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EKG abnormalities in pediatric patients with myotonic dystrophy
EKG Abnormalities in Pediatric Patients with Myotonic Dystrophy J o e l C. M o r g e n l a n d e r , M D * , V i r i n d e r N o h r i a , MD+, a n d Ziad Saba, MD*
Electrocardiographic (EKG) abnormalities are frequent in patients with myotonic dystrophy; cardiac complications may lead to significant morbidity and mortality. The charts of 17 pediatric patients with myotonic dystrophy were reviewed to ascertain the frequency of EKG abnormalities and cardiovascular symptoms. Fifteen of 17 patients had abnormal EKGs with sinus bradycardia being the most common abnormality. Only 1 of 17 patients had cardiovascular symptoms. Four patients had moderate to severe weakness and 3 of them had a conduction disturbance (i.e., first-degree AV block or intraventricular conduction delay). Two of the remaining 13 patients with mild weakness had conduction disturbances. No pediatric patients had progressive EKG abnormalities during follow-up. Baseline EKG study of pediatric patients with myotonic dystrophy is recommended because abnormalities are frequent and usually asymptomatic. Frequent follow-up EKGs are probably unnecessary unless the patient is symptomatic or has heart block. Morgenlander JC, Nohria V, Saba Z. EKG abnormalities in pediatric patients with myotonic dystrophy. Pediatr Neurol 1993;9:124-6.
Introduction Myotonic dystrophy is an autosomal dominant, multisystem disease linked to chromosome 19 [1]. Recent studies demonstrated a trinucleotide repeat sequence that is expanded and which codes for a protein kinase [2]. Cardiac dysfunction is an important cause of morbidity and mortality in adults [3]. Electrocardiographic (EKG) abnormalities are common in adults and are observed more frequently in those with clinically severe neuromuscular disease [4,5]. Because EKG abnormalities include heart block that can be slowly progressive, screening EKGs at frequent intervals have been recommended [6]. Conduction abnormalities have also been demonstrated to be progressive by serial etectrophysiologic study [3,7]. The frequency of EKG abnormalities in the pediatric popula-
From the *Departmentof Medicine,Divisionof Neurology; Department of Pediatrics, Divisionsof *Pediatric Neurology and *Cardiology;Duke UniversityMedical Center; Durham, North Carolina.
124 PEDIATRIC NEUROLOGY Vol.9 No. 2
tion is less clear. Forsberg et al. reported 7 patients with congenital myotonic dystrophy of mean age 19 and found 6 to have abnormal EKGs [8]. Cardiovascular symptoms were not reported. Our study was performed to evaluate the frequency of EKG abnormalities in a pediatric population with myotonic dystrophy and to correlate these abnormalities with symptoms in order to determine whether screening EKGs should be performed in all pediatric patients with myotonic dystrophy or only in those who are symptomatic and to determine at what intervals they should be repeated.
Methods We reviewed the charts of all patients diagno~d with myotonic dystrophy at the Duke UniversityMuscularDystrophy Clinic [or the last 20 years. Diagnosiswas made by a neurologistutilizingpatient history, family history, physical examination,ocular examination,and electromyography as needed. Eighteen patients were 18 years of"age or younger at diagnosisand 17 had at least 1 EKG prior to age 19. Patientswere asked at each visit about chest pain, palpitations, shortness of breath, and syncope. Parents were asked about their children's exercise and feeding tolerance. EKGs were interpretedby a pediatric cardiologyfellow using standard criteria [9]. Age at diagnosis, maternal or paternal inheritance, and ancillary cardiovascular studies (i.e., Hoher monitor, echocardiogram) were recorded. Neuromuscular weakness was classified as mild if only distal muscles were minimally affected without functionallimitation,moderate if there was functionallimitationbut the patient was independentfor activities of daily living, and severe if the patient was functionallylimited and dependent for activities of daily living. Years of follow-upwere recorded. No patients received procainamide or quininetherapy for myotonia.
