A 16-year-old female from a Chinese family with consanguineous parents, developed her first episode of jerks after a cold 11 years ago. The jerks involved right foot and leg without preceding sensation and was not relieved until she was given diazepam intravenously. The antiepileptic drugs (AEDs) were provided, but the episodes still occurred 3-4 times/year. The jerks were usually triggered by fatigue, emotions, or fever and lasted for minutes to hours. It could only be controlled by intravenous diazepam. She was diagnosed with "psychogenic attack" 6 years ago and was weaned off AEDs. The "psychogenic attacks" continued. Three years ago, the patient experienced loss of consciousness for minutes after right arm jerks. Six days before the admission, she developed right foot jerks after a long walk, but the jerks could not be relieved completely by diazepam. The jerks stopped with sleep without any treatment and reoccurred with waking. During the course of the disease, the patient had no intellectual disability or developmental delay, hearing loss, onychodystrophy, osteodystrophy, paresthesia, or cerebellar ataxia. She felt fatigue after running, long-distance walking, and climbing stairs. She had no remarkable medical history. Another individual in her family had similar paroxysmal episodes of leg jerks. Upon physical examination, no neurological deficit was found. MMSE test scored 29. The audiometry test was normal. The serum autoimmune panel, including anti-streptolysin "O," C-reactive protein, rheumatoid factors, immunoglobulin G, immunoglobulin M, immunoglobulin A, alexin C3, alexin C4, erythrocyte sedimentation rate, anticardiolipin antibody, anti-nuclear antibody, anti-neutrophil cytoplasmic antibody, thyroid peroxidase antibody, and thyroglobulin antibody, was negative. Both amino acid and organic acid metabolism tests of serum and urine were negative.
Continuous video electroencephalogram (EEG) monitoring showed normal background without EEG change during leg jerking. One event was captured. The patient's head and eyes deviated to the right with the right arm rising and the leg stretching straight. Then, the convulsion involved all limbs and lasted 20 s. During the event, she was alert but could not speak. The EEG showed rhythmic activity from the left frontocentral and midline regions. The activity quickly spread to the contralateral side with increased amplitude (Figure 1A). The brain MRI was reported normal. The somatosensory-evoked potential (SEP) showed remarkable reduced amplitude in the left cortex when right leg was tested. The upper limbs' SEPs were normal. Genetic analysis through an epilepsy panel of 480 genes by Kangso Medical Inspection reported a homozygous mutation in the TBC1D24 gene, c.229_240del (p.82_84del). The homozygous mutation was inherited from her healthy parents who were heterozygous, which was consistent with autosomal recessive inheritance (Figure 1B and Supplementary Figure S1). We could not predict protein function related to this mutation through SIFT, Polyphen2, or Mutation Taster analysis software.
Morphometric analysis program was performed on 3-T T1-weighted images using SPM12 toolbox in MATLAB R2011b following previously established methods. The computed output was a junction map, which highlighted abnormal structures deviating from the average normal structures based on z-score. The normal database was provided along with the MAP program. The highlighted region might correlate with gray-white blurring on the underlying MRI. The MAP analysis identified a subtle abnormality candidate with a z-score over 4, a subtle gray-white blurring in the left medial parietal region (Figure 2).
The patient was given levetiracetam with a gradually increasing dosage to 1.25 g twice/day and sodium valproate with a dosage of 0.5 g twice/day and was completely relieved several days later. Upon follow-up, the patient was weaned off the sodium valproate and did not report any symptoms in the 10-month follow-up.
Both patient and parents provided written informed consent for the study and publication.