Juvenile Colonic Polyposis Associated with Congenital Heart Disease* L. ONA~N, M.D., B. ~AHiN, M.D., G. TEMVgiN, M.D., A. GOKOZ, M.D.
JUVENILE COLONIC POLYPOSIS has recently been described as a d i f f e r e n t entity f r o m o t h e r j u v e n i l e f o r m s o f polyposis? -5 Juvenile colonic polyposis is hereditary. Its genetic p r o p e r t i e s are not well known. ~ T h e pedigrees o f some families suggest that the p r e s e n c e o f allelic genes p r o b a b l y leads to the d e v e l o p m e n t o f a d e n o m a t o u s a n d juvenile polyps in d i f f e r e n t m e m bers o f these families, 2-4,s but this hypothesis has not yet been c o n f i r m e d .
Material and Methods In this report, the cases o f f o u r patients f r o m a family with juvenile colonic polyposis, showing direct transmission to children f r o m the fathers, in two gen* Received for publication May 11, 1978. Address reprint requests to Dr. ~ahin: Ydksek ihtisas Hastahanesi (Subspecialty Training Hospital), Ankara, Turkey.
Unexlmined
,-,.0
ffnexanincd h i a t o r y of diecharge of polyps
J.C.P.
@
From Yuksek ]htisas Hastahanesi (the Subspecialty Training Hospital Center), Ankara, Turkey erations, are presented. F u r t h e r m o r e , all these patients also had atrial septal defects a n d p u l m o n a r y stenosis (Fig. 1). Cardiologic e x a m i n a t i o n s o f the patients and surgical interventions were p e r f o r m e d at the Cardiology a n d Cardiovascular Clinics o f the Ydksek ihtisas Hastahanesi (Subspecialty T r a i n i n g Hospital Center) o f Ankara, T u r k e y .
Report of Four Cases Patient 1. A 9-year-old girl had had abdominal pain, diarrhea, rectal bleeding, and prolapse of the anus since infancy. Generalized pallor, clubbing of fingers, and a grade 2/6 systolicejection murmur audible over the s~cond left intercostal space were found on physical examination. Proetosigmoidoscopy revealed many pedunculated
(2)
Congenital heart disease
0
|
9 K,S, (30)
K,A, (9)
K,K. (6)
K.$, (4) FIG. i.
(2)
(3 MONTH)
Pedigree of the family.
0012-3706/78/1000/0501/$00.75 9 American Society of Colon and Rectal Surgeons
501
K.O, (50)
502
ONAIC4.N, ET AL.
Dis. Coi.&1978 Rec. October
Patient 2. A 6-year-old girl was the sister of Patient I. Her main complaints were rectal bleeding and rectal prolapse. Generalized pallor, clubbing of fingers, and a grade 2/6 systolic ejection m u r m u r audible over the second left intercostal space were found on physical examination. Many pedunculated polyps, ranging in size from a few millimeters to 1-2 cm, were seen upon proctosigmoidoscopic examination. Malay polyps were seen on barium-enema examination. Teleroentge nogram o fthe chest showed cardiomegaly, particularly right atrial enlargement (Fig. 7), but the EKG was normal (Fig. 8). An atrial septal defect and pulmonary stenosis were found as a result of hemodynamic examinations. Operation confirmed a septum secundum type o fatrial septal defect and valvular pulmonary stenosis. The diagnosis was juvenile polyposis of the colon with atrial septal defect and pulmonary valvular stenosis. Patient 3. A 4-year-old boy, the brother of Patients l and 2, corn plained of rectal bleeding and anal prolapse. Generalized pallor, clubbing of fingers, a systolic thrill, and a grade 3/6 systolic ejection m u r m u r in the pulmonary area were found on physical examination. Many" pedunculated polyps ranging in size from a few millimeters to 1-2 cm were seen on proctosigmoidoscopy. Cardiomegaly and right ventricular hypertrophy were evidenced by radiography and the EKG (Figs. 9 and 10). Hemodynamic findings indicated an atrial septal defect, p u l m o n a r y v a l v u l a r stenosis, and a n o m a l o u s puhnonary drainage (presumably between the puhnonary vein and superior vena cava). The diagnosis wasjuvenile polyposis of the colon, with atrial septal defect, pulmonary vaI~ ular stenosis, and abnormal venous drainage.
