The diagnosis and frequency of X‐linked conditions in a cohort of moderately retarded males with affected brothers

Abstract

An epidemiological study was carried out on the group of moderately retarded brothers (IQ, 30–55) identified by Turner and Turner [1974]. Of the original 58 sets of brothers, 54 sets (now 17 to 32 years old) were traced; another four sets (missed in the earlier survey) were added. Forty‐five of the 58 pairs were diagnosed as having nonspecific X‐linked mental retardation (MR) giving an overall frequency of 5.57 moderately retarded males/10,000 male births. In 12 of the 45 families, affected males had the fragile(X) and macroorchidism; six had macroorchidism alone, giving a frequency of 2.8 moderately retarded males with X‐linked MR and macroorchidism ± the fragile(X) per 10,000 males. Corresponding heterozygote frequencies are 7.34 and 3.65/10,000 females respectively. A new subgrouping of nonspecific X‐linked mental retardation is described in six families: X‐linked MR, macroorchidism without the fragile(X). Three other X‐linked conditions were identified: in one family, the Coffin‐Lowry syndrome, in another, Duchenne muscular dystrophy, and in two families X‐linked MR and muscle atrophy. Half (56%) of the obligatory carriers of fra(X)‐MR in this study were dull to mildly retarded. The mildly retarded heterozygotes had a significantly higher percentage of fra(X) expressing lymphocytes as compared to the intellectually normal heterozygotes. When the three types of nonspecific X‐linked MR for which population frequencies were calculated were considered together, half of the obligatory carriers (46%) were dull or mildly retarded, thus confirming that this condition is a significant cause of mild intellectual handicap in females.