The aim of the study was to establish the prevalence of cardiovascular malformations in females with Turner's syndrome and analyse possible associations with the various karyotypes. One hundred and seventy nine of 393 females who had Turner's syndrome diagnosed in Denmark were examined. Complete chromosome analysis was available in all cases. Clinical examination, electrocardiography, and echocardiography including Doppler were performed.The distribution of the various karyotypes was 45,X, 58%; mosaic monosomy X, 35%/o; and structural abnormalities of the X chromosome, 7%. In 46 (26%) of the females a total of 69 cardiovascular malformations were found; aortic valve abnormality (18%) and aortic coarctation (10%) being the most common. There was a significant difference in the prevalence of cardiovascular malformations between 45,X and mosaic monosomy X (38% v 1 1%), primarily due to a significant difference in the prevalence of aortic valve abnormalities and aortic coarctation. Pulmonary valve abnormalities were seen only in females with mosaic monosomy X but the prevalence was low (3%). No patient with structural abnormalities of the X chromosome had cardiovascular malformations.

In recent years, several genes have been causally associated with epilepsy. However, making a genetic diagnosis in a patient can still be difficult, since extensive phenotypic and genetic heterogeneity has been observed in many monogenic epilepsies. This study aimed to analyze the genetic basis of a wide spectrum of epilepsies with age of onset spanning from the neonatal period to adulthood. A gene panel targeting 46 epilepsy genes was used on a cohort of 216 patients consecutively referred for panel testing. The patients had a range of different epilepsies from benign neonatal seizures to epileptic encephalopathies (EEs). Potentially causative variants were evaluated by literature and database searches, submitted to bioinformatic prediction algorithms, and validated by Sanger sequencing. If possible, parents were included for segregation analysis. We identified a presumed disease-causing variant in 49 (23%) of the 216 patients. The variants were found in 19 different genes including SCN1A, STXBP1, CDKL5, SCN2A, SCN8A, GABRA1, KCNA2, and STX1B. Patients with neonatal-onset epilepsies had the highest rate of positive findings (57%). The overall yield for patients with EEs was 32%, compared to 17% among patients with generalized epilepsies and 16% in patients with focal or multifocal epilepsies. By the use of a gene panel consisting of 46 epilepsy genes, we were able to find a disease-causing genetic variation in 23% of the analyzed patients. The highest yield was found among patients with neonatal-onset epilepsies and EEs.

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We have carried out a case-controlled study on relations between short stature (i.e. less than 156 cm tall) and problems with childbirth in Danish women. Data obtained from 182 pregnant, short women (short mothers) were compared with those obtained from a control group of 2116 pregnant women who were between 166 and 175 cm tall (control mothers). The prevalence rate for acute cesarean section was three-fold greater in short mothers than in controls, and the prevalence rate for elective cesarean section was twice as high in short mothers as in controls. Moreover, the prevalence rates of intra-uterine asphyxia, intra-uterine growth retardation and low Apgar scores were higher in babies of short mothers than in those of control mothers, despite the increased level of obstetric intervention in the former group. Since the findings show that short stature in pregnant women is an obstetrical risk factor, we recommend that it should be given attention in order to detect early signs of intra-uterine asphyxia and to apply the best form of active management of labor if necessary.

As part of an ongoing study of the influence of environmental factors on pregnancy, childbirth, and fetuses, comparisons have been made between incidences in 1969-1974 and in 1980-1982 of chromosome aberrations in liveborn children in the same area of Denmark. The incidence of chromosome aberrations in the first period was 2.6 per 1000, compared with 41. per 1000 during the latter period. However, the difference was mainly due to an increase in inversions, and this in turn was due to a difference in chromosome staining methods between the two periods. It is concluded that the Danish study and similar studies in the United States, Canada, and Scotland indicate that early detection of chromosome aberrations by chromosome examination at birth is indicated in order to be able to inform and counsel parents of children with chromosome aberrations. Chromosome examination at birth is also of importance in the diagnosis of structural inheritable chromosome aberrations and consequent family investigation and genetic counseling.

Two families were referred with different clinical diagnoses of dystonia. Twenty-four family members were examined clinically, and mutation analyses were performed. Most of the affected individuals had laryngeal myoclonus and more severe dystonia of the legs than usually reported in myoclonus-dystonia syndrome. Sequence analyses revealed a previously unreported deletion (974delC or R325X) in exon 7 in the epsilon-sarcoglycan gene in members of both families. The two families were found to be related.

This study confirms the large variability in DRD symptoms and emphasizes the usefulness of molecular analysis for diagnosis and treatment of DRD. The presence of TS is suggested to be coincidental, though the development of TS-like symptoms due to mutations in GCH1 cannot be excluded.

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