Monitoring Dominant Germ Cell Mutations Using Skeletal Dysplasias Registered in Malformation Registries: An International Feasibility Study

Using data from seven malformation monitoring systems around the world, the feasibility of monitoring fresh dominant mutations using skeletal dysplasias was explored. Based on a total of over 9.5 million births, 1500 infants with skeletal dysplasias were identified (16 per 100000). In spite of effor...

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Bibliographic Details
Published in:International journal of epidemiology 1993-02, Vol.22 (1), p.107-115
Main Authors: KÄLLÉN, BENGT, KNUDSEN, LISBETH B, MUTCHINICK, OSVALDO, MASTROIACOVO, PIERPAOLO, LANCASTER, PAUL, CASTILLA, EDUARDO, ROBERT, ELISABETH
Format: Article
Language:English
Subjects:
Adult
age
Biological and medical sciences
Bone Diseases, Developmental - genetics
dysplasia
Feasibility Studies
Female
General aspects. Genetic counseling
Germ Cells - pathology
Humans
Infant, Newborn
inheritance
International Cooperation
man
Maternal Age
Medical genetics
Medical sciences
Mutation
mutation rates
Registries
Risk Factors
skeleton
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Summary:Using data from seven malformation monitoring systems around the world, the feasibility of monitoring fresh dominant mutations using skeletal dysplasias was explored. Based on a total of over 9.5 million births, 1500 infants with skeletal dysplasias were identified (16 per 100000). In spite of efforts to get exact diagnoses, an average of 21% were unspecified. Comparisons of rates of specific diagnoses in different programmes suggested that classification differed. By analysing maternal age distribution, estimates were made of the proportion of fresh mutations in different subgroups: conditions regarded as dominant (achondroplasia, thanatophoric dysplasia, spondyloepiphyseal dysplasia) were estimated to consist of 58% fresh mutations-some of the remaining cases were inherited, others were probably misclassified. Among conditions regarded as recessive, only 5% were estimated to be truly dominant mutations. In the total group of skeletal dysplasias, 21% were estimated to be fresh dominant mutations and if osteogenesis imperfecta were excluded, the figure was 31%. By power analyses it was shown that equal monitoring power may be obtained by a programme covering about 45 000 births per year with intensive diagnosis of each individual case of skeletal dysplasia and a programme some three times greater where no specific diagnoses are obtained. An increasing trend in the occurrence of skeletal dysplasias was seen but probably explained by changing ascertainment. An impact of antenatal diagnosis resulting in a decrease in occurrence was also apparent in some programmes.
ISSN:0300-5771
1464-3685
DOI:10.1093/ije/22.1.107