摘要对2024年5月南通大学附属常州儿童医院消化营养科收治的1例基因诊断明确的Kleefstra综合征2型(KLEFS2)患儿的临床资料进行回顾性分析。患儿，男，2岁6个月，出生后大运动里程碑发育迟缓，语言发育迟缓，喂养困难，合并左侧隐睾、房间隔缺损，2岁6月龄不会喊"爸爸/妈妈"，呼名反应差，饮食仍以半流质、流质为主。查体：体重11 kg(－1.64 SD)，身高82 cm(－2.94 SD)，体型偏瘦，身材矮小，浓眉，低鼻梁，后背毛发较旺盛，双手掌纹为贯通掌。全外显子组基因测序发现患儿存在组蛋白赖氨酸N-甲基转移酶2C( KMT2C)基因c.5742(exon36)_5743(exon36)dup/p.(S1915Ffs*25)(NM_170606)杂合变异。根据美国医学遗传学与基因组学学会变异评级指南，该变异评级为可能致病变异。结合患儿临床特征和分子遗传学检测结果，诊断为KLEFS2。经Sanger测序验证患儿父亲为野生型，母亲携带该变异，但母亲仅表现为体格发育迟缓、身材矮小。KLEFS2是一种罕见的常染色体显性遗传病，其基因变异和临床表型存在高度异质性，目前全球已报道19例KLEFS2；本研究中所报道的患儿通贯掌、多毛为该疾病谱未报道过的临床表现，所鉴定到的变异尚未见文献报道。本研究丰富了 KMT2C基因的变异谱，并为KLEFS2的疾病表型谱扩充提供了新的临床证据。

abstractsThe clinical data of a pediatric patient with Kleefstra syndrome 2 (KLEFS2) diagnosed at the Department of Gastroenterology and Nutrition, Changzhou Children′s Hospital Affiliated to Nantong University in May 2024 were retrospectively analyzed.The patient was a 2-year-and-6-month-old male who had delayed language-motor development, feeding difficulties, left cryptorchidism, and atrial septal defect.He could not say " papa/mama" at the age of 2 years and 6 months, with poor response to his name, and mainly consumed semi-liquid and liquid foods.Physical examination showed his weight was 11 kg (-1.64 SD) and his height was 82 cm (-2.94 SD).He had thick eyebrows, low nasal bridge, abundant hair on the back and the simian line on the palms of both hands.Whole exome sequencing revealed that the patient had a heterozygous variant in the histone-lysine N-methyltransferase 2C ( KMT2C) gene [c.5742(exon36)_5743(exon36)dup/p.(S1915Ffs*25)(NM_170606)].It could be the pathogenic variation according to the American College of Medical Genetics and Genomics variant interpretation guidelines.Based on the patient′s clinical characteristics and molecular genetic testing results, KLEFS2 was diagnosed.Sanger sequencing showed that the patient′s father has a wild-type KMT2C gene, and his mother carries this mutation in the KMT2C gene, but she only exhibits delayed physical development and short stature.KLEFS2 is a rare autosomal dominant genetic disease, and there is heterogeneity in its genetic variation and clinical phenotype.A total of 19 cases of KLEFS2 have been reported globally.This article reports new clinical manifestations of KLEFS2, including simian line and excessive hair growth.c.5742(exon36)_5743(exon36)dup is a newly found KMT2C mutation that enriches the KMT2C variation spectrum and expands the phenotypic spectrum of KLEFS2.