Results Seventeen patients were studied and 15 (88%) had EKG abnormalities (Table 1). The most common abnormality was sinus bradycardia, observed in 11 patients. The lowest heart rates were 42, 44, and 49 in Patients 4, 9, and 17, respectively. All other patients had heart rates of at least 50. Three patients had right axis deviation and 3 had first-degree AV block. Two patients had intraventricular conduction delay and 2 had left axis deviation. One each had right ventricular hypertrophy and premature ventricular contractions. Age at diagnosis did not correlate with the presence of conduction disturbance. Three
Communicationsshould be addressed to: Dr. Morgenlander;Box 3394; Duke UniversityMedical Center; Durham, NC 27710. Received October 20, 1992; accepted January 13, 1993.
Table 1. Data on pediatric patients with myotoulc dystrophy
Pt. No.
Age at Diagnosis (yrs)
Severity of Disease
Inheritance
EKG Abnormalities
Ancillary Cardiac Studies
Years of Follow-up (up to age 18)
Cardiovascular Symptoms
1
C
Mod
Maternal
1° AVB
--
3
None
2
C
Severe
Maternal
RAD, RVH
--
5
None
3
4
Mild
Paternal
None
--
4
None
4
6
Mild
Maternal
SB
Holter-SB, brief sinus pauses; echo normal
8
None
5
6
Mod
Patemal
SB, IVCD
--
1
None
6
7
Mild
Maternal
LAD, PVC
Holter-PVC
3
None
7
7
Mod
Maternal
SB, RAD, l ° AVB
Holter-SB, 1o AVB; echo-MVP
9
Palpitations
8
8
Mild
Paternal
None
--
8
None
9
11
Mild
Maternal
SB, LAD
--
6
None
10
11
Mild
Maternal
SB
--
< 1
None
11
11
Mild
Matemal
SB
--
2
None
12
13
Mild
Maternal
SB
--
2
None
13
13
Mild
Paternal
1° AVB
--
1
None
14
13
Mild
Maternal
SB, IVCD
--
2
None
15
14
Mild
Maternal
SB, RAD
1
None
16
15
Mild
Maternal
SB
--
1
None
17
18
Mild
Paternal
SB
--
1
None
Abbreviations: 1° AVB = First-degree heart block C = Congenital IVCD = Intraventricular conduction delay LAD = Left axis deviation
MVP PVC RAD SB
= = = =
Ecbo-MVP
Mitral valve prolapse Premature ventricular contraction Right axis deviation Sinus bradycardia
o f 4 p a t i e n t s w i t h m o d e r a t e or s e v e r e n e u r o m u s c u l a r dysf u n c t i o n h a d c o n d u c t i o n a b n o r m a l i t i e s (i.e., f i r s t - d e g r e e A V b l o c k or i n t r a v e n t r i c u l a r c o n d u c t i o n delay), w h i l e 2 o f 13 p a t i e n t s w i t h m i l d d i s e a s e h a d c o n d u c t i o n d i s t u r b a n c e . M a t e r n a l i n h e r i t a n c e o c c u r r e d i n 12 o f 17 p a t i e n t s ; 3 patients w i t h m a t e r n a l i n h e r i t a n c e a n d 2 p a t i e n t s w i t h p a t e r nal i n h e r i t a n c e h a d c o n d u c t i o n d i s t u r b a n c e s . T h e 2 patients w i t h n o r m a l E K G s h a d p a t e r n a l i n h e r i t a n c e . Progressive conduction block was not observed in our patients. A v e r a g e d u r a t i o n o f f o l l o w - u p u n t i l a g e 19 was 3.4 years. P a t i e n t s 3, 5, a n d 13 w e r e f o l l o w e d b e y o n d t h e a g e o f 18 f o r 10, 15, a n d 17 years, respectively. N o signif i c a n t c h a n g e s in t h e i r E K G s w e r e o b s e r v e d d u r i n g this p e r i o d o f f o l l o w - u p . P a t i e n t 7 w a s the o n l y o n e w h o c o m p l a i n e d o f c a r d i o v a s c u l a r s y m p t o m s a n d t h o s e w e r e palp i t a t i o n s w i t h exercise. S h e h a d s i n u s b r a d y c a r d i a , r i g h t axis d e v i a t i o n , a n d f i r s t - d e g r e e AV b l o c k o n E K G . T h e s e
