Case report: Misdiagnosed orolingual dyskinesia as a consequence of seizures in a chorea-acanthocytosis patient with a novel VPS13A variation from a family with consanguineous marriage

Abstract

Chorea-acanthocytosis (ChAc) is a rare autosomal recessive inherited syndrome with heterogeneous symptoms, which makes it a challenge for early diagnosis. The mutation of VPS13A is considered intimately related to the pathogenesis of ChAc. To date, diverse mutation patterns of VPS13A, consisting of missense, nonsense, and frameshift mutations, have been reported. In this study, we first report a clinical case that was misdiagnosed as epilepsy due to recurrent seizures accompanied by tongue bite for 9 months, which was not rectified until seizures were controlled and involuntary orolingual movements with awareness became prominent and were confirmed to be orolingual dyskinesia. The patient was eventually diagnosed as ChAc based on whole-exome sequencing revealing novel homozygous c.2061dup (frameshift mutation) and c.6796A > T dual mutations in VPS13A. The patient from a family with consanguineous marriage manifested epileptic seizures at onset, including both generalized tonic-clonic seizures and absence but normal long-term electroencephalography, and gradually developed orofacial dyskinesia, including involuntary tongue protrusion, tongue biting and ulcers, involuntary open jaws, occasionally frequent eye blinks, and head swings. The first test of the peripheral blood smear was negative, and repeated checks confirmed an elevated percentage of acanthocytes by 15-21.3%. Structural brain MRI indicated a mildly swollen left hippocampus and parahippocampal gyrus and a progressively decreased volume of the bilateral hippocampus 1 year later, along with atrophy of the head of the caudate nucleus but no progression in 1 year. We deeply analyzed the reasons for long-term misdiagnosis in an effort to achieve a more comprehensive understanding of ChAc, thus facilitating early diagnosis and treatment in future clinical practice.

Keywords: VPS13A; chorea-acanthocytosis; deep brain stimulation; epilepsy; orolingual dyskinesia.

Figure 1

(A) Swollen left hippocampus and parahippocampal gyrus on axial T1, T2, and T2 FLAIR sequences and hyperintensity on T2 FLAIR sequences. (B) Atrophy of the head of the caudate nucleus and resulting enlarged anterior horn of the lateral ventricle on axial T1, T2Flair, and sagittal T1 sequences. (C) Decreased volume of the bilateral hippocampus and enlarged bilateral temporal horn of the lateral ventricles. (D) Almost the same degree of atrophy of the head of the caudate nucleus compared with last year. [(A,B) First structural brain MRI. (C,D) Reexamined structural brain MRI 1 year later. All images are marked by red arrows].

Figure 2

Acanthocytes on the second peripheral blood smear [(A), red arrows] and the third peripheral blood smear [(B), red arrows].

Figure 3

WES followed by confirmation by family verification, revealed the homozygous genotype of the patient and his brother and the heterozygous genotype of his parents and sister in the c.2061dup mutation of VPS13A.

Figure 4

Pedigree chart of the affected family. Double lines indicate consanguineous unions. Square denotes a male family member, the circle represents a female family member, the slashed symbol indicates a deceased family member, the fully shaded symbol shows the patient with epilepsy, and the open symbol presents no symptoms. Arrow: index patient. Asterisk: genetic testing performed. Aa, heterozygous; aa, homozygous for c.2061dup (p. Leu688fs) in VPS13A.