Severe neonatal asphyxia due to X-linked centronuclear myopathy.

Severe neonatal centronuclear myopathy is inherited as an X-linked condition characterized by primary asphyxia, extreme muscular hypotonia and absent spontaneous movements. We report seven cases from three families to point out the importance of diagnosis with regard to prognosis, outcome and genetic counselling. In hypotonic diseases, analysis of cerebrospinal fluid, electromyography, nerve conduction velocity creatine kinase and a skin biopsy for fibroblast cultures for metabolic investigations are usually carried out. Needle muscle biopsy is an additional valuable investigation to establish diagnosis. In all our patients we found an increased number of centrally located nuclei with perinuclear halos confirming the diagnosis of centronuclear myopathy. The diagnosis of this disorder will become of greater importance as soon as carrier detection and prenatal diagnosis by DNA-technology are routinely available.

Congenital nephrotic syndrome: clinico-pathological heterogeneity and prenatal diagnosis.

During the last five years, we have observed four families in which siblings were affected with the congenital nephrotic syndrome (CN). Clinically, all patients, with one exception, could barely be differentiated from classical examples of CN of the Finnish Type (CNF). Morphologically, however, each family showed a different type of CN, although the appearance in siblings was identical. This morphological heterogeneity, makes it likely that CN in a population outside Finland is the result of an unknown number of autosomal recessive mutations at different gene loci. In an attempt to diagnose CN prenatally by means of measurements of the concentration of alpha-fetoprotein in amniotic fluid, we found two false normal results, one in a patient with histologically confirmed CNF, another in a patient with CN, histologically non Finnish Type. Thus the results of prenatal diagnostic procedures for these disorders have to be reevaluated.