OOA (Old Order Amish)

Inheritance: autosomal recessive
Genes: KVLQT1

Inheritance: autosomal dominant
Genes: KVLQT1; KCNE1; HERG; SCN5A

JLNS1
Jervell and Lange-Nielsen syndrome
Surdo-cardiac syndrome
Prolonged QT EKG interval
Cardioauditory syndrome of Jervell and Lange-Nielsen

Prolonged QT interval
EKG changes
Deafness
Arrhythmias
Sudden cardiac death
Syncope
Seizures

Long Q-T Interval

Clinical Characteristics

General description (for patients):

This is one of two (the other being hypertrophic cardiomyopathy or HCM) diseases among plain people known to cause irregularity of the heartbeat, with risk of sudden cardiac arrest. Long QT interval refers to a finding on EKGs due to abnormal electrical conduction. One Amish family from the Southwest has been reported and the affected brother and sister were deaf as well. The latter is a feature of some but not all cases of this syndrome (the parents in this family had normal hearing). The risk of an irregular heart beat leading to the risk of sudden death can be reduced with an implanted defibrillator.

Medical description: 

The Jervell and Lange-Nielsen (JLNS1) type of prolonged QT interval is distinct from another form, namely autosomal dominant Ward-Romano syndrome, primarily in the association of deafness. Arrhythmogenic syncope and seizures occur in both disorders, often following acute stress or auditory stimuli. A number of cases have been misdiagnosed as seizure disorders for this reason. Ventricular tachyarrhythmia and ventricular fibrillation may occur and sudden cardiac death is a significant risk, even in the first decade of life.
A single Amish family with JLNS1 has been reported in which the parents, who denied consanguinity, had an affected boy and girl. However, no family information on the parents’ ancestry was reported. Hearing was clinically normal in the parents but both affected sibs were deaf (type not specified). Both parents had borderline QTc intervals of 0.43 and 0.44 while the children had values of 0.52 and 0.66.

Genetics:

JLNS1 may be an autosomal recessive disorder, caused by a mutation in KVLQT1 (11p15.5) such as in the Amish family with a novel mutation, a 2bp deletion, homozygous in the children and heterozygous in the parents.  Dominantly inherited disease can also result from heterozygous mutations in at least three potassium channel genes, KVLQT1, KCNE1, and HERG, and a cardiac sodium channel gene, SCN5A.

Treatment:

Beta-blockers such as propranolol can help prevent the arrhythmias, especially from stimulatory events. Implantable defibrillators could be life-saving in severe cases. Left stellate ganglion block or ablation has also been used.

Prognosis: 

Life span and quality of life can be normal but less so among many who suffer frequent syncopal episodes and arrhythmias due to the risk of cardiac arrest.

Ancillary treatments and support:

The primary need is for prompt diagnosis and cardiac monitoring. Patients can often be resuscitated following a syncopal attack or even cardiac arrest when prompt treatment is available.

Specialists and specilaty centers:

Cardiologist and cardiac centers.

References:

Jervell, A., and Lange-Nielsen, F.: Congenital deaf-mutism, functional heart disease with prolongation of Q-T interval and sudden death. Am. Heart J. 54: 59-69, 1957.  PubMed ID: 13435203

Chen, Q., Zhang, D., Gingell, R.L., Moss, A.J., Napolitano, C., Priori, S.G., Schwartz, P.J., Kehoe, E., Robinson, J.L., Schulze-Bahr, E., and Wang, Q. Homozygous deletion in KVLQT1 associated with Jervell and Lange-Nielsen syndrome. Circulation 99: 1344-1347, 1999.  PubMed ID: 10077519

Fraser, G.R., Froggatt, P., James, T.N. Congenital deafness associated with electrocardiographic abnormalities, fainting attacks, and sudden death. Quart. J. Med. 33: 361-385, 1964.  PubMed ID: 14176667

Resources:

Genetics Home Reference
National Organization for Rare Disorders