FIO. 2.
Rectosigmoidoscopic appearance of polyps, Patient l.
polyps ranging in size from a few millimeters to 1-2 cm (Fig. 2). Large cysts filled with abundant mucin, typical of juvenile polyps, were disclosed by histologic examination (Fig. 3). Polyps with many filling defects were observed on radiologic examination of the colon (Fig. 4). Teleroentgenogram of the chest was normal (Fig. 5). T h e EKG showed left axis deviation (Fig. 6). Hemodynamic examinations could not be completed. Consequently, a diagnosis of juvenile colonic polyposis, pulmonary stenosis, and suspected atrial septal defect was made.
Patient 4. A 30-year-old man was the father of the first three patients. He had complained of rectal bleeding and discharge of polyps since childhood. Generalized pallor, clubbing of fingers, and a grade 2/6 systolic ejection m u r m u r over the second left intercostal space were again found on physical examination. Likewise, many pedunculated polyps, ranging in size from a few millimeters to 1-2 cm, were seen on proctosigmoidoscopy. T h e histologic diagnosis was juvenile polyps. Barium-enema study also demonstrated many polyps. Teleroentgenogram was normal (Fig. 11). T h e EKG showed right axis deviation a n d incomplete right bundle-branch block (Fig. 12). T h e diagnosis was atrial septal defect and pulmonary stenosis. It was learned that the father of Patient 4 and the grandfather of Patients 1, 2 and 3, who was 50 years old, also had complaints of
FIG. 3. Histopathologic appearance of a polyp from Patient 1.
Volume 2i Number 7
P O L Y P O S I S A N D H E A R T DISEASE
503
rectal bleeding and discharge of polyps. However, despite all attempts, he could not be examined. The genetic aspect of the family was examined at the Department of Genetics, the Faculty of Medicine of the Hacettepe University, Ankara, and no chromosomal anomaly was found.
FIG. 4. Barium-enema study of Patient 1. Polyps are visible as numerous filling defects.
Fro. 6. EKG of Patient l, showing left axis deviation.
Discussion
Fm. 5.
Teleroentgenogram of Patient 1. Normal.
J u v e n i l e colonic polyposis has b e e n d e s c r i b e d as a s e p a r a t e entity by M o r s o n et al. 4's In a classification devised by Sachatello a n d G r i f f e n , ~ it is n o t e d that the g e n e t i c aspect o f j u v e n i l e colonic p o l y p o s i s is n o t clear, a n d that the disease manifests no p e c u l i a r signs o r s y m p t o m s o t h e r t h a n t h o s e a f f e c t i n g the gastrointestinal tract. T h e direct t r a n s m i s s i o n o f the disease f r o m the f a t h e r s to c h i l d r e n in two g e n e r a t i o n s o f the family we e x a m i n e d is associated with a clearly d o m i n a n t p e n e t r a t i n g gene, which a p p e a r s to be n o n - s e x linked in this family. It is n o t possible to e x p l a i n this p h e n o t y p e , o c c u r r i n g in t h e f a t h e r s a n d the two d a u g h t e r s as well as t h e son, in a n y o t h e r way. At the s a m e time, the g e n e c a u s i n g j u v e n i l e colonic polyposis in this family is r e l a t e d to the g e n e that causes c o n g e n -
504
Dis. Col. & Rect,
O N A R A N , E T AL.