findings were confirmed by 24-hour Holter monitoring; echocardiogram revealed mitral valve prolapse. Mitral v a l v e p r o l a p s e was also o b s e r v e d i n 1 a s y m p t o m a t i c patient who received a cardiac work-up because of a murm u r h e a r d o n c a r d i a c e x a m i n a t i o n . P a t i e n t 4 r e c e i v e d anciliary c a r d i a c studies b e c a u s e o f a n i r r e g u l a r h e a r t rate and Patient 6 had Holter monitoring because of extrasystoles o n E K G . N o o t h e r s i g n i f i c a n t a b n o r m a l i t i e s w e r e f o u n d in t h e s e patients. Discussion Adults with myotonic dystrophy have frequent EKG a n d e l e c t r o p h y s i o l o g i c a b n o r m a l i t i e s . S u d d e n d e a t h occurs in adult a n d p e d i a t r i c p a t i e n t s e i t h e r b e c a u s e o f arr h y t h m i a s or p r o g r e s s i v e h e a r t b l o c k [10]. P a t i e n t s c a n b e a s y m p t o m a t i c p r i o r to s u d d e n d e a t h [3,10]. P a t i e n t s w i t h tachyarrhythmias may benefit from electrophysiologic
Morgenlander et al: EKG and Myotonic Dystrophy
125
study and medical therapy while patients with symptomatic bradycardia or progressive heart block may benefit from pacemaker insertion [6,7]. Pathologic studies of cardiac tissue in adults and pediatric patients with myotonic dystrophy demonstrate fibrosis, fatty infiltration, and atrophy of the conduction system along with myofibrillar degeneration by electron microscopy [10,11 ]. Severity of the E K G conduction abnormalities correlate with the severity of pathologic findings [ 11 ]. This chart review documented that EKG abnormalities are frequent in pediatric patients with myotonic dystrophy and that the abnormalities are usually asymptomatic. For most of our patients, the follow-up period was too short to confirm that progressive conduction disturbances did not occur; however, we found no evidence of progressive abnormalities in our pediatric patients. Four of our patients had moderate or severe disability due to neuromuscular symptoms and all of those patients had EKG abnormalities with 3 of 4 having conduction disturbances. Three of those 4 patients had maternal inheritance. We recommend baseline screening EKGs in pediatric patients diagnosed with myotonic dystrophy because E K G abnormalities are frequent and usually asymptomatte. Because of our small cohort we cannot be sure that progressive heart block does not occur and periodic EKG recordings are suggested when conduction abnormalities are present. Although our study was small and retrospective, there was no evidence of significant, progressive EKG abnormalities; therefore, yearly EKG recordings are probably not needed. Fatigue in these patients may be partially attributed to sinus bradycardia when present. Symptomatic patients should have cardiology consultation along with prolonged E K G monitoring as needed. Electrophysiologic study may be useful in evaluating patients with brady- or tachyarrhythmias. Procainamide and quinine are sometimes used to treat symptomatic myotonia but must be used with caution because these drugs may cause PR interval prolongation [12]. Further follow-up studies are needed to determine whether abnor-
126 PEDIATRIC NEUROLOGY Vol.9 No. 2
realities in childhood predict eventual cardiac sylnptom~ in adulthood.
We acknowledge tile Muscular l)ystrophy Associali.n lk~t their continued support of the Duke Muscular Dystrophy ('linic. (;inger Tttck was of great assistance in obtaining the patient charts Wanda Beam is thanked for her secretarial support.
