KBG syndrome (KBGS) is an autosomal dominant disorder presenting with diverse clinical features. Although multiple cases of the microdeletion subtype have been reported, discussions regarding its phenotypic characteristics remain relatively limited. This study aims to summarize the clinical features and management strategies for pediatric KBGS patients caused by 16q24.3 microdeletions, thereby enhancing awareness of this rare disease. We conducted a retrospective analysis of the clinical manifestations, genetic characteristics, and clinical management of four pediatric patients with microdeletion-type KBGS at our institution, and systematically reviewed relevant literature to compile clinical data on affected patients. All four patients exhibited typical facial features (such as cupid's bow lip, protruding ears, and thick eyebrows), skeletal abnormalities, and ocular anomalies. Whole-exome sequencing revealed a 16q24.3 microdeletion encompassing the ANKRD11 gene. A literature review identified 68 cases (including the present cases) of KBG syndrome caused by 16q24.3 microdeletions, with a male-to-female ratio of 38:21 (9 cases of unknown sex), including 6 Chinese patients. Non-Chinese patients typically exhibit distinctive facial features including a prominent nasal root (14/28, 50%) and prominent forehead (15/33, 45.45%), whereas Chinese patients display characteristic facial features such as a cupid's bow lip, protruding ears, and thick eyebrows. Among the East Asian population (represented by Chinese individuals), the incidence of prominent eyebrows, cupid's bow lip, and delayed bone age was higher than in other populations. Patients with microdeletions involving only ANKRD11 exhibited a higher prevalence of the characteristic triangular facial appearance and intellectual disability. In this study, the two children received recombinant human growth hormone therapy, achieving catch-up growth with height increases of 1.66 standard deviations and 0.68 standard deviations, respectively. The clinical phenotype of patients with microdeletion-type KBGS mainly includes characteristic facial features, macrodontia, skeletal deformities, neurological abnormalities, and eye deformities. Cupid's bow lip, protruding ears, and thick eyebrows may be characteristic facial features of Chinese children with KBGS. Genetic testing is required for definitive diagnosis. Treatment primarily relies on multidisciplinary teams providing symptomatic supportive care, with the aim of achieving early diagnosis and treatment to improve patient outcomes.

Objective: To analyze the genetic characteristics of clinical manifestations in children with KBG syndrome due to microdeletions. Methods: A retrospective case summary was conducted. Four children diagnosed with KBG syndrome due to 16q24.3 microdeletion at Children's Hospital of Zhengzhou University from July 2021 to April 2024 were enrolled.Their clinical manifestations, biochemical parameters, imaging data, whole-exome sequencing results, treatments and follow-up outcomes were reviewed. Results: The cohort included two males and two females (diagnosed at 81, 18, 26, and 56 months of age, respectively), from four unrelated families. All patients exhibited peculiar facial features (Cupid's bowed-shaped lips, prominent ears, thick eyebrows), skeletal abnormalities (brachydactyly, abnormal ribs, short stature, etc.), ocular anomalies (astigmatism, strabismus, amblyopia, etc.), intrauterine growth restriction, and developmental retardation. Case 2, 3, 4 had cranial imaging abnormalities, including thin anterior pituitary lobes with pineal cyst, left ventricular cyst, and abnormal pituitary stalk or lateral ventricles with sinusitis, respectively. Two children had intellectual disability, two had congenital heart disease, and one had delayed bone age and hair abnormalities. Whole exome genomic sequencing confirmed 16q24.3 microdeletions encompassing ANKRD11 gene in all four cases. Two children treated with recombinant human growth hormone achieved height increments of 1.5 s and 0.4 s, respectively. Conclusions: Typical features of 16q24.3 microdeletion-induced KBG syndrome include peculiar facial features, macrodontia, skeletal anomalies, neurological abnormalities, and ocular defects. Genetic testing is essential for definitive diagnosis. The treatment of KBG syndrome requires early diagnosis and multidisciplinary collaboration to implement individualized treatment for multisystem symptoms. 目的： 分析微缺失导致的KBG综合征患儿的临床表现和遗传学特征。 方法： 回顾性病例总结。以2021年7月至2024年4月郑州大学附属儿童医院收治的4例16q24.3微缺失导致的KBG综合征患儿为研究对象，对其临床表现、生化指标、影像学资料、全外显子组测序结果、治疗及随访情况等进行归纳总结。 结果： 4例患儿中男2例、女2例，诊断年龄分别为81、18、26、56月龄，来自4个家系，均有特殊面容（丘比特弓形唇、耳廓突出、浓眉）、骨骼异常（短指、异常肋骨、身材矮小等）、眼部异常（散光、斜视、弱视等）、宫内发育异常、生长发育迟缓的临床表型。例2、3、4患儿头颅影像学分别表现为垂体前叶薄、松果体囊肿；左侧脑室囊肿；垂体柄、侧脑室有异常且伴鼻窦炎。2例患儿存在智力残疾，2例患儿存在先天性心脏病，1例患儿存在骨龄延迟和毛发异常。4例患儿的全外显子组测序均检出包含ANKRD11基因的16q24.3微缺失。2例矮小患儿使用重组人生长激素治疗后，身高分别增加了1.5 s、0.4 s。 结论： 特殊面容、巨牙畸形、骨骼异常、神经系统异常、眼部异常等是16q24.3微缺失导致的KBG综合征的常见表型；丘比特弓形唇、耳廓突出、浓眉是微缺失型KBG综合征患儿的特殊面容表现；确诊需依据基因检测。KBG综合征的治疗需实现早期诊断，通过多学科协作，针对多系统症状实施个体化治疗。.

