Available online at www.annclinlabsci.org 332 Annals of Clinical & Laboratory Science, vol. 43, no. 3, 2013 Clinical and Cytogenetic Features of a Patient with Partial Trisomy 8q and Partial Monosomy 13q Delineated by Array Comparative Genomic Hybridization Young Bae Sohn1, Jun No Yun1, Sang-Jin Park2, Moon Sung Park3, Sung Hwan Kim3, and Jang Hoon Lee3 1Department of Medical Genetics, Ajou University School of Medicine, Suwon; 2MG MED, Inc., Seoul; and 3Department of Pediatrics, Ajou University School of Medicine, Suwon, Korea Abstract. Partial trisomy 8q is rare and has distinctive clinical features, including severe mental retardation, growth impairment, dysmorphic facial appearances, cleft palate, congenital heart disease, and urogenital anomalies. Partial monosomy 13q is a rare genetic disorder displaying a variety of phenotypic characteristics including mental retardation, dysmorphic facial features, and congenital anomalies. Here, we describe for the first time clinical observations and cytogenetic analysis of a patient with a concomitant occurrence of partial trisomy of 8q (8q21.3→qter) and partial monosomy 13q(13q34→qter). The patient was a female neonate with facial dysmorphia, agenesis of the corpus callosum, cleft palate, and congenital heart disease. G-band standard karyotype was 46,XX,add(13)(q34). To determine the origin of additional genomic gain in chromosome 13, array comparative genomic hybridization (CGH) was per- formed. Array CGH showed a 56.8 Mb sized gain on chromosome 8q and a 0.28 Mb sized loss on chromo- some 13q. Therefore, the final karyotype of the patient was defined as 46,XX, der(13)t(8;13)(q21.3;q34). In conclusion, we described the clinical and cytogenetic analysis of the patient with concomitant occurrence of partial trisomy 8q and partial monosomy 13q delineated by array CGH. This report suggests that the ar- ray CGH would be a valuable diagnostic tool for identifying the origin of small additional genetic materials. Key words: partial trisomy 8q, partial monosomy 13q, Array CGH Introduction and 2 are characterized by severe intellectual dis- abilities, growth retardation, and congenital mal- Partial trisomy 8q is rare and has distinctive clinical formations of the brain, eyes, and extremities, as features, including severe mental retardation, well as of the gastrointestinal and/or genitourinary growth impairment, dysmorphic facial features systems. However, most of the patients with the (prominent forehead, down-slanting palpebral fis- Group 3 deletion have only intellectual disabilities, sures, hypertelorism, a depressed nasal bridge, low- and rarely experience growth retardation or other set malformed ears, a long philtrum, microgna- major malformations [4,6]. thia), cleft palate, congenital heart disease, and urogenital anomalies [1-3]. A concomitant occurrence of partial trisomy of 8q (8q21.3→qter) and partial monosomy of 13q Patients with 13q deletion have varied phenotypi- (13q34→qter) has not been previously described. cal features [4,5]. The 13q deletion syndrome is divided into three groups based on the location of Chromosome analysis by standard G-banding the deletion: the deletion of chromosome region karyotyping is a major diagnostic tool for patients proximal to 13q32 (group 1), distal deletion in- with congenital malformations, developmental de- cluding at least a part of 13q32 (group 2), and lays, birth defects and mental retardations [7]. distal deletion of 13q33-34 (group 3) [5]. Groups 1 However, small structural abnormalities of chro- mosomes, including small excessive chromosomal Address correspondence to Jang Hoon Lee; Department of Pediatrics, Ajou University School of Medicine, San 5, Wonchun-dong, segments or a marker chromosome, cannot be re- Yeongtong-gu, Suwon, 443-721, Korea; phone: +82 31 219 5165; fax: +82 31 219 4521; e mail: [email protected] solved only by conventional G-banded analysis [8]. 0091-7370/13/0300-332. © 2013 by the Association of Clinical Scientists, Inc. A patient with partial trisomy 8q and partial monosomy 13q 333 Array comparative genom- ic hybridization (Array CGH) has been described as an additional method for identifying the origin of small genetic abnormal- ities [7,9-11]. Moreover, because the array CGH test does not require cell culture (as conventional chromosome analysis does), a clinician could get the test results faster. Here, we report the clini- cal and cytogenetic fea- tures of a patient with con- comitant partial trisomy 8q and partial monosomy 13q diagnosed by standard karyotyping and addition- al array CGH. This is, to the best of our knowledge, the first report of concom- itant partial trisomy 8q and partial monosomy Figure 1. Abnormal morphologic feature showing crumpled ear, hypertelorism, micrognathia, 