Kaplan–Meier survival curves of adult-onset myotonic dystrophy patients ( n ϭ 180); of the 101 males, 47 had died and the other 54 were censored; of the 79 women, 36 had died and the other 43 were censored. 

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... Only data on mean age at death for all disease types combined have been reported in older studies (Bell, 1948; Thomasen, 1948; Klein, 1958; Grimm, 1975). Our study aimed to determine the long-term prognosis of patients with adult-onset type myotonic dystrophy. We conducted a follow-up study by combining data collected by two generations of neurologists with a special interest in myotonic dystrophy. The age and causes of death were retrieved from the patients’ records and a survival analysis performed. In order to get an impression of the physical handicap in the years preceding death, mobility was assessed in a subgroup of patients. The population of patients for this study was selected from the register of myotonic dystrophy families in Southern Limburg. This region is a geographically isolated part of the Netherlands, bordered by Germany and Belgium. Ascertainment of complete families and follow-up of patients is relatively straightforward because of limited population migration. Between 1950 and 1970, 85 myotonic dystrophy patients from 15 families living in this area were examined (de Jong, 1955). The collection of data was continued from 1970 by the next generation of neurologists, working in the three regional hospitals in Maastricht, Heerlen and Sittard. After 1987 the series of family records were collated by the Department of Clinical Genetics and a genetic register set up. Data on disease type, major complications, results of DNA examination and genealogical studies were documented. The register presently contains data on 328 myotonic dystrophy patients from 56 families. For this study patients with the adult-onset type were selected from the register. This type is characterized by an age at onset between 10 and 50 years, myotonia and progressive weakness, and absence of mental retardation (Harley et al ., 1992). Congenital and childhood-onset cases were excluded because they show a high neonatal and childhood mortality and their prognosis was recently determined (Reardon et al ., 1993). Patients with mild disease (age at onset Ͼ 50 years) were not included because their prognosis seems to be much better than that for adult-onset patients. In total, 180 patients with adult-type myotonic dystrophy were selected, of which 83 (47 males and 36 females) were deceased at the time of surveying (January 1997). The age at death was ascertained by information from family members, medical records or from the registry office. The median and mean ages at death were determined for the whole population ( n ϭ 83) and for males and females separately. We calculated the mean age at death in order to compare our data with those from previous studies. Survival of the patients was estimated by the Kaplan–Meier method with the attained age as the survival time. Patients still alive at the end of follow-up were censored (in order to include follow-up information of all patients, deceased or still alive). Survival of the patients was also compared with the expected survival based on generation-survival tables from the Dutch population 1860–1989 (Tas, 1991). We calculated survival rates of the cohorts at risk from the age of 15 to 25 years (cohort born before 1972), to the age of 45 years (cohort born before 1952) and to the age of 65 years (cohort born before 1932). It was assumed that all patients survived at least to the age of 15 years. The 95% confidence intervals around the observed survival rates were calculated by the exact method using the binomial distribution. Exact P -values were also calculated from this distribution. The primary cause of death was known in 70 patients. Data on cause of death were obtained either from medical records, in the case of death in hospital, or from the general practitioner, in the case of death at home. Causes of death were grouped into two main categories: disease-related causes and causes not related to myotonic dystrophy. Sudden death, arrhythmias, pneumonia and postoperative death are well- known systemic complications of myotonic dystrophy (Aldridge, 1985; Harper, 1989; Mathieu et al ., 1997). We also considered fractures following a spontaneous fall as a myotonic dystrophy associated complication, as they probably occurred as a result of the muscle weakness. Some patients died following a series of events, e.g. a fracture after a fall, complicated by a fatal pneumonia. In these cases the initial event was recorded as the primary cause of death and the final complication leading to death as the secondary. An autopsy was performed in 22 patients. All autopsy reports were carefully reviewed. The observed frequencies of the different causes of death were compared with expected frequencies for the general Dutch population. The expected proportion of patients dying from a certain cause was calculated using Dutch population tables of causes of death from 1970 and 1990 (to represent, respectively, patients with median year of death 1965 and patients with median year of death 1991) and was further standardized for age and sex. The analysis was confined to primary causes of death that could be classified unambiguously by ICD (International Classification of Diseases) number (ICD-8, World Health Organization, Geneva 1967/1969 for 1970 and ICD-9, World Health Organization, Geneva 1978 for 1990). P -values were calculated from the binomial distribution. The length of the CTG repeat was known for only 13 patients, as most patients died before 1992, before the myotonic dystrophy gene was identified. Genomic DNA was isolated from peripheral blood cells. The molecular analyses were performed according to methods previously described (Shelbourne et al ., 1993). In the samples where smears were detected, the middle of the smear was sized. The expansions are expressed in kilobases of additional DNA. In a subgroup of 18 patients, mobility within 2 years of death was assessed during their regular visit to the outpatient clinic of neurology, and scored on a four-point scale (Hoffer et al ., 1973). The ages at death for the 83 deceased patients with adult- type myotonic dystrophy are shown in Fig. 1. The majority of patients (63%) died between the ages of 50 and 65 years. Only 12% of patients died aged 65 years or older. Further characteristics regarding the age at death are summarized in Table 1. Although mean and median ages at death were lower in male patients than in female patients, the observed differences were not statistically significant. The median (50%) survival for male patients was 59 years and for female patients 60 years (Table 1). The Kaplan– Meier curves (Fig. 2) show that survival in both sexes declined rapidly between the ages of 50 and 70 years, from ~80% of the cohort to ~10%. In Table 2, the observed survival from the age of 15 years in the 180 patients is compared with the expected survival. Survival of the patients to the age of 45 years was slightly, but significantly, lower than expected. Survival of patients to the age of 65 years was markedly reduced, only 18% compared with an expected survival of 78%. The observed survival to the age of 65 years was lower in males (11%) than in females (29%), but this difference was not statistically significant (Fisher’s exact test P ϭ 0.10). The molecular data for the 13 patients studied are given in Fig. 3. The mean CTG repeat size was 1.8 kb (600 CTG repeats) (range 0.5–4.7 kb). A weak inverse correlation between the CTG repeat length and survival was found ( r ϭ 0.50, P ϭ ...