FiG. 7. Teleroentgenogram of Patient 2, showing cardiomegaly, particularly right atrial enlargement.
ital h e a r t disease. Likewise, it seems that this second gene is p r o b a b l y d o m i n a n t and p e n e t r a t i n g but not sex-linked. T h e genetics o f congenital h e a r t disease are not fully u n d e r s t o o d . T h e genetic features o f the m o t h e r a n d the e n v i r o n m e n t u n d o u b t e d l y play imp o r t a n t roles, r but factors related to the age a n d n u m b e r o f p r e g n a n c i e s o f the m o t h e r can be ruled out. T h e a f f e c t e d children were the first children o f the y o u n g m o t h e r . F u r t h e r m o r e , congenital h e a r t
October 1978
FIG. 9. Teleroentgenogram of Patient 3, showing cardiomegaly and right ventricular hypertrophy.
Fro. 10. EKG of Patient 3, showing right axis deviation and right ventricular hypertrophy.
disease a n d juvenile colonic polyposis were f o u n d to be associated with each o t h e r in all cases, elucidating the genetics o f b o t h diseases. O n the o t h e r h a n d , the two diseases were f o u n d to affect the patients equally,
V o l u m e 21 Number 7
POLYPOSIS AND HEART DISEASE
505
thus indicating that the responsible genes are very closely r e l a t e d to e a c h o t h e r o r at least f o u n d in t h e same chromosome. I n t h e l i g h t o f t h e s e f i n d i n g s , we b e l i e v e t h a t we m a y h a v e e n c o u n t e r e d a n e w s y n d r o m e . T h e association of congenital heart disease and adenomatous p o l y p o s i s in a f a m i l y has b e e n r e p o r t e d o n l y o n c e : two patients from a family, a son and the father were a f f e c t e d ? I n a d d i t i o n , a v e n t r i c u l a r s e p t a l d e f e c t was p r e s e n t in o n e o f s e v e n cases o f i n f a n t i l e j u v e n i l e coIonic p o l y p o s i s , ~ b u t no case in w h i c h j u v e n i l e c o l o n i c p o l y p o s i s was a s s o c i a t e d w i t h c o n g e n i t a l h e a r t d i s e a s e has b e e n r e p o r t e d p r e v i o u s l y , r
Summary
FIG. 1 1. Teleroentgenogram of Patient 4. Normal.
Four members of a family with juvenile colonic p o l y p o s i s in two g e n e r a t i o n s w e r e e x a m i n e d by t h e authors. The disease showed a very marked dominant m o d e o f i n h e r i t a n c e , n o t s e x - l i n k e d , in this f a m i l y . A t the same time, the same members of the family had congenital heart disease, including atrial septal defects a n d p u l m o n a r y stenosis. T h i s d i s e a s e also r e suited from a dominant, highly penetrating gene, not sex-linked. The occurrence of both these hereditary d i s e a s e s at t h e s a m e t i m e s u g g e s t s a close r e l a t i o n ship o r link b e t w e e n the r e s p o n s i b l e genes. T h i s c o m bination may represent the emergence of a new syndrome.
References
FIo. 12. EKG of Patient 4, showing right axis deviation and incomplete right bundle-branch block.
I. Aim T, Licznerski G: The intestinal polyposes. Clin Gastroenterol 2:577 (Sept), 1973 2. Bussey HJ: Progress report: Gastrointestinal polyposis. Gut 11: 970, 1970 3. Gathright JR Jr, Cofer TW Jr: Familial incidence of juvenile polyposis coll. Surg Gynecol Obstet 138: 185, 1974 4. McColl I, Bussey HJ, Veale AM, et al: Juvenile polyposis coli. Proc R Soc Med 57: 896, 1964 5. Sachatetlo CR, Griffen WOJr: Hereditary polypoid diseases of the gastrointestinal tract: A working classification. Am J Surg 129: 198, 1975 6. Sachatello, CR, Hahn IS, Carrington CB: Juvenile gastrointestinal polyposis in a female infant: Report of a case and review of the literature of a recently recognized syndrome. Surgery 75: 107, 1974 7. Taylor wJ: Genetics and Cardiovascular System. In HurstJW: The Heart; Arteries and Veins. Ed 3, New York, McGrawHill Book Company, 1974, p 606 8. Veale AM, McCotl t, Bussey HJ, et al: Juvenile potyposis coil J Med Genet 3: 5, 1966
JUVENILE COLONIC POLYPOSIS has recently been described as a d i f f e r e n t entity f r o m o t h e r j u v e n i l e f o r m s o f polyposis? -5 Juvenile colonic polyposis is hereditary. Its genetic p r o p e r t i e s are not well known. ~ T h e pedigrees o f some families suggest that the p r e s e n c e o f allelic genes p r o b a b l y leads to the d e v e l o p m e n t o f a d e n o m a t o u s a n d juvenile polyps in d i f f e r e n t m e m bers o f these families, 2-4,s but this hypothesis has not yet been c o n f i r m e d .
