Mehnaz Atiq ( Department of Paediatric Cardiology, National Institute of Cardiovascular Diseases, Karachi. )
Kalimuddin Aziz ( Department of Paediatric Cardiology, National Institute of Cardiovascular Diseases, Karachi. )
Familial cardiac conduction disorder of a progressive nature has been reported in adult and paediatric patients1-4. An underlying cardiomyopathy was found in most of these patients, either of hypertrophic1,2, restrictive5 or dilated variety3. Systemic diseases like juvenile rheumatoid arthritis and other collagen disorders and familial dysautonomia infrequently have associated conduction abnormalities6-9. We present a family in which four of seven siblings had abnormalities of cardiac conduction and no concomitant
cardiomyopathy or systemic disease. Additionally, there was an association of multiple bony exostoses in six siblings and deafness in two (Table I). The purpose of this presentation is to highlight the association of two familial abnormalities in one family.
SM, a thirteen year old boy, previously asymptomatic, presented with one ‘day’s history of syncope and tonic-clonic seizures occurringfour hours pnorto admission. Clinically, he was afebrile, had a heart rate of 30/min, a respiratory rate of 30/min and a blood pressure of 90/60 mm of Hg. He also had multiple exostoses around the wrists and elbowjoints and had a severe bilateral conductive hearing loss of 90 decibels at a 2000 hertz frequency. The electrocardiogram showed complete heart block with atrial rate of 100 beats/min and ventricular rate of 25’ beats/mm with a QRS duration of 0.12 seconds (Table II).
The echocardiography showed no structure and function abnormality in the heart, the left ventricular diastolic dimensionbeing 37 mm, systolic dimensionbeing 25 nun and the ejection fraction was 70% (normal 62-85%). The serum sodium was 134 meq/l, serumpotassium was 4.2 meq/l, serum calcium was 9.4 mg/dl and serum cardiac enzymes were normal. Initially, he was managed with isoproterenol infusion ma dosage of 0.05 ug/kg/min and twenty-four hours laterwith a temporaiy pacemaker. Unfortunately he succumbed to staphylococcus aureus septicaemia ten days later.
U.M., a ten year old boy, presented to the emergency room withvomitingand abdominal pain. The heart rate was 25 beats/min, the respiratoiy rate was 40/min and the blood pressure was 50/30 mm of Hg. He had multiple bilateral exostoses around wrist, elbow, knee and ankle joints (Figure 1).
The hearing test was normal in this patient. The electrocardiogram showed a complete heart block (Table II) with atrial rate of 150 beats/min and the ventricular rate of 25 beat/min. The echocardiography showed a left ventricular diastolic dimension of 39 mm, systolic dimension of 25 nun and the ejection fraction of 73% (normal 62-85%). The serum sodium was 138 meq/L, serum potassium was 3.8 meq/L, serum calcium was 10.1 mg/dl. He had normal cardiac enzymes and the screening for collagen disorder was normal. The initial’ drug therapy included dopanune infusion in a dosage of 10uig/kg/min and a temporary pacemakerwhich was laterreplacedby an epicardial VVl permanent pacemaker. The patient has remained well thereafter.
Case3 and 4
JM and NM are eleven and nine year old boys respectively and are asymptomatic. They were screened for cardiac conduction defects and multiple exostoses. Both had exostoses of ends of long bones. Their electrocardiograms showed sinus rhythni and a heart rate of 70 beats/mm and 80 beats/min respectively (Table II). There was a left bundle branch block in both and a left axis duration in 3M and right axis deviation in NM. After two years, the rhythm of 3M deteriorated and he developed a first degree heart block, irregular heart rhythm with atrial extra systoles in addition to the left bundle branch block (bifasicular block). The echocardiography, serum electrolytes, serum calcium, cardiac enzymes and antinuclear antibodies were nonnal in both. Hearing tests revealed that 3M had a conductive hearing loss of 60 decibels at 2000 hertz frequency, whereas NM had a normal hearing.
