Abstract：
BACKGROUND: Cat eye syndrome (CES) is a rare chromosomal disease, with estimated incidence of about 1 in 100,000 live newborns. The classic triad of iris coloboma, anorectal malformations, and auricular abnormalities is present in 40% of patients, and other congenital defects may also be observed. The typical associated cytogenetic anomaly relies on an extra chromosome, derived from an inverted duplication of short arm and proximal long arm of chromosome 22, resulting in partial trisomy or tetrasomy of such regions (inv dup 22pter-22q11.2).
METHODS: We report on a full-term newborn, referred to us soon after birth. Physical examination showed facial dysmorphisms, including hypertelorism, down slanted palpebral fissures, and dysplastic ears with tragus hypoplasia and pre-auricular pit. Ophthalmologic evaluation and heart ultrasound identified left chorioretinal and iris coloboma and ostium secundum type atrial septal defect, respectively. Based on the suspicion of cat eye syndrome, a standard karyotype analysis was performed, and detected an extra small marker chromosome confirming the CES diagnosis. The chromosomal abnormality was then defined by array comparative genome hybridization (a-CGH, performed also in the parents), which identified the size of the rearrangement (3 Mb), and its de novo occurrence. Postnatally, our newborn presented with persistent hypoglycemia and cholestatic jaundice. Endocrine tests revealed congenital hypothyroidism, cortisol and growth hormone (GH) deficiencies, which were treated with replacement therapies (levotiroxine and hydrocortisone). Brain magnetic resonance imaging, later performed, showed aplasia of the anterior pituitary gland, agenesis of the stalk and ectopic neurohypophysis, confirming the congenital hypopituitarism diagnosis. She was discharged at 2 months of age, and included in a multidisciplinary follow-up. She currently is 7 months old and shows a severe global growth failure, and developmental delay. She started GH replacement treatment, and continues oral hydrocortisone, along with ursodeoxycholic acid and levothyroxine, allowing an adequate control of glycemic and thyroid profiles as well as of cholestasis.
CONCLUSIONS: CES phenotypic spectrum is wide and highly variable. Our report highlights how among the possible associated endocrine disorders, congenital hypopituitarism may occur, leading to persistent hypoglycemia and cholestasis. These patients should be promptly assessed for complete hormonal evaluations, in addition to major malformations and midline anomalies. Early recognition of such defects is necessary to decrease fatal events, as well as short and long-term related adverse outcomes.
METHODS: We report on a full-term newborn, referred to us soon after birth. Physical examination showed facial dysmorphisms, including hypertelorism, down slanted palpebral fissures, and dysplastic ears with tragus hypoplasia and pre-auricular pit. Ophthalmologic evaluation and heart ultrasound identified left chorioretinal and iris coloboma and ostium secundum type atrial septal defect, respectively. Based on the suspicion of cat eye syndrome, a standard karyotype analysis was performed, and detected an extra small marker chromosome confirming the CES diagnosis. The chromosomal abnormality was then defined by array comparative genome hybridization (a-CGH, performed also in the parents), which identified the size of the rearrangement (3 Mb), and its de novo occurrence. Postnatally, our newborn presented with persistent hypoglycemia and cholestatic jaundice. Endocrine tests revealed congenital hypothyroidism, cortisol and growth hormone (GH) deficiencies, which were treated with replacement therapies (levotiroxine and hydrocortisone). Brain magnetic resonance imaging, later performed, showed aplasia of the anterior pituitary gland, agenesis of the stalk and ectopic neurohypophysis, confirming the congenital hypopituitarism diagnosis. She was discharged at 2 months of age, and included in a multidisciplinary follow-up. She currently is 7 months old and shows a severe global growth failure, and developmental delay. She started GH replacement treatment, and continues oral hydrocortisone, along with ursodeoxycholic acid and levothyroxine, allowing an adequate control of glycemic and thyroid profiles as well as of cholestasis.
