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. 2024 Mar 8;6(1):6.
doi: 10.1186/s42494-024-00149-4.

Genetic variant reanalysis reveals a case of Sandhoff disease with onset of infantile epileptic spasm syndrome

Qi Zhang  1   2 , Liping Zou  2 , Qian Lu  1   2 , Qiuhong Wang  1   2 , Shuo Dun  1   2 , Jing Wang  3
Affiliations

Genetic variant reanalysis reveals a case of Sandhoff disease with onset of infantile epileptic spasm syndrome

Qi Zhang et al. Acta Epileptol. .

Abstract

Background: Sandhoff disease (SD) i s an autosomal recessive lysosomal disease with clinical manifestations such as epilepsy, psychomotor retardation and developmental delay. However, infantile SD with onset of infantile epilepsy spasm syndrome (IESS) is extremely rare.

Case presentation: The case presented here was a 22-month-old boy, who presented with IESS and psychomotor retardation/regression at 6 months of age. The patient showed progressive aggravation of seizures and excessive startle responses. The whole exome sequencing data, which initially revealed negative results, were reanalyzed and indicated a homozygous mutation at the c.1613 + 4del splice site of the HEXB gene. The activities of β-hexosaminidase A and total hexosaminidase were significantly decreased. The fundus examination showed cherry red spots at the macula.

Conclusions: IESS can be an epileptic phenotype of infantile SD. Clinical phenotypes should be adequately collected in genetic testing. In the case of negative sequencing results, gene variant reanalysis can be performed when the patients show clinically suspicious indications.

Keywords: HEXB gene; Cherry red spot; Gene variant reanalysis; Human phenotype ontology; Infantile Sandhoff disease; Infantile epilepsy spasm syndrome.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The studies involving human participants were reviewed and approved by the the Institutional Review Board of Chinese PLA General Hospital(The ethics number: 2023–143). Written informed consent to participate in this study was provided by the participants’ legal guardian. Competing interests: Author Liping Zou is the member of the Editorial Board for Acta Epileptologica, who was not involved in the journal’s review of, or decisions related to this manuscript.

Figures

Fig. 1
Fig. 1
EEG recordings of the case. a The background EEG at the age of 16 months. b EEG recordings at the attack period of at the age of 16 months. c The background EEG at the age of 22 months. d The EEG recordings during a tonic seizure at the age of 22 months. e Atypical high arrhythmia during sleep at the age of 22 months. f The EEG recordings during a sound-evoked startle response in the child, manifested as eye squeezing, nervousness, and shoulder lifting
Fig. 2
Fig. 2
Cranial MRI of the case at age 22 months. a, b T2 weighted images; c, d T1 weighted images. Multiple symmetrical patches of slightly longer T1 and slightly longer T2 signals were seen in the white matter of the bilateral cerebral hemispheres and bilateral basal ganglia nuclei. Myelination of white matter is delayed. The corpus callosum is slender. The ventricular system, sulcus, fissure and pool are widened. e Fundus film of the case. The borders of the optic discs of both eyes were clear and pale, and the vascular pathways were acceptable, with cherry red spots visible in the macula. (white arrows)
Fig. 3
Fig. 3
a The mutation site of the HEXB gene. Donor loss indicates the missing site. b The diagnostic history of the patient. WES: whole-exome sequencing; CNV: copy number variants; VUS: variants of uncertain significance
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