DataSheet2_Case Report: An Infant With Kabuki Syndrome, Alobar Holoprosencephaly and Truncus Arteriosus: A Case for Whole Exome Sequencing in Neonates With Congenital Anomalies.PDF

Kabuki syndrome is a rare multiple anomalies syndrome associated with mutations in KMT2D or KDM6A. It is characterized by infantile hypotonia, developmental delay and/or intellectual disability, long palpebral fissures with everted lateral third of the lower eyelids and typical facial features. Intracranial anomalies occur infrequently in patients with KS and holoprosencephaly has only been recently described. Additionally, though congenital heart diseases are common in patients with KS, to our knowledge truncus arteriosus has never been reported in a patient with KS. We present an unusual case of KS in an infant with holoprosencephaly and truncus arteriosus with partial anomalous pulmonary venous return. Duo whole exome sequencing in our patient identified a pathogenic nonsense variant in exon 10 of KMT2D (c.2782C > T; p. Gln928*) establishing the diagnosis. This report further expands the phenotypic spectrum of patients with Kabuki syndrome and emphasizes the utility of performing large scale sequencing in neonates with multiple congenital anomalies.

歌舞伎综合征（Kabuki syndrome）是一种罕见的多发畸形综合征，与KMT2D或KDM6A基因突变相关。该病以婴儿期肌张力低下、发育迟缓及/或智力障碍、长睑裂伴下眼睑外侧三分之一外翻，以及典型面容为特征。颅内畸形在歌舞伎综合征患者中少见，而前脑无裂畸形的相关报道直至近年才出现。此外，尽管先天性心脏病在歌舞伎综合征患者中较为常见，但据我们所知，尚未有永存动脉干合并歌舞伎综合征的病例报道。本文报告1例罕见的歌舞伎综合征患儿，同时合并前脑无裂畸形及永存动脉干伴部分性肺静脉异位引流。对该患者行双人全外显子组测序，检出KMT2D基因第10外显子存在致病性无义变异（c.2782C>T；p.Gln928*），从而明确诊断。本报告进一步拓展了歌舞伎综合征的表型谱，并强调了对多发先天性畸形新生儿开展大规模测序的临床价值。