Gene for progressive familial heart block type I maps to chromosome 19q13.

BACKGROUND: Progressive familial heart block type I (PF-HBI) is a dominantly inherited cardiac bundle-branch conduction disorder that has been traced through nine generations of a large South African kindred. Similar conduction disorders have been reported elsewhere; however, the cause of these diseases is unknown. The aim of the present study was to determine by linkage analysis the approximate chromosomal position of the gene causing PFHBI, thereby allowing family-based diagnosis and the development of positional cloning strategies to identify the causative gene. METHODS AND RESULTS: Eighty-six members of three pedigrees, 39 members of which were affected with PFHBI, were genotyped at four linked polymorphic marker loci mapped to chromosome 19, bands q13.2-q13.3 (chromosome 19q13.2-13.3). Maximum two-point logarithm of the odds scores (which represent the logarithm of the odds ratio of detecting linkage versus nonlinkage) generated were 6.49 (theta = 0) for the kallikrein locus, 5.72 (theta = 0.01) for the myotonic dystrophy locus, 3.44 (theta = 0) for the creatine kinase muscle-type locus and 4.51 (theta = 0.10) for the apolipoprotein C2 locus. The maximum multipoint logarithm of the odds score was 11.6, with the 90% support interval positioning the PFHBI locus within a 10 cM distance centering on the kallikrein 1 locus. CONCLUSIONS: The gene for PFHBI maps to an area of approximately 10 cM on chromosome 19q13.2-13.3. There are several candidate genes in this interval; although a recombination event ruled out the myotonic dystrophy locus from direct involvement with PFHBI, the proximity of these two loci may be relevant to the observed cardiac abnormalities of myotonic dystrophy. The results provide a means of DNA-based diagnosis in the families studied and a foundation for cloning studies to identify the causative gene.

Progressive familial heart block type I. Clinical and pathological observations.

Progressive familial heart block type I (PFHB-I) is an autosomal inherited disease. It was previously postulated that the disease is limited to the cardiac conduction tissue. The presentation of a patient with dilated cardiomyopathy focused on the possibility that this might be part of PFHB-I. This observation led to routine echocardiographic examination of patients with complete heart block, who belonged to PFHB-I families, and another 5 cases with signs of dilated cardiomyopathy were identified. This is the first time, to our knowledge, that the histological picture of PFHB-I has been described. From these case reports it is clear that in the presence of a dilated cardiomyopathy the prognosis in PFHB-I tends to be poor.

Progressive familial heart block (type I). A follow-up study after 10 years.

A follow-up study was done on 55 patients, all members of families with type I progressive familial heart block (PFHB) examined during 1977. Of the 55 patients 5 had died, 17 had normal ECGs while 7 with previously abnormal ECGs remained unchanged. All the others had progressed to a more severe form of heart block and 8 of them had received permanent pacemakers. These findings again emphasize the importance of regular ECG follow-up examinations of members of PFHB families.

Progressive familial heart block. Part I. Extent of the disease.

Progressive familial heart block (type I) has been identified in the RSA. Since 1977 many families have been referred for pedigree tracing. The present probands of some 9 pedigrees are the descendants of specific children of an immigrant; other genetic diseases appear in these pedigrees. The necessity of identifying, diagnosing and possibly treating the descendants of carriers is emphasized.

Progressive familial heart block. Part II. Clinical and ECG confirmation of progression--report on 4 cases.

Two types of progressive familial heart block controlled by a single gene have been described; 4 cases show that type I is progressive and that the pathogenesis is still unknown.

Effects of nifedipine on the peri-operative ECG, as determined by continuous Holter monitoring. A double-blind study.

A double-blind study was performed on 50 elderly patients undergoing hip-replacement surgery under general anaesthesia; 26 were given nifedipine and the remaining 24 placebo to determine effects on the continuously monitored (Holter) ECG during the 4 peri-operative days. Drugs were only administered during the latter 3 days of the observation period. Surgery was performed on the morning of the 3rd day. A striking feature was the high incidence of arrhythmias in both groups of patients, a finding previously documented in both 'normal' and elderly people. A decrease in ST-segment changes was expected in the nifedipine-treated patients. An unexpected finding, therefore, was the lack of protection against cardiac ischaemic changes in the nifedipine-treated patients compared with the placebo patients. Interpretation of the ST segment as seen in the Holter-monitored ECG remains controversial. We have no clear explanation for the lack of protection against ischaemic changes. The effects of profound vasodilatation produced by nifedipine in elderly patients subjected to major surgery, general anaesthesia including administration of enflurane, and a variable amount of blood loss in the postoperative period may be important factors. In conclusion, one should perhaps be cautious of nifedipine administration under these circumstances.

What do pacemaker recipients think of their implantations? An exploratory study.

Interviews conducted with 94 pacemaker recipients were analysed to assess their knowledge and understanding of their disease and treatment, as well as to determine their self-assessment of the quality of life before and after implantation. Many patients knew little about their illness, the reason for having a pacemaker, or their prognosis. Eighteen patients claimed still to be in bad physical condition; 47 patients claimed to be physically handicapped, in 32 of whom the handicaps could be related to their cardiac condition. Fifty patients said that they were less active after implantation than before it. These findings suggest a lack of meaningful patient-doctor/doctor-patient communication. It is suggested that a team approach involving a social worker would improve continuity of care and communication, as well as the quality of patients' lives.

Holter monitoring at Tygerberg Hospital, 1979-1983--an appraisal.

Over a period of 4 years Holter monitoring was performed on 607 patients in the Division of Cardiology at Tygerberg Hospital. Indications for monitoring were broadly grouped into four categories: (i) evaluation of symptoms suggestive of disorders of cardiac rhythm (210 patients); (ii) evaluation of arrhythmias associated with a specific underlying cardiac condition (139 patients); (iii) evaluation of a previously documented or suspected arrhythmia (233 patients); and (iv) miscellaneous reasons (25 patients). Findings are presented and aspects of Holter monitoring are discussed. Finally, some recommendations for improving the clinical value of our Holter analyses are made.