References
[1] Brunner HG, Smeets H, LambermonHMM, et at. A nmltipoint linkage map around the locus for myotonicdystrophy on chromosome 19. Genomics 1989;5:589-95. [2] Brook JD, McCurrach ME, Harley HG, et al. Molecularbasis of myotonic dystrophy: Expansionof a trinculeotide(CTG) repeat at the 3' end of a transcriptencodinga protein kinase family member.Cell 1992; 68:799-808. [3] Moorman JR, ColemanRE, Packer DL, et at. Cardiac involvement in myotonicmusculardystrophy. Medicine 1985;64:371-87. [4] Church SC. The heart in myotoniaatrophica. Arch Intern Med 1967;119:176-81. [5] Olofsson BO, Forsberg H, AnderssonS, Bjerle P, HenrikssonA, Wedin I. Electrocardiographicfindingsin myotonicdystrophy. Br Heart J 1988;59:47-52. [6] HawleyILl, MilnerMR, GondienerJS, Cohen A. Myotonicheart disease: A clinical follow-up.Neurology 1991;41:259-62. [7] Prystowsky EN, Pritchett ELC, Roses AD, Gallagher J. The natural history of conductionsystem disease in myotonicmusculardystrophy as determined by serial electrophysiologic studies. Circulation 1979;60:1360-4. [8] Forsberg H, Olofsson BO, Eriksson A, Andersson S. Cardiac involvement in congenital myotonic dystrophy. Br Heart J 1990;63: 119-21.
[9] Garson A. Electrocardiography. In: Garson A, Bricker JT, McNamara DG, eds. The science and practice of pediatric cardiology, vol II. Philadelphia:Lea Febiger, 1990;713-4. [10] NguyenHH, Wolfe JT, Holmes DR, Edwards WD. Pathology of the cardiac conductionsystem in myotonicdystrophy: A study of 12 cases. J Am Coil Cardiol 1988;11:662-71. [11] Motta G, GuilleminaultC, Bil!inghamM, Barry W, Mason J. Cardiac abnormalitiesin myotonic dystrophy: Electrophysiologicand histopathologic studies. Am J Med 1979;67:467-73. [12] Griggs RC, Davis ILl, AndersonDC, Dove JT. Cardiac conduction in myotonicdystrophy.Am J Med 1975;59:37-42.
Electrocardiographic (EKG) abnormalities are frequent in patients with myotonic dystrophy; cardiac complications may lead to significant morbidity and mortality. The charts of 17 pediatric patients with myotonic dystrophy were reviewed to ascertain the frequency of EKG abnormalities and cardiovascular symptoms. Fifteen of 17 patients had abnormal EKGs with sinus bradycardia being the most common abnormality. Only 1 of 17 patients had cardiovascular symptoms. Four patients had moderate to severe weakness and 3 of them had a conduction disturbance (i.e., first-degree AV block or intraventricular conduction delay). Two of the remaining 13 patients with mild weakness had conduction disturbances. No pediatric patients had progressive EKG abnormalities during follow-up. Baseline EKG study of pediatric patients with myotonic dystrophy is recommended because abnormalities are frequent and usually asymptomatic. Frequent follow-up EKGs are probably unnecessary unless the patient is symptomatic or has heart block. Morgenlander JC, Nohria V, Saba Z. EKG abnormalities in pediatric patients with myotonic dystrophy. Pediatr Neurol 1993;9:124-6.
Introduction Myotonic dystrophy is an autosomal dominant, multisystem disease linked to chromosome 19 [1]. Recent studies demonstrated a trinucleotide repeat sequence that is expanded and which codes for a protein kinase [2]. Cardiac dysfunction is an important cause of morbidity and mortality in adults [3]. Electrocardiographic (EKG) abnormalities are common in adults and are observed more frequently in those with clinically severe neuromuscular disease [4,5]. Because EKG abnormalities include heart block that can be slowly progressive, screening EKGs at frequent intervals have been recommended [6]. Conduction abnormalities have also been demonstrated to be progressive by serial etectrophysiologic study [3,7]. The frequency of EKG abnormalities in the pediatric popula-
From the *Departmentof Medicine,Divisionof Neurology; Department of Pediatrics, Divisionsof *Pediatric Neurology and *Cardiology;Duke UniversityMedical Center; Durham, North Carolina.