Case 5,6 and 7
RF, a seven year old girl: AM and MM, three and five year old boys were also screened. RF and MM had multiple exostoses (Figure 2),
whereas, AM did not. All the three had nonnal electrocardiograms, a normal cardiac function on echocardiography and normal serum electrolytes, calciumand cardiac enzymes. Antinuclear antibodies and hearing tests were not perfonned..
Other family members
Mother, father and maternal grandmother did not have any abnormality on electrocardiogram or echocardiography. The mother’s screening for autoimmune disease was normal. Four maternal uncles had unexplained deaths at the ages of four, nine, thirty and forty years. The other uncles and aunts could not be screened (Figure 3).
To summarize, out of seven siblings, four had cardiac conduction defects with multiple bony exostoses and two of them also had conductive deafness. Two of the remaining three siblings had only multiple bony exostoses.
Heart block, which is discovered in early childhood, in the absence of any known cause, is usually regarded as congenital.Morquio in 1901, had described a family in which several siblings had bradycardia, syncope and died in childhood and proposed that complete heart block could be congenital and familial9. Congenital complete heart block may not present itself until the child is a few years old. The mean age of patients with complete heart block at presentation to The Hospital for Sick Children, Toronto, was 4.9 years9. The mean age at presentation in this family was 11.5 years. Four of seven (57%) had conduction defects with normal cardiac structure and function and six (85%) had multiple bony exostoses. Complete heart block in childhood is either congenital or acquired. Congenital complete heart block not associated with a structural heart disease may be familial in association with cardiomyopathy or systemic lupus erythematosus1,2,5,10. Familial heart block of a progressive nature is an autosomal dominant disorder presenting at variable ages11. The presence of a left anterior hemiblock associated with a right bundle branch block and a prolonged P-R interval (trifasicular block) onthe electrocardiogram may provide a clue to patients at risk of progressing to a complete heart block12. The progressive nature of the cardiac conduction disorder was seen in case number 3 in our series in whom the cardiac rhythm deteriorated and he developed, in addition to his previous dysrhythmia, aprolongedP-Rinterval and atrial extra systoles.
The exact pathogenesis of progressive conduction defect is not known. Cardiac conduction tissue develops in response to a genetic control different from that forming the rest of the heart. Anderson et al have hypothesized that a pnmaiy malformation of the conduction tissue, whereby after its formation it becomes interrupted by fibrosis, is responsible forthe heart block13. Lev and his colleagues, in their extensive work, have sub-divided complete heart block in “normal” hearts into cases with discontinuity between atria and the node and those with discontinuity between the node and the ventricular conducting tissue. They proposed that the disrupted conducting tissue becomes replaced by spaces containing strands of collagenous and elastic tissue thereby producing a progressive conduction block14,15. There have been no reports on any bone abnormalities occurring in association with cardiac conduction defects. Multiple exostoses are benign bone tumors, inherited as an autosomal dominant trait. They are rarely detectable even radiologically before three years of age16. Symptoms develop when the exostoses are large enough to compress neurovascular bundles or obstruct the external auditoiy meatus causing conductive hearing loss. This was the cause of conductive deafness in two siblings in our series (Table I).
Since cardiac conduction defects were present in four siblings and multiple exostoses in six, it seems likely that cardiac conduction abnormality is genetically transmitted and the gene responsible is probably in close proximity to the one causing multiple exostoses or this may be an association by chance. Apart from the possibility of genetic transmission, congenital cardiac conduction defects could represent a developmental error encountered in the early embryological period13, the progressive nature manifesting in childhood. Follow-up of the two children who have multiple exostoses but no dysrhythmia would throw more light on the issue. In conclusion, serious conduction defects are present in a significant number of siblings of this family with structurally nonnal hearts. The association of exostoses raises interesting possibilities of gene location and transmission.
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