Deletions in the spinal muscular atrophy gene region in a newborn with neuropathy and extreme generalized muscular weakness.

A newborn presented with respiratory insufficiency requiring artificial ventilation, inability to swallow, lack of spontaneous movements including the facial muscles, and areflexia. Nerve conduction velocities were not recordable. Molecular analysis showed a homozygous deletion in the spinal muscular atrophy (SMN) gene region on chromosome 5q. Pathological and neuropathological examination revealed a normal number of anterior horn cells, hypomyelinated axons in peripheral nerves and some atrophy of skeletal muscle fibres in combination with sarcoplasmic glycogen accumulation. This observation illustrates that severe congenital neuropathy can result from deletions in the SMN gene.

[Treatment of acute myocardial infarction in Switzerland: is emergency PTCA more costly than thrombolysis?]. / Behandlungskosten des akuten Myokardinfarkts in der Schweiz: Ist die Akut-PTCA teurer als die Thrombolyse?

Confirming earlier studies with a lower number of patients, the Gusto IIb Angioplasty Substudy has shown that in the treatment of acute myocardial infarction emergency PTCA is superior to thrombolysis in reducing the combined clinical endpoints of death, reinfarction and cerebrovascular infarction. The aim of this study was to assess whether, in the Swiss study population of Gusto IIb, emergency PTCA was associated with higher procedural costs than thrombolysis over a median follow-up of 16 months. Therefore, we compared the costs of the initial and the follow-up hospitalisations. There were no differences in clinical characteristics in the Swiss subpopulation compared to the total study population. In a total of 46 patients, PTCA was performed in 22 and thrombolysis with rtPA in 24. During follow-up, 4 patients died, one in the PTCA group and 3 in the thrombolysis group (p = ns). The median total costs of the initial hospitalisation were somewhat higher in the PTCA group than in the group with thrombolysis. During follow-up only 38% of the patients in the PTCA group had to be rehospitalised, compared to 50% in the thrombolysis group. Median total costs within 16 months, therefore, were similar in the two therapeutic groups, but mean total costs per patient were somewhat lower for the PTCA versus the thrombolysis group (p = ns). Based on this comparison of Swiss procedural costs, emergency PTCA should not, in hospitals with the necessary infrastructure, be withheld in the treatment of acute myocardial infarction on the grounds of initially higher procedural costs, especially as the invasive strategy is associated with a more favourable long-term outcome.

Effects of morphologic restenosis, defined by MRI after coarctation repair, on blood pressure and arm-leg and Doppler gradients.

Ten years after coarctation repair, 36 adolescents and young adults were studied in order to evaluate the relationship of anatomy at the resection site to blood pressure and arm-leg and Doppler gradients. The patients underwent magnetic resonance imaging (MRI), exercise testing, and continuous wave (CW) Doppler echocardiography. On MRI, residual narrowing at the resection site was measured as 1-(phi anastomosis/ phi descending aorta) and expressed as percent stenosis. Residual stenosis on MRI was negatively correlated with the leg pressure at rest (P = 0.0003) and during exercise (P = 0.002). Residual stenosis correlated positively with the arm-leg gradient at rest (P < 0.0001) and during exercise (P < 0.0001) and with the peak CW Doppler gradient across the anastomosis (P < 0.0001). However, residual stenosis was not related to the systolic blood pressure of the arm at rest or during exercise. The systolic arm pressures did not differ between patients with residual stenosis of less than 30% (group I), patients with residual stenosis of equal to or greater than 30% but less than 45% (group II), and patients with residual stenosis of equal to or greater than 45% (group III). In conclusion residual anatomic stenosis influences blood pressure in the legs, the arm-leg gradient, and the Doppler gradient across the anastomosis. Arm hypertension late after coarctation repair seems not to be related to residual stenosis, and the benefit of reintervention in these patients remains questionable.

[Molecular genetic diagnosis and deletion analysis in Type I-III spinal muscular atrophy]. / Molekulargenetische Diagnose und Deletionsanalyse bei spinaler Muskelatrophie Typ I-III.

Autosomal recessive spinal muscular atrophy (SMA) is, after cystic fibrosis, the second most common fatal monogenic disorder. The disease is characterized by degeneration of anterior horn cells leading to progressive paralysis with muscular atrophy. Depending on the clinical type (Werdnig-Hoffmann = type I, intermediate form = type II, Kugelberg-Welander = type III), SMA causes early death or increasing disability in childhood. The SMA-critical region on the long arm of chromosome 5q13.1 contains many duplicated genes and polymorphisms. Recently, two presumptive SMA genes (survival motoneuron gene = SMN, and neuronal apoptosis inhibitory protein = NAIP) have been identified. Deletions involving critical regions of these genes are very often associated with SMA, and the extent of the deletions seems to correlate in part with disease severity. We have evaluated the diagnostic and prognostic value of molecular analysis in a large number of SMA patients. 57 patients and 78 healthy relatives were molecularly screened for deletions in the SMA critical region. We demonstrated homozygous deletions removing the SMN genes in over 90% of patients, whereas nearly 45% of patients exhibited NAIP gene deletions. Large deletions involving both genes on each chromosome are generally found in patients with severe SMA (Werdnig-Hoffman cases), while mildly affected Kugelberg-Welander cases frequently show only deleted SMN genes. Molecular classification based on combined deletion sizes, however, seems not to be exact, especially for the group with chronic SMA (type II and III). Direct DNA testing of patients in whom SMA is suspected is a highly reliable, fast, and noninvasive method. The ability to detect homozygous gene deletions in a high percentage of typical SMA patients will much improve genetic counselling and prenatal diagnosis in affected families.

[Ross syndrome]. / Das Ross-Syndrom.

We report on a 25-year-old patient with hyporeflexia, progressive segmental hypohidrosis and dry, scaly skin mimicking tinea manuum on the affected palm. This case is the fourth with Ross syndrome and skin manifestations as a result of segmental hypohidrosis.