Abstract：
BACKGROUND: Chromosome 13q deletion syndrome shows variable clinical features related to the different potential breakpoints in chromosome 13q. The severely malformed phenotype is known to be associated with the deletion of a critical region in 13q32. However, esophageal atresia is a rare symptom and the relevant region is unknown. Thus, determining the association between accurate breakpoints and new clinical features is essential.
METHODS: A 28-year-old Japanese primigravid woman was referred for fetal growth restriction, absence of a gastric bubble, cerebellar hypoplasia, overlapping fingers, and polyhydramnios at 31 weeks gestation. At 38 + 0 weeks, she delivered a 1774 g female infant. The infant presented with isolated esophageal atresia (Gross type A), Dandy-Walker malformation, right microphthalmia, left coloboma, overlapping fingers, pleurocentrum in the thoracic vertebrae, reduced anogenital distance, and hearing loss. Her karyotype was diagnosed as 46,XX,del(13)(q32.1-qter) by amniocentesis, but array comparative genomic hybridization after birth revealed the deletion of 13q31.3-qter. At 48 days after birth, the infant underwent surgery for esophageal atresia and was later discharged from the hospital at 7 months of age.
CONCLUSIONS: This case report and the literature reviews supports the previous findings on the pathological roles of haploinsufficiency of the ZIC2/ZIC5 in Dandy-Walker malformation and the EFBN2 haploinsufficiency in eye malformation and hearing loss. Furthermore, the possible involvement of IRS2, COLA1, and COLA2 in eye malformation were identified. This is the first case of 13q deletion syndrome with esophageal atresia (Gross A), but it may be a symptom of VATER/VACTER association (vertebral defects, anorectal malformations, cardiac defects, tracheoesophageal fistula with or without esophageal atresia, renal malformations, and limb defects), as in the previous cases. These symptoms might also be associated with EFBN2 haploinsufficiency, although further research is required.
METHODS: A 28-year-old Japanese primigravid woman was referred for fetal growth restriction, absence of a gastric bubble, cerebellar hypoplasia, overlapping fingers, and polyhydramnios at 31 weeks gestation. At 38 + 0 weeks, she delivered a 1774 g female infant. The infant presented with isolated esophageal atresia (Gross type A), Dandy-Walker malformation, right microphthalmia, left coloboma, overlapping fingers, pleurocentrum in the thoracic vertebrae, reduced anogenital distance, and hearing loss. Her karyotype was diagnosed as 46,XX,del(13)(q32.1-qter) by amniocentesis, but array comparative genomic hybridization after birth revealed the deletion of 13q31.3-qter. At 48 days after birth, the infant underwent surgery for esophageal atresia and was later discharged from the hospital at 7 months of age.
CONCLUSIONS: This case report and the literature reviews supports the previous findings on the pathological roles of haploinsufficiency of the ZIC2/ZIC5 in Dandy-Walker malformation and the EFBN2 haploinsufficiency in eye malformation and hearing loss. Furthermore, the possible involvement of IRS2, COLA1, and COLA2 in eye malformation were identified. This is the first case of 13q deletion syndrome with esophageal atresia (Gross A), but it may be a symptom of VATER/VACTER association (vertebral defects, anorectal malformations, cardiac defects, tracheoesophageal fistula with or without esophageal atresia, renal malformations, and limb defects), as in the previous cases. These symptoms might also be associated with EFBN2 haploinsufficiency, although further research is required.
摘要：
背景：染色体13q缺失综合征显示出与染色体13q中不同的潜在断点相关的可变临床特征。已知严重畸形的表型与13q32中关键区域的缺失有关。然而,食管闭锁是一种罕见的症状，相关区域未知。因此，确定准确的断点与新的临床特征之间的关联至关重要.
方法：一名28岁的日本初产妇因胎儿生长受限而转诊，没有胃泡，小脑发育不全,重叠的手指，妊娠31周时羊水过多。在38+0周，她接生了一名1774克女婴。婴儿出现孤立性食管闭锁（GrossA型），Dandy-Walker畸形,右小眼症,左结肠瘤,重叠的手指，胸椎的胸膜中枢,肛门生殖器距离缩短,和听力损失。她的核型被诊断为46，XX，del（13）（q32.1-qter）通过羊膜穿刺术，但是出生后的阵列比较基因组杂交显示13q31.3-qter缺失。出生后48天，该婴儿因食道闭锁接受手术治疗,7个月时出院.
结论：本病例报告和文献综述支持先前关于ZIC2/ZIC5单倍体功能不全在Dandy-Walker畸形和EFBN2单倍体功能不全在眼畸形和听力损失中的病理作用的发现。此外，发现IRS2,COLA1和COLA2可能参与眼畸形.这是首例13q缺失综合征伴食管闭锁（GrossA），但这可能是VATER/VACTER关联的症状（椎骨缺损，肛门直肠畸形,心脏缺陷,伴或不伴食管闭锁的气管食管瘘，肾畸形,和肢体缺陷)，就像以前的情况一样。这些症状也可能与EFBN2单倍体功能不全有关，虽然需要进一步的研究。
方法：一名28岁的日本初产妇因胎儿生长受限而转诊，没有胃泡，小脑发育不全,重叠的手指，妊娠31周时羊水过多。在38+0周，她接生了一名1774克女婴。婴儿出现孤立性食管闭锁（GrossA型），Dandy-Walker畸形,右小眼症,左结肠瘤,重叠的手指，胸椎的胸膜中枢,肛门生殖器距离缩短,和听力损失。她的核型被诊断为46，XX，del（13）（q32.1-qter）通过羊膜穿刺术，但是出生后的阵列比较基因组杂交显示13q31.3-qter缺失。出生后48天，该婴儿因食道闭锁接受手术治疗,7个月时出院.
结论：本病例报告和文献综述支持先前关于ZIC2/ZIC5单倍体功能不全在Dandy-Walker畸形和EFBN2单倍体功能不全在眼畸形和听力损失中的病理作用的发现。此外，发现IRS2,COLA1和COLA2可能参与眼畸形.这是首例13q缺失综合征伴食管闭锁（GrossA），但这可能是VATER/VACTER关联的症状（椎骨缺损，肛门直肠畸形,心脏缺陷,伴或不伴食管闭锁的气管食管瘘，肾畸形,和肢体缺陷)，就像以前的情况一样。这些症状也可能与EFBN2单倍体功能不全有关，虽然需要进一步的研究。
