| Locus (OMIM) | Gene (OMIM) | Inheritance | Key Locus References (PubMed) | Key Gene References (PubMed) | Evidence (ClinGen)  |
|---|---|---|---|---|---|
| JLNS1 | KNCQ1 | Autosomal Recessive | Neyroud et al., 1997 | Neyroud et al., 1997 | Definitive |
| JLNS2 | KCNE1 | Autosomal Recessive | Tyson et al., 1997; Schulze-Bahr et al., 1997 | Tyson et al., 1997; Schulze-Bahr et al., 1997 | Moderate |
Within the inner ear, endolymph homeostasis is controlled in part by the delayed rectifier potassium channel. This channel is formed by proteins encoded by the KVLQT1 and KCNE1 genes. A deletion-insertion mutation in three affected children in two families in KVLQT1 was demonstrated by Neyroud et al., (1997). Tyson et al., (1997) identified a family in which affected children were homozygous-by-descent for a mutation in KCNE1. The phenotypes associated with these mutations were indistinguishable and were characterized by prolongation of the QT interval, torsade de pointe arrhythmias (turning of the points, in reference to the apparent alternating positive and negative QRS complexes), sudden syncopal episodes, and severe-to-profound sensorineural hearing loss. Heterozygotes have Romano-Ward syndrome, which unlike JLN syndrome, does not include severe-to-profound hearing loss in the phenotype.