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 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.