American Journal of Medical Genetics 37532-533 (1990)

Brief Clinical Report Tetralogy of Fallot in Three Sibs Rainer Pankau, Werner Siekmeyer, and Regina Stoffregen Departments of Pediatrics ( R.P.) and Pediatric Cardiology (W.S., R.S.), University Hospital We report on three sibs (2 boys, one girl) with tetralogy of Fallot from non-consanguineous parents. The first child died during corrective surgery in 1972 from irreversible right ventricular failure. Corrective surgery was successful in the 2nd son and the daughter. The occurrence of tetralogy of Fallot in 3 sibs suggests a recessive gene.

KEY WORDS: familial, autosomal recessive inheritance, non-consanguineous

of

Kiel, West Germany

Fallot with pulmonary valve hypoplasia (Miller-LevPaul syndrome [Miller et al., 196211, and a right aortic arch (Table I) was confirmed a t cardiac catheterization. At age 12l/2 years corrective surgery was attempted. The patient died intraoperatively from irreversible right ventricular failure.

Patient 2 Patient 2 was born as the third child following a normal pregnancy. Birth weight was 3.25 kg. Early infancy was normal. At age 16 months he was admitted to the hospital with cyanotic spells resulting in loss of consciousness for 2 to 5 minutes. He had a moderate generalized cyanosis and a loud systolic murmur with maximal loudness in the region of the left 3rd and 4th intercostal spaces. Cardiac catheterization confirmed the diagnosis of tetralogy of Fallot with a right aortic arch (Table I). At age 6 years 7 months corrective surgery was performed. Now, a t age 23 years he has severe pulmonary valve regurgitation and mild peripheral pulmonary stenosis (Table I). A pulmonary valve replacement is planned.

INTRODUCTION The incidence of congenital heart defects is approximately 411,000 live births [Ferencz et al., 19851. The most common cardiac anomaly causing cyanosis is tetralogy of Fallot, representing 4 to 7.5% of all forms of congenital heart defects [Mitchell et al., 1971; Campbell, 1972; Boughman et al., 19871. Various mechanisms of inheritance with varying risk of recurrence were suggested for tetralogy of Fallot. Patient 3 There is evidence for multifactorial determination [Boon et al., 19721, as well as reports suggesting MenThe daughter was born a t term as the fourth child, delian inheritance [Lynch et al., 1966; Friedberg, 1974; following a normal pregnancy. Birth weight was 3.55 kg, Jones and Waldman, 1985; Der Kaloustian et al., 19851. length 49 cm. She had peripheral cyanosis a t birth. At We present a family in whom 3 of 5 children were age one year reduced exercise tolerance and central cyadiagnosed with tetralogy of Fallot without other malfor- nosis were apparent. mations. At age 2 % years, she was admitted to the hospital with generalized cyanosis, dyspnea on exertion, and CLINICAL REPORTS clubbing. There was a 316 systolic murmur in the region Patient 1 of the left 3rd and 4th intercostal spaces. Cardiac catheThe son was born a t term after a normal pregnancy, as terization confirmed the diagnosis of tetralogy of Fallot the first child. Birth weight was 2.75 kg, length 53 cm. (Table I) and a Blalock-Taussig shunt was performed. At age 4 years one month, cardiac catheterization was The mother was 20 years old and the father 37 years old repeated because of shunt dysfunction with failure to a t the time of birth. They are nonconsanguineous. Apart from recurrent infections, his early infancy was thrive, cyanosis, and severe tachydyspnea (Table I). At age 5% years, surgical correction was performed. normal. At age one year, the presence of a cardiac anomaly was suspected. A loud systolic murmur was present Postoperative cardiac catheterization showed a residual on auscultation without cyanosis or dyspnea. Bilateral pulmonary stenosis and a small residual ventricular cryptorchidism was noted. The diagnosis of tetralogy of septa1 defect (Table I). The patient is now 19 years old and asymptomatic. Received for publication October 13, 1989; revision received March 15, 1990. Address reprint requests to Rainer Pankau, M.D., Dept. Pediatrics, Schwanenweg 20, D-2300 Kiel 1, West Germany.

0 1990 Wiley-Liss, Inc.

DISCUSSION A study by Boon et al. [1972], in which the families of 106 patients with a tetralogy of Fallot were evaluated, showed a recurrence risk of 1%.The tendency of familial

Tetralogy of Fallot in Three Sibs

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TABLE I. Pre- and Postoperative Cardiac Catheterization Results, Clinical Data, and Summary of Course of the 3 Patients Patient Preoperative results _ _ _(sex) ___ Tetralogy of Fallot with 1 (male) pulmonary valve hypoplasia, severe ectasis of the pulmonary artery, right aortic arch; a t age 7 years, mild dyspnea, no cyanosis; weight: 18.4 kg; height: 119 cm Tetralogy of Fallot with right 2 (male) aortic arch; age 6% years. generalized cyanosis, dyspnea at rest; weight 19.8 kg; height: 120 cm 3 (female)

