Identification of a novel homozygous FRRS1L variant in a Chinese girl with development delay and epilepsy: a case report

Background Pathogenic variants in the FRRS1L gene are associated with developmental and epileptic encephalopathy 37 (DEE37, OMIM: 616981). Patients carrying FRRS1L variants typically exhibit global developmental delay, epileptic encephalopathy, hyperkinetic movement disorder with choreoathetosis, spasticity, and rigidity. However, rare variants have been reported. Case presentation Here, we report a girl presenting with epilepsy, global developmental delay, choreiform movement disorder, and unique thyroid dysfunction and elevated levels of blood ammonia and lactic acid. Although therapeutic intervention with adrenocorticotropic hormone (ACTH), valproic acid, and oral prednisone successfully achieved seizure control and electroencephalographic (EEG) improvement, the patient passed away from an unclear cause. Whole exome sequencing (WES) revealed a novel homozygous FRRS1L variant (NM_014334.4: exon5: c.725 A > G(p.His242Arg), OMIM: 604574). Sanger sequencing confirmed that the variant was inherited from her parents. Furthermore, we summarized previously reported variants and compared the phenotypes among affected patients. Conclusion To our knowledge, this is the first reported Chinese case carrying FRRS1L variants. Our study expands the genetic and phenotypic spectrums of DEE37, provides novel evidence supporting the correlation between FRRS1L variants and DEE37, and underscores the necessity for dynamic EEG monitoring and proactive management in high-risk patients with refractory seizures.