The mortality of 48 de Lange patients born 1917-82 was found slightly raised compared with the expected number of deaths, and the survival rates appeared to be lowered. No sex differences were observed. The causes of death and the pathological findings were evaluated in 11 patients. Pneumonia was the most frequent cause of death (6 patients). Congenital malformations seemed to be contributory causes of death in 5 patients, the most frequent being congenital heart disease and gastro-intestinal malformations. A wide variety of malformations were found but no consistent macroscopic or microscopic abnormalities could be demonstrated. An incidence figure of 1:50 000 was found for the years 1967-82.

The concentration of human platelet lactogen (hPL), pregnancy specific beta-1 glycoprotein (SP-1) and pregnancy-associated plasma protein A (PAPP-A) were analysed in consecutive serum samples from a patient who gave birth to a child with Cornelia de Lange syndrome. HPL and SP-1 were present in normal concentrations from week 20 to week 35 of gestation whereas PAPP-A could not be detected in any of the samples examined. Immunohistochemical examination of two placentae from Cornelia de Lange syndrome revealed normal localization of hPL and SP-1 but the absence of PAPP-A from the syncytiotrophoblast. The significance of association between Cornelia de Lange syndrome and compromised synthesis of PAPP-A is discussed.

A prevalence investigation of Cornelia de Lange's syndrome in Denmark is presented. The patients were traced by screening all institutional mentally retarded patients, patients in schools and kindergartens for imbecile patients and finally by getting information on Cornelia de Lange patients known to pediatric departments. In this way 24 patients, 10 men and 14 women, were found. This amounts to a population prevalence of 0.5/100 000. Clinical data, histories of the patients and genealogical data are presented by means of tables. The eldest patient was 49 years old, but 75% of the patients were younger than 20 years. Two of the probands were sibs. Another 2 sibs were registered as mentally retarded without specific syndromes. One case of consanguinity among parents was found. The mode of ascertainment is discussed and it is concluded that the present investigation presents a minimum prevalence figure. Four patients are presented who for various reasons were not available during the prevalence investigation proper. A prevalence figure of 0.6/100 000 is found if these 4 patients are included in the calculations. One of the last mentioned patients represented a familial case. The patient in question was a girl with a younger half-brother, the mother in common, both children being very typical cases of Cornella de Lange's syndrome.

This paper summarizes previous chromosomal studies in patients with the Cornelia de Lange syndrome showing abnormal karyotypes. We report on 45 cases of the Cornelia de Lange syndrome clinically examined by one of us (B.B.) and chromosomally studied using several different methods. Two abnormal karyotypes were found: a girl with a 45,X karyotype and a boy with a (13q14q) translocation which was also found in his phenotypically normal mother and maternal grandmother. Because of recent reports of the duplication 3q syndrome and Cornelia de Lange-like phenotypes, prometaphase chromosomes were studied in 31 patients. All karyotypes were normal. As there was an excess of boys among the younger patients, special examination for the fragile site on X(q28) was carried out. This abnormality was not found. Even though no patients with the dup(3q) syndrome were found among the Cornelia de Lange patients, chromosome studies are recommended especially in connection with genetic counselling. A recurrence rate of 2-5% must still be considered for the Cornelia de Lange syndrome.