An excess of twins in families with the Martin-Bell or fra(X) syndrome was noted previously in one family study [Fryns, 1986]. We tried to confirm this observation in a second large sample of families from a different population. We calculated the number of twin births among the total number of live births of known obligate carriers found in fra(X) families ascertained in New South Wales, Australia. We only included births of known sex and excluded triplets. There were 5 male pairs, 3 female pairs and 9 unlike sex pairs of twins born among 752 live births. Thus the twining rate was 1/44 per live birth. We compared this rate to that found in two different types of individuals: 1) the rate of 1/96 which was obtained from the 1985 vital statistics for New South Wales, and 2) the rate 1/75 obtained from a sample of live births of obligate carriers with hemophilia A. The increase in twinning among heterozygotes with the fra(X) was highly significant when compared to the census data (p less than 0.001). However, it was not significantly different from that in the hemophilia data (p less than 0.05) which were collected in the same way as in the fra(X) families.

Epidemiologic Methods↗

PubMedDate not supplied

Investigation of the segregation of the fragile X mutation in daughters of obligate carrier women.

Two reports have suggested that over 50% of the offspring of obligate carrier women receive the mutation for the fra(X) or the Martin-Bell syndrome [Webb et al, 1986; Fryns, 1984]. Such a segregation distortion is difficult to assess for the fra(X) syndrome because of incomplete penetrance, variable expression and probable ascertainment biases. We have attempted to evaluate this possible segregation distortion in daughters of obligate carriers in a large sample of sibships ascertained in a survey of New South Wales, Australia. We used two definitions of expression: 1) presence of fra(X) positive cells if daughters were tested cytogenetically, and 2) mental impairment if daughters were not tested cytogenetically. The segregation frequency was estimated in different types of sibships of obligate carriers based on the way they were ascertained. This was done in order to have an internal check on possible ascertainment biases. Among the 189 cytogenetically tested daughters, 81 were fra(X) positive. Among the 97 untested daughters, 24 were mentally impaired in some way. Therefore, the segregation frequency as defined by fra(X) expression and/or mental impairment was 37%. Thus, no evidence was detected for segregation distortion. These data were significantly different than those collected by Webb et al [1986] and scored by the same method as the present data set.

Female↗

PubMedDate not supplied

Clinical screening score for the fragile X (Martin-Bell) syndrome.

A clinical score based on the manifestations of the fragile(X) syndrome has been formulated and applied to all individuals included in a fragile(X) case finding program in New South Wales. The total score can vary from 0 to 10. Individuals are scored 0, 1, or 2 in each of 5 categories considered indicative of the fragile(X) phenotype: family history of intellectual handicap, face length, ear configuration, personality, and body habitus. In a study of 1,206 individuals where the clinical scores were prospective (i.e., they had been given before the cytogenetic results were known) the percentage of those with the fragile(X) increased from 0.6% of those with scores of 4 or less to 14.6% with scores 5-7 and to 67% of those with scores 8-10. We have found the score simple to use in the circumstances where screening takes place (sheltered workshops and schools) and have reduced the number of individuals tested cytogenetically by 45%.

Cross-Sectional Studies↗

PubMedDate not supplied

Mortality in the fragile X syndrome: preliminary data.

Mortality was studied among 348 males and 433 females who had or who carried the gene for the fragile X syndrome. The average age of death was about 12 years lower than in the general population for both men and women but this was likely a bias of ascertainment. The commonest causes of death were cardiovascular, cerebrovascular and malignant disease similar to those in the general population. No evidence for any specific disease susceptibility was found in this preliminary study.

Adolescent↗