Patient 1, a female aged 10 years and 4 months, is the first of two children of a healthy 38-year-old woman and a non-consanguineous 48-year-old man, whose family history was unremarkable. She was conceived naturally. The fetal ultrasound scan at gestational week (gw) 12 was normal, while at gw 21 a choroid plexus cyst and echogenic intracardiac focus were detected, the biparietal diameter was at the 95th centile at gw 21 and >95th centile at gw 33 with normal cerebral morphology. She was born at the 34th gw with a weight of 3080 g (90-97th centile), length of 49 cm (90th centile) and head circumference of 35.6 cm (97th centile). At birth, a diffuse capillary malformation involving the trunk and limbs was observed, associated with cutaneous syndactyly of the 2nd and 3rd toes (). During the first year of life, a plantar epidermal nevus and a small hemangioma, which subsequently disappeared, were observed, together with left hemihyperplasia (detected at the age of 3 months).\nCardiac and abdominal ultrasound scans were repeatedly normal. Brain MRI scans detected increased peritrigonal signal of white matter at the age of 10 months and focal hemimegalencephaly with perisylvian polymicrogyria at the age of 7 years. From the age of 7 years, the girl had episodes of generalized tonic-clonic seizures refractory to antiepileptic therapy. She suffers from mild cognitive impairment and attention deficit disorder, and in the last years had temper tantrums and angry outbursts.\nOn physical examination at the age of 10 years and 4 months, her weight was 35 kg (25th-50th centile), height 138 cm (25th-50th centile) and head circumference 60 cm (+ 5.2 SD). She had left hemihyperplasia, involving face, trunk and limbs (mainly legs) with diffusely soft and thick irregularly marbled skin and prominent capillaries and veins on the trunk, abdomen and limbs. Three small (diameter <0.5 cm) achromic spots were observed on the trunk. Her 3rd right finger was significantly larger than the contralateral one and she had a bilateral proximal 4/5 cutaneous syndactyly of the 2nd and 3rd toes. Besides macrosomia, she had dysmorphic features including malar hypoplasia, hypertelorism (inner canthal distance >97th centile, palpebral length + 1 SD), long philtrum (>97th centile) and high palate, and S-shaped scoliosis.
A 57-year-old Asian woman experienced an abnormal feeling on the left side of her neck and difficulty breathing 90 minutes after eating a Chinese noodle dish containing roasted pork, egg, spinach, seasoned bamboo shoots, laver, and garlic. She was advised to call an ambulance by our triage nurse after telephone consultation and was transported to our hospital by a physician-staffed helicopter due to the long distance from her house to the hospital. She had a history of removal of a left sphenoid ridge meningioma one year earlier. She had experienced limited rigidity of her left neck and limited peripheral cold sensation on her left side in winter since approximately 10 years of age. She had experienced limited peripheral swelling of her left side and limited lower back pain of unknown origin on her left side several times. She had been suffering from oral allergy syndrome since she was young. She sometimes experienced a tingling sensation on her lips and an unpleasant feeling in her throat after eating some types of fruit. Those fruits included mandarins, oranges, kiwis, bananas, and pineapples. She was married but did not have any children.\nOn arrival, 180 minutes after eating the noodles, she had clear consciousness, and her blood pressure was 130/90 mmHg, her heart rate was 80 beats per minute, her percutaneous oxygen saturation was 100% under room air, and her body temperature was 36.9°C. She had left neck and chest swelling without color change. Her breathing difficulty subsided spontaneously.\nThe results of a blood analysis were as follows: white blood cells, 6,000/mm3; hemoglobin, 14.8 g/dL; platelets, 38.3 × 104/mm3; aspartate aminotransferase, 15 IU/L; alanine aminotransferase, 11 IU/L; total bilirubin, 0.5 mg/dL; total protein, 6.7 g/dL; glucose, 118 mg/dL; blood urea nitrogen, 18.9 mg/dL; creatinine, 0.90 mg/dL; amylase, 63 IU/L; creatine phosphokinase, 89 IU/L; sodium, 142 mEq/L; potassium, 4.0 mEq/L; chloride, 106 mEq/L; C-reactive protein, 0.05 mg/dL; prothrombin time, 10.6 (control, 11.9) sec; activated partial thrombin time, 26.4 (control, 26.9) sec; fibrinogen, 310 mg/dL; fibrin degradation products, 0.8 μg/mL; troponin T, 0.06 (0-0.14) ng/mL; and immunoglobulin E (IgE), 429 (0-250) IU/mL. Chest roentgen, an electrocardiogram and cardiac echography findings were all negative. Neck computed tomography (CT) with contrast medium and magnetic resonance imaging (MRI) revealed left-side-limited edema in the subcutaneous area and surrounding esophagus and bronchus (Figures , ).\nThese radiological findings excluded hemorrhaging or pseudoaneurysm formation. She underwent observational admission. After her edema improved, she was discharged on the third hospital day. A follow-up examination one week later showed complete resolution of the neck and chest edema. The results of a blood allergen test analysis (0-1.39) showed an elevated immunoglobulin E (IgE) level as follows: Japanese cedar, 44.30; betula alba, 7.27; orchard grass, 3.42; Japanese cypress, 2.65; dermatophagoides farina, 3.03; house dust, 1.85; and mugwort, 1.70. The remaining allergens were within the normal ranges, as follows (0-1.39): alder 1.35, timothy 0.85, 0.33; cat skin, 0.25; and Candida, 0.22. The results for the following allergens were all zero: ragweed, Alternaria, dog skin, wheat, buckwheat, soybean, rice, tuna, salmon, lobster, crab, milk, beef, chicken, pork, albumen, ovomucoid, peanut, sesame, kiwi, banana and latex. We also obtained blood samples from the bilateral upper extremities at the same time. The examination items that showed ≥5% laterality were as follows: white blood cell count (6,500/mm3 vs. 6,100/mm3), platelets (40.8 × 104/mm3 vs. 38.0 × 104/mm3, aspartate aminotransferase (12 IU/L vs. 11 IU/L), lactate dehydrogenase (184 IU/L vs. 172 IU/L) and creatinine (0.63 mg/dL vs. 0.58 mg/dL). We could not obtain permission from the patient for further a genetic analysis by skin biopsy.