To explore the clinical characteristics of congenital long QT syndrome (LQTS) in children.

A 10-year-old male child (proband) diagnosed with type 2 LQTS (LQT2) at Chengdu Women′s and Children′s Central Hospital in July 2021 was enrolled. Clinical data from the proband and his 8 family members (mother, father, younger brother, maternal grandfather, maternal grandmother, paternal grandfather, paternal grandmother, maternal uncle) were collected. A pedigree map for LQTS genetic investigation of families of proband was constructed. Whole exome sequencing (WES) followed by Sanger sequencing validation were performed on the proband and parents to identify pathogenic variants. Sanger sequencing of the identified variant was conducted in selected family members. Based on the clinical data and genetic findings of the proband and his family members, the diagnosis and management of congenital LQTS were analyzed. This study was approved by the Medical Ethics Committee of Chengdu Women′s and Children′s Central Hospital [Approval No. Lun Shen 2021 (118)], and informed consent form was obtained from the child′s guardian.

① Both the proband (male, 10 years old) and the mother (31 years old) had a history of recurrent syncope, their electrocardiogram results showed a corrected QT interval (QTc) >500 ms and notched or biphasic T-waves. The proband′s maternal grandfather died of liver cancer at the age of 49, with no documented history of syncope or available electrocardiogram records. Other family members, except the proband′s mother, had no history of syncope, and their electrocardiogram results revealed normal QTc. ② WES revealed a heterozygous missense mutation of KCNH2: c. 94G>A (p.A32T) in the proband and his mother, confirming maternal inheritance. The variant was absent in the proband′s younger brother, father, maternal uncle, and maternal grandmother. ③ Both the proband and his mother were diagnosed of LQT2 subtype. The proband was treated with oral propranolol hydrochloride, while his mother received combined oral therapy with propranolol hydrochloride and mexiletine hydrochloride, both need taking lifelong medicine. The proband and his mother had been treated and followed up for over 3 years, and no syncope and cardiac events had occurred. The recheck of electrocardiogram showed that the proband′s QTc was shortened and his mother′s QTc returned to normal.

Family investigation facilitates early identification of congenital LQTS patient. Electrocardiogram examination with accurate QTc measurement is critical in syncope evaluation to prevent missed diagnoses of LQTS patient. Beta blockers are effective in the treatment of congenital LQT2 subtype patients.