Material and Methods In this report, the cases o f f o u r patients f r o m a family with juvenile colonic polyposis, showing direct transmission to children f r o m the fathers, in two gen* Received for publication May 11, 1978. Address reprint requests to Dr. ~ahin: Ydksek ihtisas Hastahanesi (Subspecialty Training Hospital), Ankara, Turkey.
Unexlmined
,-,.0
ffnexanincd h i a t o r y of diecharge of polyps
J.C.P.
@
From Yuksek ]htisas Hastahanesi (the Subspecialty Training Hospital Center), Ankara, Turkey erations, are presented. F u r t h e r m o r e , all these patients also had atrial septal defects a n d p u l m o n a r y stenosis (Fig. 1). Cardiologic e x a m i n a t i o n s o f the patients and surgical interventions were p e r f o r m e d at the Cardiology a n d Cardiovascular Clinics o f the Ydksek ihtisas Hastahanesi (Subspecialty T r a i n i n g Hospital Center) o f Ankara, T u r k e y .
Report of Four Cases Patient 1. A 9-year-old girl had had abdominal pain, diarrhea, rectal bleeding, and prolapse of the anus since infancy. Generalized pallor, clubbing of fingers, and a grade 2/6 systolicejection murmur audible over the s~cond left intercostal space were found on physical examination. Proetosigmoidoscopy revealed many pedunculated
(2)
Congenital heart disease
0
|
9 K,S, (30)
K,A, (9)
K,K. (6)
K.$, (4) FIG. i.
(2)
(3 MONTH)
Pedigree of the family.
0012-3706/78/1000/0501/$00.75 9 American Society of Colon and Rectal Surgeons
501
K.O, (50)
502
ONAIC4.N, ET AL.
Dis. Coi.&1978 Rec. October
Patient 2. A 6-year-old girl was the sister of Patient I. Her main complaints were rectal bleeding and rectal prolapse. Generalized pallor, clubbing of fingers, and a grade 2/6 systolic ejection m u r m u r audible over the second left intercostal space were found on physical examination. Many pedunculated polyps, ranging in size from a few millimeters to 1-2 cm, were seen upon proctosigmoidoscopic examination. Malay polyps were seen on barium-enema examination. Teleroentge nogram o fthe chest showed cardiomegaly, particularly right atrial enlargement (Fig. 7), but the EKG was normal (Fig. 8). An atrial septal defect and pulmonary stenosis were found as a result of hemodynamic examinations. Operation confirmed a septum secundum type o fatrial septal defect and valvular pulmonary stenosis. The diagnosis was juvenile polyposis of the colon with atrial septal defect and pulmonary valvular stenosis. Patient 3. A 4-year-old boy, the brother of Patients l and 2, corn plained of rectal bleeding and anal prolapse. Generalized pallor, clubbing of fingers, a systolic thrill, and a grade 3/6 systolic ejection m u r m u r in the pulmonary area were found on physical examination. Many" pedunculated polyps ranging in size from a few millimeters to 1-2 cm were seen on proctosigmoidoscopy. Cardiomegaly and right ventricular hypertrophy were evidenced by radiography and the EKG (Figs. 9 and 10). Hemodynamic findings indicated an atrial septal defect, p u l m o n a r y v a l v u l a r stenosis, and a n o m a l o u s puhnonary drainage (presumably between the puhnonary vein and superior vena cava). The diagnosis wasjuvenile polyposis of the colon, with atrial septal defect, pulmonary vaI~ ular stenosis, and abnormal venous drainage.
