Scholarlink

<p>Lennox-Gastaut syndrome (LGS) represents a severe developmental and epileptic encephalopathy(DEE) with heterogeneous etiologies. Despite advances in genomic medicine, a substantial proportion of patients remain without molecular diagnosis. RNU2-2, encoding a core spliceosome component, has recently emerged as a cause of severe neurodevelopmental disorders through both dominant and recessive inheritance patterns. We report a 14-year-old male with a decade-long undiagnosed DEE characterized by developmental delays from 6 months, multiple seizure types beginning at 15 months, progressive dystonia, spasticity, and microcephaly. Initial investigations suggested Glucose Transporter 1 (GLUT1) deficiency based on low cerebrospinal fluid glucose and diffuse cerebral hypometabolism on positron emission tomography, but <i>SLC2A1</i> sequencing was negative and therapeutic trials with ketogenic diet and triheptanoin proved ineffective. His seizures evolved to fulfill LGS diagnostic criteria with electroencephalography demonstrating generalized slow spike-waves and generalized paroxysmal fast activity. Despite multiple genetic evaluations including microarray and whole genome sequencing, no diagnosis was established until enrollment in the Undiagnosed Diseases Network revealed compound heterozygous RNU2-2 variants: n.100T &gt; G (maternal) and n.116_127del (paternal). This case represents one of the first reports of autosomal recessive RNU2-2-related neurodevelopmental disorder presenting as LGS. It illustrates the diagnostic challenge of metabolic phenocopies and highlights the critical importance of analyzing non-coding RNA genes in undiagnosed DEEs. Recognition of RNU2-2-related disorders expands the genetic landscape of LGS and emphasizes the value of systematic genomic reanalysis in patients without molecular diagnosis despite conventional testing.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Biallelic RNU2-2–related neurodevelopmental disorder presenting as Lennox-Gastaut syndrome

  • 期刊论文

  • 发表日期：

    2026年3月12日

查看全文
  • Debopam Samanta

摘要

Lennox-Gastaut syndrome (LGS) represents a severe developmental and epileptic encephalopathy(DEE) with heterogeneous etiologies. Despite advances in genomic medicine, a substantial proportion of patients remain without molecular diagnosis. RNU2-2, encoding a core spliceosome component, has recently emerged as a cause of severe neurodevelopmental disorders through both dominant and recessive inheritance patterns. We report a 14-year-old male with a decade-long undiagnosed DEE characterized by developmental delays from 6 months, multiple seizure types beginning at 15 months, progressive dystonia, spasticity, and microcephaly. Initial investigations suggested Glucose Transporter 1 (GLUT1) deficiency based on low cerebrospinal fluid glucose and diffuse cerebral hypometabolism on positron emission tomography, but SLC2A1 sequencing was negative and therapeutic trials with ketogenic diet and triheptanoin proved ineffective. His seizures evolved to fulfill LGS diagnostic criteria with electroencephalography demonstrating generalized slow spike-waves and generalized paroxysmal fast activity. Despite multiple genetic evaluations including microarray and whole genome sequencing, no diagnosis was established until enrollment in the Undiagnosed Diseases Network revealed compound heterozygous RNU2-2 variants: n.100T > G (maternal) and n.116_127del (paternal). This case represents one of the first reports of autosomal recessive RNU2-2-related neurodevelopmental disorder presenting as LGS. It illustrates the diagnostic challenge of metabolic phenocopies and highlights the critical importance of analyzing non-coding RNA genes in undiagnosed DEEs. Recognition of RNU2-2-related disorders expands the genetic landscape of LGS and emphasizes the value of systematic genomic reanalysis in patients without molecular diagnosis despite conventional testing.