We report a case of White-Sutton syndrome in a 2-year-old girl. She was the second child of healthy and unrelated Chinese parents. She was born at 39 weeks of gestation by cesarean section, with a birth weight of 2840 g. The mother had gestational diabetes mellitus. The patient had a 20-year-old brother who was healthy, and her family history was negative for heart disease, epilepsy, and other neurological disorders. Nineteen hours after delivery, the girl was admitted to the neonatal unit due to repeated vomiting and diagnosed with digestive tract bleeding, which was managed with fasting and thrombin. The passage of meconium was not delayed, but abdominal distension was observed from 4 days after birth and persisted. Abdominal ultrasound showed a dilated bowel and bowel gas. Abdominal distension recurred several times over the next 2 years, culminating in mechanical ileus at the age of 1 year. Mechanical ileus was improved by fasting, gastrointestinal decompression, and glycerin enema. At the age of 5 months, the patient was diagnosed with an atrial septal defect (18 × 23 × 22 mm), and pulmonary arterial hypertension (42 mmHg) was recorded for the first time. Atrial septal defect closure surgery was performed when the patient was 5 months of age, and the patient was treated with digoxin (0.1 mg/kg.d), spironolactone (2.4 mg/kg.d), and hydrochlorothiazide (0.8 mg/kg.d) after surgery. The patient had recurrent pneumonia after surgery and was admitted to the ICU 6 months after surgery for heart failure. Her left ventricular ejection fraction dropped to 22% at the lowest recording. At the 1-year follow-up after ICU discharge, the patient’s left ventricular ejection fraction ranged from 47 to 55%. At the age of 9 months, she presented with epileptic spasm with hypsarrhythmia several times a day. She was successively treated with courses of topiramate (TPM; maximum dosage of 5 mg/kg.d), valproate (VPA; maximum dosage of 24 mg/kg.d), and cocktail therapy. No obvious seizure attack was observed between the ages of 13 and 19 months after combined treatment with TPM, VPA and cocktail therapy, which was a combination nutraceutical therapy consisting of vitamin B1 50 mg/d, vitamin B2 100 mg/d, vitamin C 200 mg/d, vitamin E 100 mg/d, L-carnitine 1000 mg/d, and coenzyme Q10 100 mg/d. At 19 months old, seizure returned, occurring several times a day, and did not improve with successively administered courses of levetiracetam (LEV; maximum dosage of 20 mg/kg.d), vigabatrin (VGB: the maximum dosage of 160 mg/kg.d), nitrazepam (NZP: the maximum dosage of 0.07 mg/kg.d) and clobazam (CLB; maximum dosage of 0.27 mg/kg.d). Adrenocorticotropic hormone (ATCH, 1.5 IU/kg) was added to the combined levetiracetam, vigabatrin and cocktail therapy for 2 weeks when the patient was 1 year and 10 months old. Thereafter, prednisone was continued before being gradually reduced and withdrawn over 1 month. The frequency of seizures decreased to two times per week. From 1 year of age, the patient suffered from sleep disturbance, which mainly manifested as light sleep, often crying in sleep, and being difficult to soothe. The patient had several dysmorphic features, including a high-arched palate, frontal bossing, a congenital preauricular fistula, a tented mouth, a broad nasal root, a flat nasal bridge, and tongue protrusion. Brain magnetic resonance imaging performed at 1 year showed cerebral atrophy associated with enlargement of the supratentorial ventricles, thinned corpus callosum, and delayed myelination. She did not pass the newborn hearing screening conducted with otoacoustic emissions testing, and hearing loss was confirmed by otoacoustic emissions testing at the age of 1 year. Peripheral venous blood samples were collected from the proband and her parents with their informed consent. Chromosomal microarray analysis for the proband was performed using Affymetrix Cytoscan 750 K. The results of the chromosomal microarray analysis and mitochondrial genetic testing for the proband were normal. The results of prenatal karyotype analysis on a cord blood sample also were normal. Trio-based WES revealed that the POGZ gene had a de novo heterozygous frameshift mutation [NM_015100.4:c.2746delA (p.Thr916ProfsTer12)], which was not found in current population databases (dbSNP, GnomAD, and ExAC). Most previously reported mutations in the POGZ gene are null variant [,, ]. According to the guidelines of the American College of Medical Genetics and Genomics (ACMG) and the Association of Molecular Pathology (AMP), the variant identified in the present case is considered pathogenic. At the last follow-up at 2 years of age, the patient was experiencing a seizure every 3–5 days. Her parents had stopped all anti-seizure medications against medical advice, and she was receiving traditional Chinese massage. Developmentally, she could turn over, sit without support, make eye contact, and laugh, but could not stand or speak.