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Gene Map Locus: 19q13.2-q13.3
Note: pressing the symbol will find the citations in MEDLINE whose text most closely matches the text of the preceding OMIM paragraph, using the Entrez MEDLINE neighboring function.
DeForest (1956) studied a kindred in which uncomplicated left bundle branch block occurred in 4 persons in 2 generations. Segall (1961) described an instance of father, son and daughter (of French-Canadian and black intermixture) with right bundle branch block (RBBB) and repeated Stokes-Adams attacks with various atrial arrhythmias and ventricular extrasystoles. The father died at 74 years, 14 years after the first fainting episode. Two asymptomatic brothers showed the electrocardiographic changes of Wolff-Parkinson-White. Combrink et al. (1962) described a South African family in which the mother had RBBB and died at age 35 years in a Stokes-Adams attack. Of 4 children, 3 had RBBB. The mother's parents had both died suddenly in their 30s. One of her brothers was said to have a cardiac conduction disturbance, another had dextrocardia, while 3 other sibs were apparently normal. Follow-up of this kindred revealed RBBB in 1 of 7 grandchildren (Myburgh et al., 1980). Steenkamp (1972) described a South African family in which 6 of 17 members studied showed disturbance of rhythm or conduction. Brink and Torrington (1977) suggested that the disorder they referred to as progressive familial heart block, type I, is prevalent in South Africa and is the same disorder as that reported by Combrink et al. (1962) and Steenkamp (1972). Type I heart block in their description tends to have the pattern of a right bundle branch block and/or left anterior hemiblock, manifesting clinically when complete heart block supervenes with syncopal episodes, Stokes-Adams seizures, or sudden death. The risk to life appeared to be greatest at or soon after birth, during puberty and the early twenties, and again toward middle age. (In contrast to this form of progressive familial heart block, type II is characterized by sinus bradycardia and left posterior hemiblock progressing to complete heart block; the QRS complexes are narrow rather than wide as in type I. See 140400.) In two studies, van der Merwe et al. (1986) and van der Merwe et al. (1988) provided follow-up information on the kindred reported by Brink and Torrington (1977) and documented progression of the disorder.
Greenspahn et al. (1976) presented evidence suggesting that a susceptibility to disorder in conduction that is expressed late in life is inherited. Stephan (1978) reported a Lebanese kindred descended from a man who died presumably with heart block and who left more than 260 descendants by 3 wives. Of the 209 family members examined, 32 showed abnormalities of the conduction system: complete RBBB in 12, incomplete RBBB in 7, RBBB with left axis deviation in 6, RBBB with right axis deviation in 4, and complete heart block in 2. These families may represent a heterogeneous group of conduction disturbances, distinct from conditions in which a specific conduction defect occurs (e.g., 113950, 115080). Lorber et al. (1988) observed a father and 2 sons with an electrocardiographic pattern of pseudo left posterior hemiblock and incomplete right bundle branch block that resulted in right axis deviation.
Brink et al. (1995) did linkage studies in the kindred reported by Brink and Torrington (1977) and demonstrated that the gene for progressive familial heart block, type I (PFHB1) maps to 19q13.2-q13.3. They pointed out that this large kindred descended from an ancestor who emigrated from Portugal in 1696. It had been estimated that there may be between 1,000 and 9,000 gene carriers among his descendants. Maximum 2-point lod scores were 6.49 at theta = 0.0 for kallikrein (KLK1; 147910), 5.72 at theta = 0.01 for the myotonic dystrophy locus (DM; 160900), 3.44 at theta = 0.0 for the creatine kinase muscle-type locus (CKM; 123310), and 4.51 at theta = 0.10 for the apolipoprotein C2 locus (APOC2; 207750). Brink et al. (1995) noted that the gene for myotonin protein kinase, which is implicated as a cause of myotonic dystrophy, lies within this region and that myotonic dystrophy is a disease complicated by heart block and other conduction abnormalities. A recombination event ruled out the myotonic dystrophy locus from direct involvement with PFHB1.
Stephan et al. (1997) provided follow-up on the Lebanese kindred reported earlier by Stephan (1978). They considered the most appropriate designation for this disorder to be 'hereditary bundle branch defect' (HBBD). Mapping of the disorder in this family to 19q was achieved by de Meeus et al. (1995), thus confirming the findings of Brink et al. (1995). An autopsied case was reported by Stephan et al. (1985). The founder of the Lebanese kindred was a polygamous ancestor who engendered more than 400 descendants in 5 generations. Stephan et al. (1997) studied the evolution of the disorder in this kindred over a 2-decade period, described a variety of electrocardiographic abnormalities encountered in the family, and reassessed penetrance. A total of 396 persons had at least one clinical examination and ECG of whom 47 were judged affected and 36 'indeterminate.' The conduction block may be overt in the first year of life, and among affected individuals there was a worsening of the conduction block in 5% to 15% of cases, leading to complete atrioventricular block and possibly to sudden death. A group of individuals had QRS anomalies in right precordial leads, possibly indicating partial right bundle branch block. A high proportion of these were identified as mutation carriers and about one-fifth of these patients evolved toward a complete fascicular block. By contrast, mutation carriers with a normal electrocardiogram remained normal. Mutation carriers demonstrated a conduction block significantly more often in males than females (75% and 50%, respectively). Brink et al. (1994, 1995) had found almost 100% penetrance in their South African family. Stephan et al. (1997) presented a table of penetrance values estimated from 9 other families as well as their own.
This is undoubtedly the disorder in the family reported by Husson et al. (1973) in which a girl had complete heart block at age 2 years and died at age 10 with ventricular fibrillation. A brother had right bundle branch block at age 15 years and complete heart block at age 17. A sister, aged 17 years, had prolonged intraventricular conduction time with incomplete right bundle branch block. In this family, complete heart block and bundle branch block were expressions of the same genotype.
Victor A. McKusick - updated : 5/16/1997
Victor A. McKusick : 6/4/1986
terry : 7/31/1998
alopez : 6/26/1997
alopez : 6/10/1997
alopez : 5/20/1997
terry : 5/16/1997
mark : 5/11/1995
terry : 5/13/1994
mimadm : 4/9/1994
carol : 10/26/1993
supermim : 3/16/1992
carol : 1/8/1991
Select Entry from OMIM Database. |
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This table is not part of the normal OMIM Entry Page. |
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m.hill@unsw.edu.au
Date Last Modified: 11/3/99
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