FIO. 2.
Rectosigmoidoscopic appearance of polyps, Patient l.
polyps ranging in size from a few millimeters to 1-2 cm (Fig. 2). Large cysts filled with abundant mucin, typical of juvenile polyps, were disclosed by histologic examination (Fig. 3). Polyps with many filling defects were observed on radiologic examination of the colon (Fig. 4). Teleroentgenogram of the chest was normal (Fig. 5). T h e EKG showed left axis deviation (Fig. 6). Hemodynamic examinations could not be completed. Consequently, a diagnosis of juvenile colonic polyposis, pulmonary stenosis, and suspected atrial septal defect was made.
Patient 4. A 30-year-old man was the father of the first three patients. He had complained of rectal bleeding and discharge of polyps since childhood. Generalized pallor, clubbing of fingers, and a grade 2/6 systolic ejection m u r m u r over the second left intercostal space were again found on physical examination. Likewise, many pedunculated polyps, ranging in size from a few millimeters to 1-2 cm, were seen on proctosigmoidoscopy. T h e histologic diagnosis was juvenile polyps. Barium-enema study also demonstrated many polyps. Teleroentgenogram was normal (Fig. 11). T h e EKG showed right axis deviation a n d incomplete right bundle-branch block (Fig. 12). T h e diagnosis was atrial septal defect and pulmonary stenosis. It was learned that the father of Patient 4 and the grandfather of Patients 1, 2 and 3, who was 50 years old, also had complaints of
FIG. 3. Histopathologic appearance of a polyp from Patient 1.
Volume 2i Number 7
P O L Y P O S I S A N D H E A R T DISEASE
503
rectal bleeding and discharge of polyps. However, despite all attempts, he could not be examined. The genetic aspect of the family was examined at the Department of Genetics, the Faculty of Medicine of the Hacettepe University, Ankara, and no chromosomal anomaly was found.
FIG. 4. Barium-enema study of Patient 1. Polyps are visible as numerous filling defects.
Fro. 6. EKG of Patient l, showing left axis deviation.
Discussion
Fm. 5.
Teleroentgenogram of Patient 1. Normal.
J u v e n i l e colonic polyposis has b e e n d e s c r i b e d as a s e p a r a t e entity by M o r s o n et al. 4's In a classification devised by Sachatello a n d G r i f f e n , ~ it is n o t e d that the g e n e t i c aspect o f j u v e n i l e colonic p o l y p o s i s is n o t clear, a n d that the disease manifests no p e c u l i a r signs o r s y m p t o m s o t h e r t h a n t h o s e a f f e c t i n g the gastrointestinal tract. T h e direct t r a n s m i s s i o n o f the disease f r o m the f a t h e r s to c h i l d r e n in two g e n e r a t i o n s o f the family we e x a m i n e d is associated with a clearly d o m i n a n t p e n e t r a t i n g gene, which a p p e a r s to be n o n - s e x linked in this family. It is n o t possible to e x p l a i n this p h e n o t y p e , o c c u r r i n g in t h e f a t h e r s a n d the two d a u g h t e r s as well as t h e son, in a n y o t h e r way. At the s a m e time, the g e n e c a u s i n g j u v e n i l e colonic polyposis in this family is r e l a t e d to the g e n e that causes c o n g e n -
504
Dis. Col. & Rect,
O N A R A N , E T AL.