Tetralogy of Fallot; at age 4 years, generalised cyanosis and severe tachydyspnea; weight: 16.8 kg; height: 113 cm

- _Summary _ _ of -~ course -

Postoperative results

.~

Severe pulmonary insuficiency, mild peripheral pulmonary stenosis (left)

Mild residual pulmonary stenosis, mild pulmonary insufficiency, and small residual ventricular septa1 defect

aggregation was notable. Friedberg [19741 described a family with tetralogy of Fallot, in which 4 patients, in 3 successive generations, had various grades of pulmonary obstruction, from a mild stenosis to pulmonary atresia. Jones and Waldman [ 19851reported a n autosoma1 dominant syndrome of characteristic facial appearance, preauricular pits, fifth finger clinodactyly, and tetralogy of Fallot. Six patients in 3 generations showed various malformations. Three patients in 2 generations had a tetralogy of Fallot. Lynch et al. [19661 presented 2 children with tetralogy of Fallot, one of whom (male)was psychomotorically retarded with a chromosomal mosaic (46 XYi45 X). The sister showed no symptoms of Ullrich-Turner syndrome and a chromosome analysis was not performed. It was discussed whether the mosaic result and the cardiac anomaly were promoted by a common occurrence after fertilization, or, in view of the sister, whether a recessive gene was responsible for the tetralogy of Fallot, which then promoted the mosaic result. Der Kaloustian et al. [19851 described a family in whom 2 sisters had tetralogy of Fallot with pulmonary valve atresia. The parents were first cousins. There was no history of other affected relatives. A recessively inherited type of tetralogy of Fallot was suggested. In the family presented here, 3 of 5 children had nonsynchromae Tetralogy. Consequently a chromosome analysis was not performed. Neither of the parents had cardiac disease. The occurrence of tetralogy of Fallot in 3 sibs suggests a recessive gene. Variable expression of tetralogy reported here (one patient with Miller-Lev-Paul syndrome) and also by Friedberg [19741 does not contradict monogenetic inheritance. The right aortic arch in 2 of our patients is not an unusual finding considering that 25% of all patients

At age 12 years, moderate generalized cyanosis on exertion; weight: 30.5 kg; height: 146 cm; death a t age 12% years during surgery as the result of irreversible right ventricular failure in 1972 At age 6 years 7 months, corrective operation; at age 23 years, asymptomatic; weight: 98.6 kg; height 182 cm; pulmonary valve replacement is planned At age 2% years, BlalockTaussig shunt; a t age 5% years, corrective operation; at age 19 years, asymptomatic; weight: 56 kg; height: 171 cm

with tetralogy of Fallot have this association [Rao et al., 1971; Rees and Somerville, 19691.

ACKNOWLEDGMENT This work is dedicated to Prof. Dr. M. Tolksdorf on her 65th birthday.

REFERENCES Boon AR, Farmer MB, Roberts DF (1972): A family study of Fallot’s tetralogy. J Med Genet 9:179-188. Boughman JA, Berg KA, Astemborski JA, Clark EB, McCarter RJ, Rubin JD, Ferencz C (1987): Familial risks of congenital heart defect assessed in a population-based epidemiologic study. Am J Med Genet 26:839-849. Campbell M (1972): Nutural history of cyanotic malformation and comparison of all common cardiac malformations. Br Heart J 34:3-8. Der Kaloustian VM, Rat1 H, Malouf J, Hatem J, Slim M, Tomeh A, Khouri J, Kutayli F (1985): Tetralogy of Fallot with pulmonary atresia in siblings. Am J Med Genet 21:119-122. Ferencz C, Rubin JD, McCarter R J , Brenner JI, Neil1 CA, Perry LW, Hepner SI, Downing JW (1985): Congenital heart disease: Prevalence a t live birth. Am J Epidemiol 121:31-36. Friedberg DZ (1974): Tetralogy of Fallot with right aortic arch in three successive generations. Am J Dis Child 1272377-878. Jones MC, Waldman J D (1985):An autosomal dominant syndrome of characteristic facial appearance, preauricular pits, fifth finger clinodactyly and tetralogy of Fallot. Am J Med Genet 22:135-141. Lynch HT, Tips RL, Krush AJ (1966): Tetralogy of Fallot in two siblings. Am J Dis Child 11:304-307. Miller RA, Lev M, Paul H (1962):Congenital absence of the pulmonary valve. The clinical syndrome of tetralogy of Fallot with pulmonary regurgitation. Circulation 26:266-278. Mitchell FC, Korones SB, Berendes HW (1971):Congenital heart diseases in 56, 109 pers. Circulation 43:323-332. Rao BNS, Anderson RC, Edwards J E (1971): Anatomic variation in tetralogy of Fallot. Am Heart J 81:361-371. Rees S, Somerville J (1969): Aortography in Fallot’s tetralogy and variance. Br Heart J 31:146-153.

Tetralogy of Fallot in three sibs.

We report on three sibs (2 boys, one girl) with tetralogy of Fallot from non-consanguineous parents. The first child died during corrective surgery in...
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