Jervell and Lange-Nielsen syndrome

General Information (adopted from Orphanet):

Synonyms, Signs: JLNS
Long QT interval - deafness
Number of Symptoms 20
OrphanetNr: 90647
OMIM Id: 220400
ICD-10: I45.8
UMLs: C0022387
MeSH: D029593
MedDRA: 10057936
Snomed: 373905003

Prevalence, inheritance and age of onset:

Prevalence: <= 0.9 of 100 000
Inheritance: Autosomal recessive
26702227 [IBIS]
Age of onset: Childhood
13435203 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: Familial long QT syndrome
 -Rare cardiac disease
 -Rare genetic disease
Syndromic genetic deafness
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
 -Rare otorhinolaryngologic disease


Jervell and Lange-Nielsen syndrome is a sub-type of familial long QT syndrome. It is caused by homozygous or compound heterozygous mutations on the KCNQ1 or KCNE1 genes. The disease is associated with congenital sensory deafness and a high incidence of sudden cardiac death in childhood (PMID:16461811).

Symptom Information: Sort by abundance 

(HPO:0002014) Diarrhea 22805636 IBIS 225 / 7739
(HPO:0010872) EKG: T-wave inversion 7721491 IBIS 19 / 7739
(HPO:0012266) T-wave alternans 26022593 IBIS 8 / 7739
(HPO:0001657) Prolonged QT interval Very frequent [IBIS] 100% (n=160) 20301579 IBIS 33 / 7739
(HPO:0004756) Ventricular tachycardia 9164812 IBIS 55 / 7739
(HPO:0004308) Ventricular arrhythmia 22539601 IBIS 46 / 7739
(HPO:0001664) Torsade de pointes 9164812 IBIS 15 / 7739
(HPO:0001663) Ventricular fibrillation 9164812 IBIS 35 / 7739
(HPO:0001695) Cardiac arrest Frequent [IBIS] 39% (n=186) 9164812 IBIS 87 / 7739
(HPO:0001645) Sudden cardiac death Occasional [IBIS] 27% (n=186) 20301579 IBIS 84 / 7739
(HPO:0001279) Syncope Frequent [IBIS] 9164812 IBIS 94 / 7739
(HPO:0001891) Iron deficiency anemia Frequent [IBIS] 20301579 IBIS 22 / 7739
(HPO:0002194) Delayed gross motor development 25471708 IBIS 37 / 7739
(HPO:0001250) Seizures 23668803 IBIS 1245 / 7739
(HPO:0011097) Epileptic spasms 23668803 IBIS 45 / 7739
(HPO:0002242) Abnormality of the intestine 22805636 IBIS 42 / 7739
(HPO:0008619) Bilateral sensorineural hearing impairment Very frequent [IBIS] 9164812 IBIS 23 / 7739
(HPO:0008527) Congenital sensorineural hearing impairment Very frequent [IBIS] 9164812 IBIS 165 / 7739
(HPO:0001751) Vestibular dysfunction 25471708 IBIS 19 / 7739
(MedDRA:10005545) Blood gastrin increased Frequent [IBIS] 20301579 IBIS 1 / 7739

Associated genes:


ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference
KCNE1 rs74315445 likely pathogenic RCV000148512.1
KCNQ1 rs120074186 pathogenic RCV000003275.2
KCNQ1 rs120074189 pathogenic RCV000003286.4
KCNQ1 rs120074190 pathogenic RCV000003289.2
KCNQ1 rs397508103 pathogenic RCV000003285.2
KCNQ1 rs397508110 pathogenic RCV000003281.2
KCNQ1 rs397508117 pathogenic RCV000003273.2
KCNQ1 rs397515637 pathogenic RCV000003272.2
KCNQ1 rs606231414 pathogenic RCV000144973.1
KCNQ1 rs786204778 likely pathogenic RCV000169662.1

Additional Information:

Diagnosis GeneReviews The diagnosis of Jervell and Lange-Nielsen syndrome (JLNS) is definitively established in individuals with all of the following:...
Clinical Description GeneReviews Homozygotes. Deafness is congenital, bilateral, profound, and sensorineural in all individuals with molecularly confirmed Jervell and Lange-Nielsen syndrome (JLNS) (see Deafness and Hereditary Hearing Loss Overview). ...
Genotype-Phenotype Correlations GeneReviews Data to establish better predictors for a correlation between genotype and phenotype were provided from a large number of individuals with molecularly confirmed JLNS. Among 63 individuals who were genotyped, 33% were compound heterozygotes [Schwartz et al 2006]. No clinical difference was evident between persons with at least one inactivating mutation (insertion/deletion, splice mutation, truncation) and those with missense mutations....
Differential Diagnosis GeneReviews Deafness and prolonged QTc with or without long QT syndrome (LQTS) both have multiple etiologies, including genetic and environmental causes. In many individuals with both deafness and prolonged QTc (or LQTS), the deafness and prolonged QTc (or LQTS) have separate etiologies. All of these possibilities must be considered in each affected individual, particularly in the absence of parental consanguinity or an affected sib. The following considerations are relevant in an individual who has both deafness and prolonged QTc:...
Management GeneReviews To establish the extent of disease in an individual diagnosed with Jervell and Lange-Nielsen syndrome (JLNS), the following evaluations are recommended:...
Molecular genetics GeneReviews Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED....