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Abstract：
KBG syndrome is a rare genetic disorder involving macrodontia of the upper central incisors, craniofacial, skeletal, and neurologic symptoms, caused either by a heterozygous variant in ANKRD11 or deletion of 16q24.3, including ANKRD11. Diagnostic criteria were proposed in 2007 based on 50 cases, but KBG syndrome remains underdiagnosed.
Whole exome sequencing (WES) and array comparative genomic hybridization (array CGH) were conducted for genetic analysis and patient phenotypes were characterized based on medical records.
Eight patients from seven unrelated families were confirmed with KBG syndrome. All patients (8/8, 100%) had some degree of craniofacial dysmorphism and developmental delay or intellectual disabilities. Triangular face, synophrys, anteverted nostril, prominent ears, long philtrum, and tented upper lip, which are typical facial dysmorphism findings in patients with KBG syndrome, were uniformly identified in the eight patients participating in this study, with co-occurrence rates of 4/8 (50%), 4/8 (50%), 4/8 (50%), 4/8 (50%), 5/8 (62.5%), and 5/8 (62.5%), respectively. Various clinical manifestations not included in the diagnostic criteria were observed. Six patients had point mutations in ANKRD11, one had an exonic deletion of ANKRD11, and one had a 16q24.3 microdeletion. According to the ACMG guidelines, all mutations were classified as pathogenic. The c.2454dup (p.Asn819fs*1) mutation in Pt 4 was reported previously. The remaining variants (c.397 + 1G>A, c.226 + 1G>A, c.2647del (p.Glu883Argfs*94), and c.4093C>T (p.Arg1365Ter)) were novel.
The clinical and molecular features of eight patients from seven unrelated Korean families with KBG syndrome described here will assist physicians in understanding this rare genetic condition.
Whole exome sequencing (WES) and array comparative genomic hybridization (array CGH) were conducted for genetic analysis and patient phenotypes were characterized based on medical records.
Eight patients from seven unrelated families were confirmed with KBG syndrome. All patients (8/8, 100%) had some degree of craniofacial dysmorphism and developmental delay or intellectual disabilities. Triangular face, synophrys, anteverted nostril, prominent ears, long philtrum, and tented upper lip, which are typical facial dysmorphism findings in patients with KBG syndrome, were uniformly identified in the eight patients participating in this study, with co-occurrence rates of 4/8 (50%), 4/8 (50%), 4/8 (50%), 4/8 (50%), 5/8 (62.5%), and 5/8 (62.5%), respectively. Various clinical manifestations not included in the diagnostic criteria were observed. Six patients had point mutations in ANKRD11, one had an exonic deletion of ANKRD11, and one had a 16q24.3 microdeletion. According to the ACMG guidelines, all mutations were classified as pathogenic. The c.2454dup (p.Asn819fs*1) mutation in Pt 4 was reported previously. The remaining variants (c.397 + 1G>A, c.226 + 1G>A, c.2647del (p.Glu883Argfs*94), and c.4093C>T (p.Arg1365Ter)) were novel.
The clinical and molecular features of eight patients from seven unrelated Korean families with KBG syndrome described here will assist physicians in understanding this rare genetic condition.
摘要：
背景：KBG综合征是一种罕见的遗传性疾病，涉及上中央切牙的巨大牙体，颅面,骨骼，和神经症状，由ANKRD11中的杂合变体或16q24.3缺失引起，包括ANKRD11。2007年根据50例病例提出诊断标准，但KBG综合征仍未被诊断.
方法：进行全外显子组测序（WES）和阵列比较基因组杂交（阵列CGH）进行遗传分析，并根据病历对患者表型进行表征。
结果：来自7个无关家庭的8例患者被证实患有KBG综合征。所有患者（8/8，100％）均有一定程度的颅面畸形，发育迟缓或智力障碍。三角面,synphrys,前鼻孔，突出的耳朵,longphiltrum,上唇隆起，这是KBG综合征患者典型的面部畸形表现，在参与这项研究的八名患者中被统一识别，共现率为4/8(50%)，4/8（50%），4/8（50%），4/8（50%），5/8（62.5%），和5/8（62.5%），分别。观察到诊断标准中未包括的各种临床表现。6例患者在ANKRD11中有点突变，1例具有ANKRD11的外显子缺失，1例具有16q24.3微缺失。根据ACMG指南,所有突变均被分类为致病性.c.2454dup（p。先前报道了Pt4中的Asn819fs*1）突变。其余的变体（c.397+1G>A，c.226+1G>A，c.2647del（p.Glu883Argfs*94),和c.4093C>T（p。Arg1365Ter））是新颖的。
结论：本文描述的来自7个无关韩国KBG综合征家庭的8名患者的临床和分子特征将有助于医生了解这种罕见的遗传状况。
方法：进行全外显子组测序（WES）和阵列比较基因组杂交（阵列CGH）进行遗传分析，并根据病历对患者表型进行表征。
结果：来自7个无关家庭的8例患者被证实患有KBG综合征。所有患者（8/8，100％）均有一定程度的颅面畸形，发育迟缓或智力障碍。三角面,synphrys,前鼻孔，突出的耳朵,longphiltrum,上唇隆起，这是KBG综合征患者典型的面部畸形表现，在参与这项研究的八名患者中被统一识别，共现率为4/8(50%)，4/8（50%），4/8（50%），4/8（50%），5/8（62.5%），和5/8（62.5%），分别。观察到诊断标准中未包括的各种临床表现。6例患者在ANKRD11中有点突变，1例具有ANKRD11的外显子缺失，1例具有16q24.3微缺失。根据ACMG指南,所有突变均被分类为致病性.c.2454dup（p。先前报道了Pt4中的Asn819fs*1）突变。其余的变体（c.397+1G>A，c.226+1G>A，c.2647del（p.Glu883Argfs*94),和c.4093C>T（p。Arg1365Ter））是新颖的。
结论：本文描述的来自7个无关韩国KBG综合征家庭的8名患者的临床和分子特征将有助于医生了解这种罕见的遗传状况。