13q in a patient. and overlapping fingers and toes Materials and Methods was suspected by trans-abdominal ultrasonography at antenatal periods. Apgar scores at one and five Clinical evaluations. The assessment of physical growth was minutes were 7 and 8 respectively. At birth, weight evaluated by Korean reference data [12]. Laboratory tests in- cluding complete blood cell count (CBC), serum AST/ALT, was 2960 g (10-25 percentile), height was 47.4 cm BUN/creatinine, blood glucose, triiodothyronine (T3), free (10-25 percentile), and head circumference was 35 thyroxine (free T4), and thyroid-stimulating hormone (TSH) cm (75-90 percentile). Abnormal morphological were performed. Brain magnetic resonance imaging (MRI) was features included crumpled ear, hypertelorism, mi- performed to investigate brain anomalies. Echocardiography was performed to evaluate cardiac morphology and function. crognathia, cleft palate, and overlapping fingers and toes (Figure 1). Laboratory tests were normal: Cytogenetic analysis. Chromosome analysis was performed on WBC 10800/µl Hb 16.3 g/dl 232 x 103/µl, AST/ cultured lymphocytes from peripheral blood by examination of ALT 25/42 U/L, BUN/creatinine 6.8/0.7 mg/dl, 20 G-banded metaphase cells. For array CGH, DNA was ex- blood glucose 74 mg/dl, T3 86 ng/dl, free T4 1.17 tracted from peripheral blood using the PureGene kit (Gentra Systems, Inc., Minneapolis, MN). Slides containing 1440 hu- ng/dl, and TSH 4.49 uIU/ml. Neonatal tandem man BAC (Bacteral Artificial Chromosomes) clones were used mass screening tests were normal. Agenesis of the at an average resolution of 2.3 Mb for the entire genome. corpus callosum was diagnosed upon brain MRI (Figure 2). Perimembranous ventricular septal de- Results fect (VSD), secondum type atrial septal defect, and patent ductus arteriosus (PDA) were diagnosed Clinical findings.A female neonate was born at 40 with echocardiography. Abdominal sonogram re- weeks’ gestation as the first child of healthy, non- vealed no urogenital anomalies. At 37 days after consanguineous Korean parents. Her mother had birth, patch repair of VSD and ligation of PDA no history of health problems including spontane- were performed due to aggravated symptoms in- ous abortion. Fetal agenesis of the corpus callosum cluding dyspnea, oxygen dependency, and feeding 334 Annals of Clinical & Laboratory Science, vol. 43, no. 3, 2013 Figure 2. Brain MRI showing agenesis of corpus callosum (arrows). intolerance irresponsive to medical treatment. Discussion Although dyspnea and oxygen dependency were improved after heart surgery, feeding intolerance In this report, we describe for the first time, to our (uncoordination of sucking and swallowing) con- knowledge, clinical and cytogenetic findings of a tinued up to hospital discharge with orogastric tube patient with concomitant occurrence of partial tri- feeding. somy 8q and partial monosomy 13q. Cytogenetic findings.The initial standard chromo- Full trisomy 8, or Warkany syndrome, has severe some study revealed 46,XX,add(13)(q34) karyo- effects on the developing fetus and is almost always type (Figure 3). To delineate the origin of addition- perinatally lethal. Mosaic trisomy 8 syndrome is al genomic gain in chromosome 13, array CGH less severe, and individuals with this condition are was performed. Array CGH showed a region of more likely to survive and have distinct clinical gain spanning approximately 56.8 Mb on chromo- characteristics including mental retardation, spe- some 8q and a region of loss of approximately 0.28 cific facial features (prominent forehead, deep-set Mb on chromosome 13q (Figure 4). Because the eyes, strabismus, hypertelorism with broad nasal terminal deletion size of 13q was very small, we root, micrognathia, high arched palate, cleft palate, confirmed the deletion by fluorescence in situ -hy and prominent cupped ears with thick helices), bridization (FISH) analysis with 13q34 probe joint contractures, vertebral anomalies, narrow pel- (D13S1009). The FISH analysis showed deletion vis, ureteral-renal anomalies, and other anomalies of 13q34 (Figure 5). Therefore, the final karyotype [13]. Partial trisomy 8q is less well-defined, with of the patient was 46,XX,der(13)t(8;13) relatively few patients described [3,14,15] since (q21.3;q34). The patient has both a partial trisomy Lejeune et al.[15] first reported a patient with par- 8q (8q21.3→qter) and a partial monosomy 13q tial trisomy 8q in 1972. Clinical findings of partial (13q34→qter). trisomy 8q include mental retardation, growth im- Her mother was later found to carry a balanced re- pairment, dysmorphic facial features (prominent ciprocal translocation involving chromosomes 8 forehead, downslanting palpebral fissures, hyper- and 13 that could account for the chromosomal