A 12-year-old boy presented with a new onset generalized tonic-clonic seizure. He is the first child of a phenotypically normal mother. The patient was born at term after an uneventful pregnancy by an uncomplicated caesarean section with low birth weight of 2,900g (10–25th percentile). At 8 months the child underwent surgical repair of a cleft palate and at age 2 years had two episodes of febrile convulsion. He had a learning disability in his school-aged years. On family history, his father had a prominent forehead, small down-turned mouth, micrognathia, and nasal voice (). He had not undergone any prior specific evaluation, but seemed to have normal intelligence without any neuropsychiatric symptoms including a seizure history.\nPhysical examination revealed prominent forehead, small down-turned mouth, micrognathia (), and repaired cleft palate with not well formed uvula (). His height was 146 cm (25–50th percentile) and weight was 38.5 kg (25–50th percentile). Chvostek’s and Trousseau’s signs were negative. He had mild mental retardation with an intelligence quotient (IQ) of 68 on the Korean version of Wechsler Intelligence Scale for Children (K-WISC).\nThe electrocardiogram (ECG) was abnormal due to a prolonged corrected QT interval and the chest radiograph failed to show a thymus shadowing. Computed tomography (CT) of the heart revealed right aortic arch (), and CT of the brain showed multiple calcifications in the bilateral basal ganglia and both frontal white matters (). The electroencephalogram (EEG) revealed generalized intermittent slow waves without any epileptiform discharges.\nLaboratory tests showed hypocalcemia (calcium 6.5 mg/dL, ionized calcium 2.8 mg/dL), hyperphosphatemia (9.1 mg/dL) and normal level of magnesium (1.8 mg/dL). Parathyroid hormone (PTH) was decreased to 4.76 pg/mL (reference range 15–65 pg/mL) and 25-vitamin D3 was decreased to 13.6 ng/mL (reference range 30–60 ng/mL). Peripheral blood count, hepatic, renal and thyroid function tests were all normal except thrombocytopenia (144,000/μL). Immunological studies showed normal levels of Immunoglobulins but T cell subpopulation analysis was abnormal. T lymphocyte was decreased to 42.8 %/μL (reference range 52–78%/μL), CD4/CD8 T cell ratio was decreased to 0.79 (reference range 0.8–3.0).\nFluorescent in situ hybridization (FISH) analysis was performed using peripheral blood and chromosomal study was carried out using DiGeorge/VCFS TUPLE1 region probe (22q11.2) with an ARSA control probe (22q13) which confirmed a 22q11.2 deletion. His father revealed the same chromosomal abnormality, which suggests paternal inheritance in this case.\nThe patient was treated with calcium citrate and calcitriol. He remained asymptomatic with normalization of his serum calcium level with medications.
A 44-year-old woman was admitted to hospital for further evaluation of recurrent episodes of syncope with a long QT-interval associated with hypocalcaemia. The patient had experienced epileptic seizures as a child, but no treatment had been required. No further epileptic events were reported after puberty. Otherwise, past medical and surgical history was unremarkable. The patient denied taking recreational drugs or consuming alcohol. There was no history of inherited diseases among relatives.\nThe patient experienced her first syncope episode in 2014 while she was doing housework; this occurred without any prodrome or signs of vasovagal reaction (i.e. fainting, nausea, sweating, blurred vision, tingling of lips or fingertips). The fall caused by the syncope led to a fracture of the atlas arch and she was admitted to the hospital. On admission, vital parameters were oxygen saturation 98%, blood pressure 124/65 mmHg, heart rate 80/min; there was no cyanosis, oedema, or bibasilar rales in the lungs. She was awake and oriented, with no focal neural deficits. Cranial computed tomography (CCT) ruled out cerebral pathologies. The electrocardiogram (ECG) on admission showed a prolonged QT interval with corrected QT (QTc) of 520 ms, associated with a hypocalcaemia (calcium level 1.4 mmol/L) (). Echocardiography showed apical hypokinesia and coronary angiography revealed normal coronary arteries. Cardiac magnetic resonance tomography ruled out structural heart disease and there were no signs of myocarditis. Serial ECG showed a normal QTc when serum calcium levels were within the normal range. No significant arrhythmias were documented on 7-day-Holter monitoring.\nHypocalcaemia was interpreted as part of a newly diagnosed primary hypoparathyroidism, and substitution therapy with vitamin D (1000 U/day) and calcium (500 mg twice daily) was started. However, the patient admitted to not having taken medication shortly before a second syncope event that occurred suddenly at home in 2019, which resulted in fracture to the jaw and hand. Physical and emotional stress at that time were denied. Physical examination including neurological assessment was unremarkable. CCT revealed neither intracranial bleeding nor an ischaemic event. Levetiracetam 500 mg twice a day was prescribed by neurologist due to an increased epileptic activity on electroencephalography. In the absence of other possible causes, this event was assumed to also be related to hypocalcaemia.\nECG on admission to our hospital () showed no significant conduction disorders and no repolarization abnormalities. Telemonitoring was unremarkable except for a single 3-min episode of a self-terminated supraventricular tachycardia with sudden onset and a heart rate of 140 beats/min without any haemodynamic compromise. Laboratory tests showed hypocalcaemia (1.76 mmol/L) due to reduced parathormone production; all other electrolytes were within normal ranges; haemoglobin was 12 mg/dL. High-sensitivity troponin was not elevated. Although it had not previously been documented, we noted mild facial dysmorphia (i.e. prominent nose with large tip and hypoplastic nares, small dysmorphic ears). The combination of transient hypocalcaemia with subtle facial characteristics were thought to be indicative of one of the velocardiofacial syndromes, namely DiGeorge syndrome. Subsequent genetic test showed a microdeletion in 22q11.2, confirming the diagnosis ().\nThere are two possible mechanisms of hypocalcaemia inducing a TLOC: arrhythmogenic syncope or seizure. Because our patient showed prolonged QTc immediately after the first episode, we assumed that she had experienced an arrhythmogenic syncope, and that this was caused by a hypocalcaemia-induced long QT syndrome. Therefore, it was decided to implant an event recorder for the detection of arrhythmic events. Substitution therapy with calcium carbonate 500 mg twice daily and vitamin D 1000 U/day was initiated. The calcium level was monitored every 3 months and dosages adjusted by an endocrinologist as required. The patient was also examined by neurologist. Although we made a strong recommendation for psychiatric evaluation, the patient declined. No further organ systems were affected. No recent syncope was reported during 12 months of follow-up and there were no arrhythmic events stored by the event-recorder.