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.
A 26-year-old Thai man without underlying disease came to emergency unit because of carpopedal spasm for 4 hours. He also reported numbness and tingling at perioral area and muscle cramps in both legs. The patient's history of birth and development was normal, and he had been previously healthy. He had no history of recurrent infection or cardiac disease. He had attended 6 years of elementary school, and is working as an unskilled laborer. He did not drink alcohol or use illicit drugs. There was unremarkable family history.\nOn examination, the patient was alert. His height was 153 cm (<3rd centile) and his weight was 65 kg (body mass index =27.77 kg/m2). His blood pressure was 100/60 mm Hg and pulse was 80 beats per minute. He had bilaterally carpopedal spasm and positive Chvostek's sign. Cardiac, chest, and abdominal examinations were unremarkable. He had no subcapsular cataract. Laboratory investigations showed hypocalcemia with calcium level of 1.5 mmol/L (normal range, 2.2–2.53 mmol/L), ionized calcium level of 0.7 mmol/L (normal range, 1.09–1.3 mmol/L), and hyperphosphatemia with phosphate level of 1.68 mmol/L (normal range, 1.07–1.49 mmol/L). Serum PTH level of 24.2 pg/mL (normal range, 15–65 pg/mL) was inappropriately normal during severe hypocalcemia. Serum magnesium and creatinine level were normal. Complete blood count and other biochemistry tests were also within normal limit. According to laboratory findings, hypocalcemia secondary to hypoparathyroidism was diagnosed. His electrocardiogram revealed prolonged QT interval with corrected QT interval of 473 msec (normal < 450 msec in male) and no ST-T change. Intravenous infusion of 10% calcium gluconate with bolus dose and continuous rate of 1 mg of elemental calcium/kg/hr was administered with concomitant oral calcium and vitamin D analogues.\nTo search for the cause of hypoparathyroidism, he had no history of neck surgery or irradiation. Morning serum cortisol level, thyroid function test, and hemoglobin A1C were normal, polyglandular autoimmune syndrome is less likely. At first presentation, we did not recognize any dysmorphic features. However, minor facial abnormalities were detected by meticulous examination. He had a prominent forehead, hypertelorism, hooded eyelids, ear microtia, low set ear, thick and overfolded ear helix, left external auditory canal stenosis, broad nasal bridge, and prominent lips (). His intelligence quotient or IQ by Wechscler Adult Intelligence Scale was 69, which categorized as mild mental retardation. Primary hypoparathyroidism along with dysmorphic face and mild mental retardation lead to suspicion of chromosome 22q11.2 deletion syndrome in this patient. Conventional chromosome analysis using the standard G band procedure showed a normal male karyotype. Subsequently, Array Comparative Genomic Hybridization (CGH) analysis was performed using Agilent custom-designed 44 K oligonucleotide array. The array contains more than 41,000 oligonucleotide probes and has both genome-wide coverage and dense coverage in regions of known microdeletion/duplication syndromes, subtelomeric and pericentromeric regions (Genzyme Genetics, Monrovia, CA). The CGH array showed a copy loss of 192 oligonucleotide probes in the region of 22q11.2 (genomic coordinates 17289032–19687983), with an estimated size of approximately 2.40–3.14 Mb at 22q11.21 region. The 22q11.2 deletion was confirmed by a fluorescent in situ hybridization (FISH), using the HIRA probe (Abbott Molecular). The deleted region contains approximately 34 OMIM genes. Further investigations included transthoracic echocardiography, renal ultrasonography, and dental examination were all normal. Audiography showed bilateral conductive hearing loss. CT brain found bilateral basal ganglion calcification. Finally, he was diagnosed with chromosome 22q11.2 deletion syndrome (microdeletion). Genetic counseling was informed to him and his family. He was discharged from the hospital with 1,000 mg elemental calcium as calcium carbonate and 0.25 μg alfacalcidiol twice daily. The serum calcium level was maintained in lower normal range to prevent hypercalciuria. During subsequent follow-up, the patient did not have any recurrence of hypocalcemic symptom.