PDF(Pubmed)
Abstract：
BACKGROUND: HNF1B deletion/intragenic mutations are the most commonly identified genetic cause of congenital anomalies of the kidney and urinary tract (CAKUT) suggested by fetal ultrasound findings such as: parenchymal hyperechogenicity, overt cystic changes or gross morphological urinary system (UT) abnormalities. The postnatal evolution of these 17q12 deletions encompassing the HNF1B gene-associated findings has not been assessed in depth.
METHODS: In this observational study, we present postnatal follow-up findings in 5 of 6 cases (one pregnancy was terminated on parental request) of fetal-onset cystic/hyperechogenic kidneys eventually diagnosed with 17q12 microdeletion encompassing the HNF1B gene between 2009 and 2017.
RESULTS: Complete normalization of kidney parenchymal abnormalities and of depressed neonatal renal function was observed in 4/5 and 5/5 patients within 2-4.9 years and 1.5-8 months, respectively. All 5 patients had preserved normal renal function at 3-11 years of follow-up. The evolving later-onset renal features included: hypomagnesemia, hyperuricemia, urinary tract infection (UTI), and bilateral grade 3-4 vesicoureteral reflux and bladder diverticula in 3, 3, 2, and 1 patient, respectively. HNF1B gene deletion-associated extra-renal manifestations with delayed presentation were global developmental delay/autistic spectrum disorder (ASD), rolandic-type seizures, overweight, and borderline fasting hyperglycemia observed in 1-2 patients each. Family history was positive for small-size or asymptomatic cystic kidneys with normal function, diabetes mellitus, seizures, and mental/psychiatric problems in 3/6 cases.
CONCLUSIONS: Fetal-onset HNF1B deletion-associated kidneys\' parenchymal abnormalities confirmed postnatally with initially depressed renal function might undergo complete resolution within several years and few months, respectively. However, later-onset urinary tract, metabolic, and neurodevelopmental features of this mutation might appear over years. Therefore, genetic molecular evaluation/diagnosis and continuous follow-up for evolving features are mandatory in affected children.
METHODS: In this observational study, we present postnatal follow-up findings in 5 of 6 cases (one pregnancy was terminated on parental request) of fetal-onset cystic/hyperechogenic kidneys eventually diagnosed with 17q12 microdeletion encompassing the HNF1B gene between 2009 and 2017.
RESULTS: Complete normalization of kidney parenchymal abnormalities and of depressed neonatal renal function was observed in 4/5 and 5/5 patients within 2-4.9 years and 1.5-8 months, respectively. All 5 patients had preserved normal renal function at 3-11 years of follow-up. The evolving later-onset renal features included: hypomagnesemia, hyperuricemia, urinary tract infection (UTI), and bilateral grade 3-4 vesicoureteral reflux and bladder diverticula in 3, 3, 2, and 1 patient, respectively. HNF1B gene deletion-associated extra-renal manifestations with delayed presentation were global developmental delay/autistic spectrum disorder (ASD), rolandic-type seizures, overweight, and borderline fasting hyperglycemia observed in 1-2 patients each. Family history was positive for small-size or asymptomatic cystic kidneys with normal function, diabetes mellitus, seizures, and mental/psychiatric problems in 3/6 cases.
CONCLUSIONS: Fetal-onset HNF1B deletion-associated kidneys\' parenchymal abnormalities confirmed postnatally with initially depressed renal function might undergo complete resolution within several years and few months, respectively. However, later-onset urinary tract, metabolic, and neurodevelopmental features of this mutation might appear over years. Therefore, genetic molecular evaluation/diagnosis and continuous follow-up for evolving features are mandatory in affected children.
摘要：
背景：HNF1B缺失/基因内突变是胎儿超声发现提示的肾脏和泌尿道先天性异常（CAKUT）的最常见遗传原因，例如：明显的囊性改变或大体形态泌尿系统（UT）异常。这些包含HNF1B基因相关发现的17q12缺失的出生后进化尚未得到深入评估。
方法：在这项观察性研究中，我们介绍了在2009年至2017年期间,6例(1例应父母要求终止妊娠)中的5例胎儿发病囊性/高回声肾最终诊断为包含HNF1B基因的17q12微缺失的产后随访结果.
结果：在2-4.9年和1.5-8个月内，在4/5和5/5患者中观察到肾脏实质异常和新生儿肾功能下降的完全正常化，分别。所有5例患者在3-11年随访时肾功能均保持正常。不断发展的晚期肾脏特征包括：低镁血症，高尿酸血症,尿路感染（UTI），3、3、2和1例患者的双侧3-4级膀胱输尿管反流和膀胱憩室，分别。HNF1B基因缺失相关的肾外表现与延迟表现为整体发育迟缓/自闭症谱系障碍（ASD），罗兰式癫痫发作,超重,在1-2例患者中观察到临界空腹高血糖。家族史对功能正常的小尺寸或无症状的囊性肾呈阳性，糖尿病,癫痫发作,和精神/精神问题的3/6例。
结论：出生后证实的胎儿HNF1B缺失相关肾脏实质异常，最初肾功能下降，可能在几年和几个月内完全缓解，分别。然而,晚期尿路,新陈代谢，这种突变的神经发育特征可能会出现多年。因此,在患病儿童中,必须进行遗传分子评估/诊断和对不断变化的特征进行持续随访.
方法：在这项观察性研究中，我们介绍了在2009年至2017年期间,6例(1例应父母要求终止妊娠)中的5例胎儿发病囊性/高回声肾最终诊断为包含HNF1B基因的17q12微缺失的产后随访结果.
结果：在2-4.9年和1.5-8个月内，在4/5和5/5患者中观察到肾脏实质异常和新生儿肾功能下降的完全正常化，分别。所有5例患者在3-11年随访时肾功能均保持正常。不断发展的晚期肾脏特征包括：低镁血症，高尿酸血症,尿路感染（UTI），3、3、2和1例患者的双侧3-4级膀胱输尿管反流和膀胱憩室，分别。HNF1B基因缺失相关的肾外表现与延迟表现为整体发育迟缓/自闭症谱系障碍（ASD），罗兰式癫痫发作,超重,在1-2例患者中观察到临界空腹高血糖。家族史对功能正常的小尺寸或无症状的囊性肾呈阳性，糖尿病,癫痫发作,和精神/精神问题的3/6例。
结论：出生后证实的胎儿HNF1B缺失相关肾脏实质异常，最初肾功能下降，可能在几年和几个月内完全缓解，分别。然而,晚期尿路,新陈代谢，这种突变的神经发育特征可能会出现多年。因此,在患病儿童中,必须进行遗传分子评估/诊断和对不断变化的特征进行持续随访.