CONCLUSIONS: CES phenotypic spectrum is wide and highly variable. Our report highlights how among the possible associated endocrine disorders, congenital hypopituitarism may occur, leading to persistent hypoglycemia and cholestasis. These patients should be promptly assessed for complete hormonal evaluations, in addition to major malformations and midline anomalies. Early recognition of such defects is necessary to decrease fatal events, as well as short and long-term related adverse outcomes.
摘要：
背景：猫眼综合征（CES）是一种罕见的染色体疾病，估计发病率约为100,000名活新生儿中的1名。经典的三合会虹膜缺损，肛门直肠畸形,40%的患者存在耳廓异常，和其他先天性缺陷也可以观察到。典型的相关细胞遗传学异常依赖于额外的染色体，源自22号染色体的短臂和近端长臂的反向重复，导致此类区域的部分三体性或四体性（invdup22pter-22q11.2）。
方法：我们报告了一个足月新生儿，出生后不久就提到了我们。体格检查显示面部畸形，包括超端粒,向下倾斜的睑裂，和耳屏发育不良和耳前凹陷。眼科评估和心脏超声发现左脉络膜视网膜和虹膜缺损和孔型房间隔缺损，分别。基于对猫眼综合症的怀疑,进行了标准核型分析，并检测到一个额外的小标记染色体，证实了CES的诊断。然后通过阵列比较基因组杂交（a-CGH，也在父母中表演)，确定了重排的大小(3Mb)，以及它的从头发生。出生后,我们的新生儿出现持续性低血糖和胆汁淤积性黄疸.内分泌检查显示先天性甲状腺功能减退症,皮质醇和生长激素（GH）缺乏，采用替代疗法（左旋罗素和氢化可的松）治疗。脑磁共振成像，后来表演，显示垂体前叶发育不全,茎和异位神经垂体的发育不全，确认先天性垂体功能减退症的诊断。她在2个月大的时候就出院了,并纳入多学科后续行动。她目前7个月大，显示出严重的全球增长失败，和发育迟缓。她开始了GH替代治疗,并继续口服氢化可的松，还有熊去氧胆酸和左甲状腺素,允许充分控制血糖和甲状腺特征以及胆汁淤积。
结论：CES表型谱广泛且高度可变。我们的报告强调了在可能的相关内分泌失调中，可能发生先天性垂体功能减退症,导致持续性低血糖和胆汁淤积。这些患者应及时进行全面的激素评估，除了重大畸形和中线异常.早期识别这些缺陷对于减少致命事件是必要的，以及短期和长期相关的不良结果。
方法：我们报告了一个足月新生儿，出生后不久就提到了我们。体格检查显示面部畸形，包括超端粒,向下倾斜的睑裂，和耳屏发育不良和耳前凹陷。眼科评估和心脏超声发现左脉络膜视网膜和虹膜缺损和孔型房间隔缺损，分别。基于对猫眼综合症的怀疑,进行了标准核型分析，并检测到一个额外的小标记染色体，证实了CES的诊断。然后通过阵列比较基因组杂交（a-CGH，也在父母中表演)，确定了重排的大小(3Mb)，以及它的从头发生。出生后,我们的新生儿出现持续性低血糖和胆汁淤积性黄疸.内分泌检查显示先天性甲状腺功能减退症,皮质醇和生长激素（GH）缺乏，采用替代疗法（左旋罗素和氢化可的松）治疗。脑磁共振成像，后来表演，显示垂体前叶发育不全,茎和异位神经垂体的发育不全，确认先天性垂体功能减退症的诊断。她在2个月大的时候就出院了,并纳入多学科后续行动。她目前7个月大，显示出严重的全球增长失败，和发育迟缓。她开始了GH替代治疗,并继续口服氢化可的松，还有熊去氧胆酸和左甲状腺素,允许充分控制血糖和甲状腺特征以及胆汁淤积。
结论：CES表型谱广泛且高度可变。我们的报告强调了在可能的相关内分泌失调中，可能发生先天性垂体功能减退症,导致持续性低血糖和胆汁淤积。这些患者应及时进行全面的激素评估，除了重大畸形和中线异常.早期识别这些缺陷对于减少致命事件是必要的，以及短期和长期相关的不良结果。
