11][12]. Deletion 13q syndrome is associated with a wide spectrum of abnormalities, however some of the anomalies in the present case were too faint to be detected by ultrasound tomography.…”

“…The present case falls into the third category as a kind of deletion 13. Deletion of the long arm of chromosome 13 is associated with a wide spectrum of abnormalities, including retinoblastoma, mental and growth retardation, brain malformations, heart defects, distal limb deformities, and digestive, urogenital, and other abnormalities [1][2][3][4][5][6][7][8]. Deletions limited to proximal bands (q32) are characterized mainly by growth retardation but no major deformities.…”

“…Those involving band q32 are usually associated with numerous major malformations, and distal deletions are usually complicated by severe mental retardation with comparatively minor abnormalities. Garcia-Lurie syndrome and this disorder share many common clinical features [1][2][3][4][5][6][7][8][9][10][11][12]. Monosomy 13q3 may arise as a result of a de novo deletion or may occur as a result of abnormal segregation of a parental translocation [13].…”

“…There is no specific treatment. Psychomotor retardation, usually moderate to severe, is always present [1][2][3][4][5][6][7][8][9][10][11][12]. The exact life span is unknown; the oldest patient included in the above survey was 8 years old.…”