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We report three related and one unrelated child with an apparently novel neurodevelopmental disorder. The clinical course was very similar in all the four patients: congenital microcephaly with severe failure of post-natal brain growth, neonatal onset of intractable seizures associated with lack of developmental progression and death within the first 3 years of life. The appearance on cerebral neuroimaging was almost identical, with simplified gyration associated with a non-thickened cortex, severe hypoplasia of the corpus callosum, a small flattened brain stem, and specific cystic lesions in the white matter around the temporal and occipital horns. To our knowledge these patients represent a previously unreported, autosomal recessive syndrome. Homozygosity mapping in the consanguineous family has identified a candidate region on the chromosome 2p16.

Myotonic dystrophy is a relatively common type of muscular dystrophy, associated with a variety of systemic complications. Long term follow-up is difficult because of the slow progression. The objective of this study was to determine survival, age at death and causes of death in patients with the adult-onset type of myotonic dystrophy. A register of myotonic dystrophy patients was set up in Southern Limburg (the Netherlands), using data longitudinally collected over a 47-year period (1950-97). Survival for 180 patients (from the register) with adult-onset type myotonic dystrophy was established by the Kaplan-Meier method. The median survival was 60 years for males and 59 years for females. Survival of the patients was also estimated from the age of 15 years to the ages of 25, 45 and 65 years and compared with the expected survival of age- and sex-matched birth cohorts from the normal Dutch population. The observed survival to the ages of 25, 45 and 65 years was 99%, 88% and 18% compared with an expected survival of 99%, 95% and 78%, respectively. Thus, survival to the age of 65 in patients with adult-onset myotonic dystrophy is markedly reduced. A weak positive correlation between the CTG repeat length and younger age at death was found in the 13 patients studied (r = 0.50, P = 0.08). The cause of death could be determined in 70 of the 83 deceased patients. Pneumonia and cardiac arrhythmias were the most frequent primary causes of death, each occurring in approximately 30%, which was far more than expected for the general Dutch population. In addition, we assessed mobility in the years before death in a subgroup of 18 patients, as a reflection of the long-term physical handicap in myotonic dystrophy patients. Half of the patients studied were either partially or totally wheelchair-bound shortly before their death.