124 PEDIATRIC NEUROLOGY Vol.9 No. 2
tion is less clear. Forsberg et al. reported 7 patients with congenital myotonic dystrophy of mean age 19 and found 6 to have abnormal EKGs [8]. Cardiovascular symptoms were not reported. Our study was performed to evaluate the frequency of EKG abnormalities in a pediatric population with myotonic dystrophy and to correlate these abnormalities with symptoms in order to determine whether screening EKGs should be performed in all pediatric patients with myotonic dystrophy or only in those who are symptomatic and to determine at what intervals they should be repeated.
Methods We reviewed the charts of all patients diagno~d with myotonic dystrophy at the Duke UniversityMuscularDystrophy Clinic [or the last 20 years. Diagnosiswas made by a neurologistutilizingpatient history, family history, physical examination,ocular examination,and electromyography as needed. Eighteen patients were 18 years of"age or younger at diagnosisand 17 had at least 1 EKG prior to age 19. Patientswere asked at each visit about chest pain, palpitations, shortness of breath, and syncope. Parents were asked about their children's exercise and feeding tolerance. EKGs were interpretedby a pediatric cardiologyfellow using standard criteria [9]. Age at diagnosis, maternal or paternal inheritance, and ancillary cardiovascular studies (i.e., Hoher monitor, echocardiogram) were recorded. Neuromuscular weakness was classified as mild if only distal muscles were minimally affected without functionallimitation,moderate if there was functionallimitationbut the patient was independentfor activities of daily living, and severe if the patient was functionallylimited and dependent for activities of daily living. Years of follow-upwere recorded. No patients received procainamide or quininetherapy for myotonia.
Results Seventeen patients were studied and 15 (88%) had EKG abnormalities (Table 1). The most common abnormality was sinus bradycardia, observed in 11 patients. The lowest heart rates were 42, 44, and 49 in Patients 4, 9, and 17, respectively. All other patients had heart rates of at least 50. Three patients had right axis deviation and 3 had first-degree AV block. Two patients had intraventricular conduction delay and 2 had left axis deviation. One each had right ventricular hypertrophy and premature ventricular contractions. Age at diagnosis did not correlate with the presence of conduction disturbance. Three
Communicationsshould be addressed to: Dr. Morgenlander;Box 3394; Duke UniversityMedical Center; Durham, NC 27710. Received October 20, 1992; accepted January 13, 1993.
Table 1. Data on pediatric patients with myotoulc dystrophy
Pt. No.
Age at Diagnosis (yrs)
Severity of Disease
Inheritance
EKG Abnormalities
Ancillary Cardiac Studies
Years of Follow-up (up to age 18)
Cardiovascular Symptoms
1
C
Mod
Maternal
1° AVB
--
3
None
2
C
Severe
Maternal
RAD, RVH
--
5
None
3
4
Mild
Paternal
None
--
4
None
4
6
Mild
Maternal
SB
Holter-SB, brief sinus pauses; echo normal
8
None
5
6
Mod
Patemal
SB, IVCD
--
1
None
6
7
Mild
Maternal
LAD, PVC
Holter-PVC
3
None
7
7
Mod
Maternal
SB, RAD, l ° AVB
Holter-SB, 1o AVB; echo-MVP
9
Palpitations
8
8
Mild
Paternal
None
--
8
None
9
11
Mild
Maternal
SB, LAD
--
6
None
10
11
Mild
Maternal
SB
--
< 1
None
11
11
Mild
Matemal
SB
--
2
None
12
13
Mild
Maternal
SB
--
2
None
13
13
Mild
Paternal
1° AVB
--
1
None
14
13
Mild
Maternal
SB, IVCD
--
2
None
15
14
Mild
Maternal
SB, RAD
1
None
16
15
Mild
Maternal
SB
--
1
None
17
18
Mild
Paternal
SB
--
1
None