FiG. 7. Teleroentgenogram of Patient 2, showing cardiomegaly, particularly right atrial enlargement.
ital h e a r t disease. Likewise, it seems that this second gene is p r o b a b l y d o m i n a n t and p e n e t r a t i n g but not sex-linked. T h e genetics o f congenital h e a r t disease are not fully u n d e r s t o o d . T h e genetic features o f the m o t h e r a n d the e n v i r o n m e n t u n d o u b t e d l y play imp o r t a n t roles, r but factors related to the age a n d n u m b e r o f p r e g n a n c i e s o f the m o t h e r can be ruled out. T h e a f f e c t e d children were the first children o f the y o u n g m o t h e r . F u r t h e r m o r e , congenital h e a r t
October 1978
FIG. 9. Teleroentgenogram of Patient 3, showing cardiomegaly and right ventricular hypertrophy.
Fro. 10. EKG of Patient 3, showing right axis deviation and right ventricular hypertrophy.
disease a n d juvenile colonic polyposis were f o u n d to be associated with each o t h e r in all cases, elucidating the genetics o f b o t h diseases. O n the o t h e r h a n d , the two diseases were f o u n d to affect the patients equally,
V o l u m e 21 Number 7
POLYPOSIS AND HEART DISEASE
505
thus indicating that the responsible genes are very closely r e l a t e d to e a c h o t h e r o r at least f o u n d in t h e same chromosome. I n t h e l i g h t o f t h e s e f i n d i n g s , we b e l i e v e t h a t we m a y h a v e e n c o u n t e r e d a n e w s y n d r o m e . T h e association of congenital heart disease and adenomatous p o l y p o s i s in a f a m i l y has b e e n r e p o r t e d o n l y o n c e : two patients from a family, a son and the father were a f f e c t e d ? I n a d d i t i o n , a v e n t r i c u l a r s e p t a l d e f e c t was p r e s e n t in o n e o f s e v e n cases o f i n f a n t i l e j u v e n i l e coIonic p o l y p o s i s , ~ b u t no case in w h i c h j u v e n i l e c o l o n i c p o l y p o s i s was a s s o c i a t e d w i t h c o n g e n i t a l h e a r t d i s e a s e has b e e n r e p o r t e d p r e v i o u s l y , r
Summary
FIG. 1 1. Teleroentgenogram of Patient 4. Normal.
Four members of a family with juvenile colonic p o l y p o s i s in two g e n e r a t i o n s w e r e e x a m i n e d by t h e authors. The disease showed a very marked dominant m o d e o f i n h e r i t a n c e , n o t s e x - l i n k e d , in this f a m i l y . A t the same time, the same members of the family had congenital heart disease, including atrial septal defects a n d p u l m o n a r y stenosis. T h i s d i s e a s e also r e suited from a dominant, highly penetrating gene, not sex-linked. The occurrence of both these hereditary d i s e a s e s at t h e s a m e t i m e s u g g e s t s a close r e l a t i o n ship o r link b e t w e e n the r e s p o n s i b l e genes. T h i s c o m bination may represent the emergence of a new syndrome.
References
FIo. 12. EKG of Patient 4, showing right axis deviation and incomplete right bundle-branch block.
I. Aim T, Licznerski G: The intestinal polyposes. Clin Gastroenterol 2:577 (Sept), 1973 2. Bussey HJ: Progress report: Gastrointestinal polyposis. Gut 11: 970, 1970 3. Gathright JR Jr, Cofer TW Jr: Familial incidence of juvenile polyposis coll. Surg Gynecol Obstet 138: 185, 1974 4. McColl I, Bussey HJ, Veale AM, et al: Juvenile polyposis coli. Proc R Soc Med 57: 896, 1964 5. Sachatetlo CR, Griffen WOJr: Hereditary polypoid diseases of the gastrointestinal tract: A working classification. Am J Surg 129: 198, 1975 6. Sachatello, CR, Hahn IS, Carrington CB: Juvenile gastrointestinal polyposis in a female infant: Report of a case and review of the literature of a recently recognized syndrome. Surgery 75: 107, 1974 7. Taylor wJ: Genetics and Cardiovascular System. In HurstJW: The Heart; Arteries and Veins. Ed 3, New York, McGrawHill Book Company, 1974, p 606 8. Veale AM, McCotl t, Bussey HJ, et al: Juvenile potyposis coil J Med Genet 3: 5, 1966