KBG syndrome is characterized by intellectual disability, and craniofacial and skeletal abnormalities. We report the case of a 5-year-old boy with KBG syndrome with 16q24.3 microdeletion who showed complex strabismus. Left esotropia and ptosis was first noticed by parents at 18 months of age. He also showed submucosal cleft palate, velopharyngeal insufficiency, prominent eyebrows, short fifth fingers, and fetal finger pad. Marginal reflex distances were +4 mm in the right eye and +1.5 mm in the left eye. He had 18Δ of left esotropia, and 12Δ of left hypotropia, which increased with head tilt to the right. Ductions and versions showed bilateral upgaze limitation, more on the right eye, and mild limitation of downgaze on adduction in both eyes. Anti-acetylcholine receptor antibody test, ice test, thyroid function test and the repetitive nerve stimulation test were all negative. Magnetic resonance imaging revealed normal orbital structures, including the bony orbit, oculomotor, trochlear, and abducens nerves, and extraocular muscles in both eyes.

Background: KBG syndrome is a multisystem developmental disorder characterized by macrodontia of the upper permanent incisors, distinctive facial features, a short stature, developmental delay, variable intellectual disability, and behavioral issues. Heterozygous chromosomal deletion encompassing the partial or entire ANKRD11 gene, as well as the loss of function mutations, result in haploinsufficiency of the gene, leading to KBG syndrome. This indicates that precise levels of ANKRD11 transcripts or protein are essential for human development. Clinical report: Here, we report three individuals who present with clinical features of KBG syndrome. These individuals carry microdeletions encompassing only the non-coding exon 1 of ANKRD11 and its upstream region. Our molecular analysis showed that this deletion leads to reduction in the ANKRD11 transcript and global transcriptome alterations similar to those seen in KBG syndrome patients. Conclusions: We concluded that microdeletions involving non-coding exon 1 of ANKRD11 lead to KBG syndrome. Our study suggests the utility of transcriptome analysis in aiding the interpretation of novel copy number variants in the non-coding genomic region of ANKRD11.

To investigate the association of agenesis of the ductus venosus (ADV) with genetic abnormalities using genetic studies-Chromosomal Microarray Analysis (CMA) and Exome Sequencing (ES). Retrospective study of all fetuses diagnosed with ADV between January 2013 and December 2022 in a tertiary center. ADV was diagnosed in 33 fetuses. The diagnosis was made at a mean gestational age of 21.2 ± 8.4 weeks. Conventional karyotype was applied in a single fetus (3.0%), CMA was applied in 21 fetuses (66.7%), and five fetuses (22.8%) were additionally tested with ES. ADV was isolated in eight fetuses (24%), whereas in 25 (76%) it was associated with abnormal ultrasound findings, including increased nuchal translucency (NT), intrauterine growth restriction (IUGR) and variable structural malformations, mostly cardiac (42%) followed by central nervous system (CNS) and skeletal malformations (24%). Genetic abnormalities were found in six fetuses out of 22 investigated (27%), of which 3 were detected by ES, 3 by CMA and 1 by conventional karyotype. A higher incidence of genetic aberrations was evident among ADVs associated with abnormal ultrasound findings. Genetic abnormalities were indicative of Prader Willi/Angelman syndrome, Noonan syndrome, CASK related disorder, 16q24.3 microdeletion syndrome and Trisomy 21. ADV associated with abnormal ultrasound findings is commonly correlated with genetic abnormalities and consequently unfavorable pregnancy outcomes. Our study emphasizes the value of genetic studies chiefly among cases associated with abnormal ultrasound findings, enabling early diagnosis of fetal pathologies associated with ADV, and providing better parental counseling.