Abbreviations: 1° AVB = First-degree heart block C = Congenital IVCD = Intraventricular conduction delay LAD = Left axis deviation
MVP PVC RAD SB
= = = =
Ecbo-MVP
Mitral valve prolapse Premature ventricular contraction Right axis deviation Sinus bradycardia
o f 4 p a t i e n t s w i t h m o d e r a t e or s e v e r e n e u r o m u s c u l a r dysf u n c t i o n h a d c o n d u c t i o n a b n o r m a l i t i e s (i.e., f i r s t - d e g r e e A V b l o c k or i n t r a v e n t r i c u l a r c o n d u c t i o n delay), w h i l e 2 o f 13 p a t i e n t s w i t h m i l d d i s e a s e h a d c o n d u c t i o n d i s t u r b a n c e . M a t e r n a l i n h e r i t a n c e o c c u r r e d i n 12 o f 17 p a t i e n t s ; 3 patients w i t h m a t e r n a l i n h e r i t a n c e a n d 2 p a t i e n t s w i t h p a t e r nal i n h e r i t a n c e h a d c o n d u c t i o n d i s t u r b a n c e s . T h e 2 patients w i t h n o r m a l E K G s h a d p a t e r n a l i n h e r i t a n c e . Progressive conduction block was not observed in our patients. A v e r a g e d u r a t i o n o f f o l l o w - u p u n t i l a g e 19 was 3.4 years. P a t i e n t s 3, 5, a n d 13 w e r e f o l l o w e d b e y o n d t h e a g e o f 18 f o r 10, 15, a n d 17 years, respectively. N o signif i c a n t c h a n g e s in t h e i r E K G s w e r e o b s e r v e d d u r i n g this p e r i o d o f f o l l o w - u p . P a t i e n t 7 w a s the o n l y o n e w h o c o m p l a i n e d o f c a r d i o v a s c u l a r s y m p t o m s a n d t h o s e w e r e palp i t a t i o n s w i t h exercise. S h e h a d s i n u s b r a d y c a r d i a , r i g h t axis d e v i a t i o n , a n d f i r s t - d e g r e e AV b l o c k o n E K G . T h e s e
findings were confirmed by 24-hour Holter monitoring; echocardiogram revealed mitral valve prolapse. Mitral v a l v e p r o l a p s e was also o b s e r v e d i n 1 a s y m p t o m a t i c patient who received a cardiac work-up because of a murm u r h e a r d o n c a r d i a c e x a m i n a t i o n . P a t i e n t 4 r e c e i v e d anciliary c a r d i a c studies b e c a u s e o f a n i r r e g u l a r h e a r t rate and Patient 6 had Holter monitoring because of extrasystoles o n E K G . N o o t h e r s i g n i f i c a n t a b n o r m a l i t i e s w e r e f o u n d in t h e s e patients. Discussion Adults with myotonic dystrophy have frequent EKG a n d e l e c t r o p h y s i o l o g i c a b n o r m a l i t i e s . S u d d e n d e a t h occurs in adult a n d p e d i a t r i c p a t i e n t s e i t h e r b e c a u s e o f arr h y t h m i a s or p r o g r e s s i v e h e a r t b l o c k [10]. P a t i e n t s c a n b e a s y m p t o m a t i c p r i o r to s u d d e n d e a t h [3,10]. P a t i e n t s w i t h tachyarrhythmias may benefit from electrophysiologic
Morgenlander et al: EKG and Myotonic Dystrophy
125
study and medical therapy while patients with symptomatic bradycardia or progressive heart block may benefit from pacemaker insertion [6,7]. Pathologic studies of cardiac tissue in adults and pediatric patients with myotonic dystrophy demonstrate fibrosis, fatty infiltration, and atrophy of the conduction system along with myofibrillar degeneration by electron microscopy [10,11 ]. Severity of the E K G conduction abnormalities correlate with the severity of pathologic findings [ 11 ]. This chart review documented that EKG abnormalities are frequent in pediatric patients with myotonic dystrophy and that the abnormalities are usually asymptomatic. For most of our patients, the follow-up period was too short to confirm that progressive