Letter to the Editor

Brachmann-de Lange Syndrome and CongenitalHeart Disease

To the Editor:

We read with interest the article on the association ofBrachmann-de Lange syndrome (BDLS) and congeni-tal heart disease by Mehta and Ambalavanan [1997] inthis Journal. They found congenital heart defects(CHD) in 7 of 10 children with BDLS, and underlinedthe importance of performing an early cardiac evalua-tion in children with BDLS. We report here on the in-cidence rate of CHD among Japanese BDLS indivi-duals.

A total of 50 individuals from 10 hospitals was re-ported to have BDLS. All patients were diagnosed onthe basis of clinical manifestations by pediatric geneti-cists. Cardiac evaluations were performed by pediatriccardiologists. CHD was diagnosed in 13 of 50 (26%)individuals (8 males and 5 females) (Table I). Two in-dividuals died of causes other than CHD, and 11 arestill alive. CHD included ventricular septal defect (4cases), 2 with spontaneous closure, atrial septal defect(4 cases), atrial septal defect with pulmonary stenosis(1 case), ventricular septal defect with pulmonary ste-nosis (1 case), a combination of atrial septal defect,ventricular septal defect, and pulmonary stenosis (1case), endocardial cushion defect with tricuspid regur-gitation (1 case), and tetralogy of Fallot with pulmo-nary stenosis (1 case).

These findings suggest that CHD in patients withBDLS may reflect primary abnormalities of the heart.The incidence rate of CHD in the Japanese populationis 7 per 1,000 live births, almost the same rate as inCaucasians (8–10 per 1,000 live births) [Ando et al.,1977]. Hence, the rate of 13 of 50 Japanese individualsseems to be significantly higher than the rate of thegeneral population for CHD, suggesting the possibilityof a higher association of CHD in Japanese individualswith BDLS. Our findings also support previous reportsindicating the high prevalence of CHD in BDLS indi-viduals [Rao and Sissman, 1971; Hawley et al., 1985;

Filippi, 1989; Jackson et al., 1993; Kousseff et al., 1994;Mehta and Ambalavanan, 1997].

In conclusion, every patient with BDLS should beevaluated for possible congenital heart defects.

ACKNOWLEDGMENTS

This work was supported in part by a grant-in-aidfrom the Ministry of Health and Welfare of Japan.

REFERENCES

Ando M, Takao A, Mori K. (1977): Genetic and environmental factors incongenital heart disease. In Japan Medical Research Foundation (ed):‘‘Gene-Environment Interaction In Common Diseases.’’ Tokyo: Univer-sity of Tokyo Press, pp 71–78.

Filippi G (1989): The de Lange syndrome: Report of 15 cases. Clin Genet35:343–363.

Hawley PP, Jackson LG, Kurnit DM (1985): Sixty-four children withBrachmann-de Lange syndrome. A survey. Am J Med Genet 20:453–459.

Jackson L, Kline AD, Barr MA, Koch S (1993): De Lange syndrome: Aclinical review of 310 individuals. Am J Med Genet 47:940–946.

Kousseff BG, Newkirk P, Root AW (1994): Brachmann-de Lange syndrome:1994 update. Arch Pediatr Adolesc Med 148:1206–1208.

Mehta AV, Ambalavanan SK (1997): Occurrence of congenital heart dis-ease in children with Brachmann-de Lange syndrome. Am J Med Genet71:434–435.

Rao PS, Sissman NJ (1971): Congenital heart disease in the de Langesyndrome. J Pediatr 79:674–677.

Masato Tsukahara*School of Allied Health SciencesYamaguchi UniversityUbe, Japan

Contract grant sponsor: Ministry of Health and Welfare, Ja-pan.

*Correspondence to: Masato Tsukahara, M.D., School of AlliedHealth Sciences, Yamaguchi University, Ube, Yamaguchi-Ken755, Japan.

Received 3 October 1997; Accepted 3 October 1997

TABLE I. Congenital Heart Defects in Individuals With BDLS*

Present cases

ASD 4VSD 4a

ASD + PS 1VSD + PS 1ASD + VSD + PS 1ECD + TR 1TOF + PS 1

*ASD, atrial septal defect; VSD, ventricular septal defect; PS, pulmonarystenosis; ECD, endocardial cushion defect; TR, tricuspid regurgitation;TOF, tetralogy of Fallot.aTwo with spontaneous closure.

American Journal of Medical Genetics 75:441–442 (1998)

© 1998 Wiley-Liss, Inc.

Nobuhiko OkamotoDepartment of Planning and ResearchOsaka Medical Center and Research Institute for

Maternal and Child HealthOsaka, Japan

Hirofumi OhashiDivision of Medical GeneticsSaitama Children’s Medical CenterSaitama, Japan

Katsuko KuwajimaIbaraki Handicapped

Children’s HospitalIbaraki, Japan

Ikuko KondoDepartment of HygieneEhime University School of MedicineMatsuyama, Japan

Hideo SugieDepartment of Pediatric NeurologyHamamatsu City Medical Center for

Developmental MedicineHamamatsu, Japan

Toshiro NagaiDepartment of PediatricsKoshigaya HospitalDokkyo University School of MedicineKoshigaya, Japan

Kenji NaritomiDepartment of PediatricsUniversity of Ryukyus School of MedicineOkinawa, Japan

Tomoko HasegawaDivision of Clinical GeneticsShizuoka Children’s HospitalShizuoka, Japan

Yoshimitsu FukushimaDepartment of HygieneShinsyu University School of MedicineMatsumoto, Japan

Mitsuo MasunoYoshikazu KurokiDivision of Medical GeneticsKanagawa Children’s Medical CenterKanagawa, Japan

442 Tsukahara et al.