Dantam Christina R, Wilkes Elizabeth, Summers Holly N, Morris Colleen A, Ahad Rooman F
Kirk Kerkorian School of Medicine, University of Nevada, Las Vegas, Las Vegas, NV.
Grant a Gift Autism Foundation - Ackerman Center in alliance with UNLV Kirk Kerkorian School of Medicine, Las Vegas, NV.
Medicine (Baltimore). 2025 Aug 1;104(31):e43631. doi: 10.1097/MD.0000000000043631.
KBG syndrome is a rare, autosomal dominant neurodevelopmental disorder characterized by developmental delay, macrodontia, distinctive facial features, and a range of systemic manifestations.
We report a pediatric patient with a history of global developmental delay, autism spectrum disorder, sensorineural hearing loss, and spastic diplegia who developed episodic, unilateral dystonic spells beginning at age 7, leading to impaired mobility.
Initial genetic testing revealed a maternally inherited 3p26 duplication, which did not fully account for the patient's clinical presentation. Whole exome sequencing (WES) was subsequently performed and identified a pathogenic frameshift mutation in ANKRD11, confirming a diagnosis of KBG syndrome. Additional genetic variants were found in CDH23, potentially explaining the patient's profound hearing loss.
After receiving a diagnosis, the patient received multidisciplinary care including intensive speech, occupational, physical, applied behavior analysis therapies, and educational planning to address his neurodevelopmental needs.
WES established a unifying diagnosis that better accounted for the patient's constellation of findings. Recognition of KBG syndrome facilitated appropriate medical, rehabilitative, and educational interventions. The presence of paroxysmal dystonia, previously unrecognized in KBG syndrome, adds to the expanding phenotypic spectrum.
This case underscores the diagnostic value of WES in patients with complex neurodevelopmental presentations and unexplained movement disorders. Our findings support the inclusion of ANKRD11 in the differential for pediatric dystonia and suggest a potential, previously underrecognized neurologic feature of KBG syndrome. Broader access to genomic diagnostics may reduce the diagnostic odyssey for similar patients and inform more targeted care strategies.
KBG综合征是一种罕见的常染色体显性神经发育障碍，其特征为发育迟缓、巨牙症、独特的面部特征以及一系列全身表现。
我们报告了一名患有全面发育迟缓、自闭症谱系障碍、感音神经性听力损失和痉挛性双侧瘫的儿科患者，该患者在7岁时开始出现发作性、单侧肌张力障碍发作，导致行动能力受损。
最初的基因检测显示为母系遗传的3p26重复，这并不能完全解释患者的临床表现。随后进行了全外显子组测序（WES），并在ANKRD11中鉴定出一个致病性移码突变，从而确诊为KBG综合征。在CDH23中发现了其他基因变异，可能解释了患者严重的听力损失。
确诊后，患者接受了多学科护理，包括强化言语、职业、物理、应用行为分析治疗以及教育规划，以满足他的神经发育需求。
WES建立了一个统一的诊断，能更好地解释患者的一系列检查结果。认识到KBG综合征有助于进行适当的医疗、康复和教育干预。阵发性肌张力障碍的存在，此前在KBG综合征中未被认识到，这增加了不断扩大的表型谱。
该病例强调了WES在患有复杂神经发育表现和不明原因运动障碍患者中的诊断价值。我们的研究结果支持将ANKRD11纳入小儿肌张力障碍的鉴别诊断，并提示KBG综合征存在一种潜在的、此前未被充分认识的神经学特征。更广泛地使用基因组诊断可能会减少类似患者的诊断历程，并为更有针对性的护理策略提供依据。
