Apert's syndrome (a type of acrocephalosyndactyly)–observations on a British series of thirty‐nine cases*

Abstract

Summary: Acrocephalosyndactyly may be divided into two main clinical categories: (i) Apert's syndrome, and (ii) atypical acrocephalosyndactyly. Apert's syndrome can be attributed to a single gene in heterozygous form. On this hypothesis sporadic cases are due to new mutation in the germ cells of one or other parent. Although it is convenient at present to speak of the syndrome as homogeneous, there are indications, namely, the difference in parental age distribution between sporadic cases with severe developmental deformity of the viscera and sporadic cases without known visceral deformity, that this might not be so. The incidence at birth of Apert's syndrome is estimated as approximately 1 in 160,000 and that in the general population as 1 in 2,000,000. The difference between these estimates is in part due to lack of ascertainment in the living population and in part due to the high mortality of these patients, particularly in early infancy. The rate of mutation at the Apert locus is estimated to be 3 times 10‐6 per gene per generation. There is a marked parental age effect among sporadic cases of Apert's syndrome; this is probably due solely to an increase in father's age. Apert's syndrome and atypical acrocephalosyndactyly are probably etiologically unrelated. I am greatly indebted to Prof. Penrose for his interest and guidance throughout this study and especially for his advice on the statistical treatment of the parental age data. Thanks are due to Dr C. A. B. Smith for his guidance on various statistical matters and to Dr D. G. Harnden, Medical Research Council Unit, Harwell, for a report on the chromosomes of case 18. I would like to express my gratitude to the many medical practitioners, specialists and general practitioners, who have helped in the ascertainment and investigation of the patients in this series.