conduction disturbances did not occur; however, we found no evidence of progressive abnormalities in our pediatric patients. Four of our patients had moderate or severe disability due to neuromuscular symptoms and all of those patients had EKG abnormalities with 3 of 4 having conduction disturbances. Three of those 4 patients had maternal inheritance. We recommend baseline screening EKGs in pediatric patients diagnosed with myotonic dystrophy because E K G abnormalities are frequent and usually asymptomatte. Because of our small cohort we cannot be sure that progressive heart block does not occur and periodic EKG recordings are suggested when conduction abnormalities are present. Although our study was small and retrospective, there was no evidence of significant, progressive EKG abnormalities; therefore, yearly EKG recordings are probably not needed. Fatigue in these patients may be partially attributed to sinus bradycardia when present. Symptomatic patients should have cardiology consultation along with prolonged E K G monitoring as needed. Electrophysiologic study may be useful in evaluating patients with brady- or tachyarrhythmias. Procainamide and quinine are sometimes used to treat symptomatic myotonia but must be used with caution because these drugs may cause PR interval prolongation [12]. Further follow-up studies are needed to determine whether abnor-
126 PEDIATRIC NEUROLOGY Vol.9 No. 2
realities in childhood predict eventual cardiac sylnptom~ in adulthood.
We acknowledge tile Muscular l)ystrophy Associali.n lk~t their continued support of the Duke Muscular Dystrophy ('linic. (;inger Tttck was of great assistance in obtaining the patient charts Wanda Beam is thanked for her secretarial support.
References
[1] Brunner HG, Smeets H, LambermonHMM, et at. A nmltipoint linkage map around the locus for myotonicdystrophy on chromosome 19. Genomics 1989;5:589-95. [2] Brook JD, McCurrach ME, Harley HG, et al. Molecularbasis of myotonic dystrophy: Expansionof a trinculeotide(CTG) repeat at the 3' end of a transcriptencodinga protein kinase family member.Cell 1992; 68:799-808. [3] Moorman JR, ColemanRE, Packer DL, et at. Cardiac involvement in myotonicmusculardystrophy. Medicine 1985;64:371-87. [4] Church SC. The heart in myotoniaatrophica. Arch Intern Med 1967;119:176-81. [5] Olofsson BO, Forsberg H, AnderssonS, Bjerle P, HenrikssonA, Wedin I. Electrocardiographicfindingsin myotonicdystrophy. Br Heart J 1988;59:47-52. [6] HawleyILl, MilnerMR, GondienerJS, Cohen A. Myotonicheart disease: A clinical follow-up.Neurology 1991;41:259-62. [7] Prystowsky EN, Pritchett ELC, Roses AD, Gallagher J. The natural history of conductionsystem disease in myotonicmusculardystrophy as determined by serial electrophysiologic studies. Circulation 1979;60:1360-4. [8] Forsberg H, Olofsson BO, Eriksson A, Andersson S. Cardiac involvement in congenital myotonic dystrophy. Br Heart J 1990;63: 119-21.
[9] Garson A. Electrocardiography. In: Garson A, Bricker JT, McNamara DG, eds. The science and practice of pediatric cardiology, vol II. Philadelphia:Lea Febiger, 1990;713-4. [10] NguyenHH, Wolfe JT, Holmes DR, Edwards WD. Pathology of the cardiac conductionsystem in myotonicdystrophy: A study of 12 cases. J Am Coil Cardiol 1988;11:662-71. [11] Motta G, GuilleminaultC, Bil!inghamM, Barry W, Mason J. Cardiac abnormalitiesin myotonic dystrophy: Electrophysiologicand histopathologic studies. Am J Med 1979;67:467-73. [12] Griggs RC, Davis ILl, AndersonDC, Dove JT. Cardiac conduction in myotonicdystrophy.Am J Med 1975;59:37-42.