The product of this gene is an auxiliary beta-subunit (NaVβ4) forming cardiac sodium channels, variants in which increase the late sustained sodium current. LQT13 is caused by variants in GIRK4, a protein involved in the parasympathetic modulation of the heart. Clinically, the patients are characterized by only modest QT prolongation, but an increased propensity for atrial arrhythmias. LQT14, LQT15 and LQT16 are caused by variants in the genes responsible for calmodulin (CALM1, CALM2, and CALM3 respectively). Calmodulin interacts with several ion channels and its roles include modulation of the L-type calcium current in response to calcium concentrations, and trafficking the proteins produced by KCNQ1 and thereby influencing potassium currents. The precise mechanisms by which means these genetic variants prolong the QT interval remain uncertain. Jervell and Lange–Nielsen syndrome
Jervell and Lange–Nielsen syndrome (JLNS) is a rare form of LQTS inherited in an autosomal recessive manner. In addition to severe prolongation of the QT interval, those affected are born with severe sensorineural deafness affecting both ears. The syndrome is caused by inheriting two copies of certain variant in the KCNE1 or KCNQ1 genes. The same genetic variants lead to the LQT1 and LQT5 forms of Romano-Ward syndrome if only a single copy of the variant is inherited. JLNS is generally associated with a higher risk of arrhythmias than most other forms of LQTS.
She was noted to have a heart murmur which was then discovered to be caused by a ventricular septal defect (a type of congenital heart defect), but it disappeared on its own few years after the physical examination that discovered said defect (thought to be caused by a spontaneous closure of said defect).The second case was her younger, 4-year-old toddler brother. He was born weighing 3042 grams, and was noted to have cyanosis at birth, which was an indicator for a possible heart anomaly. He learned how to control his head at 3 months of age and learned how to walk when he was 20 months old, at the age of 2 he was found to have a speech delay and could only say a handful of words. Physical examination done on him in July 1984 showed a height of 72.7 cm, a weight of 7.7 km, and a head circumference of 44.5 cm. He had the same skin tone, hair color, and facial characteristics as his proband sister. A systolic ejection murmur (grade 4/6) could be heard at his second left intercostal face, this same murmur was later discovered to be caused by pulmonary valve stenosis. Like his sister, he also had whorls and loops in his fingerprints (4 and 6, respectively), and he had routine laboratory tests and a karyotype which turned back normal. Physical examination done in him again in May 1987 showed a height of 94.3 cm, a weight of 45.2 kg, and a head circumference of 49.7 cm.