Meyer Alayne P, Koboldt Daniel C, Ramadesikan Swetha, Zajo Kristin, Hernandez Gonzalez Maria E, Miller Anthony R, Depoorter Douglas, Comer Catherine P, Geller James I, Somers Katherine, Shah Nilay, Leung Marco L
Division of Genetic and Genomic Medicine, Nationwide Children's Hospital, Columbus, Ohio, USA.
Center for Gene Therapy, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, Ohio, USA.
Mol Genet Genomic Med. 2025 Jul;13(7):e70124. doi: 10.1002/mgg3.70124.
Perlman syndrome is a rare autosomal recessive overgrowth disorder with a predisposition to Wilms tumor, caused by biallelic variants in DIS3L2. The majority of patients die in infancy due to respiratory and/or renal failure, limiting the reports of patients surviving into childhood.
Exome sequencing was performed in the proband and her older brother. A younger sibling subsequently underwent targeted variant analysis. RNA sequencing was utilized to investigate the functional impact of the missense variant.
Three siblings presented at birth with fetal macrosomia, dysmorphic facial features, and facial hypotonia. The proband had early speech delay and was diagnosed with Wilms tumor at 3 years old. Her brothers both had developmental delay presenting within the first year of life. Genetic testing identified compound heterozygous variants in DIS3L2 (NM_152383.5): c.127C>T (p.Arg43Ter) (paternal)/c.2381G>A (p.Arg794His) (maternal).
Our findings expand the genetic and clinical spectrums associated with Perlman syndrome and increase the understanding of the phenotype observed in childhood. They also support consideration of genetic testing for Perlman syndrome in individuals and sibships with macrosomia, developmental delay, and characteristic facial dysmorphisms, with or without the presence of Wilms tumor.
佩尔曼综合征是一种罕见的常染色体隐性过度生长疾病，易患威尔姆斯瘤，由DIS3L2基因的双等位基因变异引起。大多数患者因呼吸和/或肾衰竭在婴儿期死亡，这限制了存活至儿童期患者的报道。
对先证者及其哥哥进行外显子组测序。随后对一名弟弟进行了靶向变异分析。利用RNA测序研究错义变异的功能影响。
三名同胞出生时均表现为巨大胎儿、面部畸形特征和面部肌张力减退。先证者有早期语言发育迟缓，3岁时被诊断为威尔姆斯瘤。她的两个哥哥在生命的第一年内均出现发育迟缓。基因检测在DIS3L2基因（NM_152383.5）中鉴定出复合杂合变异：c.127C>T（p.Arg43Ter）（父源）/c.2381G>A（p.Arg794His）（母源）。
我们的研究结果扩展了与佩尔曼综合征相关的遗传和临床谱，增进了对儿童期观察到的表型的理解。它们还支持对有巨大胎儿、发育迟缓及特征性面部畸形的个体和同胞进行佩尔曼综合征基因检测，无论是否存在威尔姆斯瘤。
