The identified variations in DSP involve highly conserved residues. Moreover, the variations are de novo mutations and they are localised in critical protein domains that appear to be mutation hot spots. We assume that these heterozygous variations are causal for the mixed Naxos-Carvajal syndrome phenotype in the screened patients.

(ECG) showed pre-excitation and echocardiography revealed concentric hypertrophic cardiomyopathy with a septal and posterior wall thickness of 7-5 mm (normal 3-5-4-2 mm). There was no left or right ventricular outflow tract gradient. Treatment with digoxin and propanolol was introduced and there was no recurrence of the tachycardia.At the age of 10 months the boy showed failure to thrive with a weight of 7 kg (<3rd centile), length of 70 5 cm (10th centile), and microcephaly with a head circumference of 41-5 cm (<3rd centile). Furthermore nystagmus, prominent muscular weakness, and psychomotor retardation were evident. Screening for metabolic disorders revealed a slight acidosis with a pH of 7 34, carbon dioxide tension of 5-87 kPa, and increased lactate of 6-9 mmol/l in plasma and of 4.3 mmol/l in cerebrospinal fluid. The lactate/pyruvate and P-hydroxybutyric acid/ acetoacetate ratio in plasma were raised to 45 (normal <20) and 5-4 (normal <1) respectively; plasma carnitine was normal.Microscopic examination of striated muscle obtained by biopsy of quadriceps muscle showed mainly small fibres with augmented and enlarged fuchsinophilic drops in several enlarged fibres. Electromicroscopic examination revealed sparse myofibrils and focal accumulation of enlarged mitochondria that were morphologically abnormal. Biochemical analysis of this muscle biopsy specimen was performed as previously described7 and showed a reduced activity of complex I (3-2 mU/mg protein; controls 8-9-27 mU/mg protein) and complex IV (28 mU/mg protein; controls 52-186 mU/mg protein) of the respiratory chain. Total and 223 on 12 May 2018 by guest. Protected by copyright.

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Blood pressure measurements and Doppler echocardiography at rest and during exercise were performed in 36 patients at an average 17 years after coarctation resection. Interest focused on the study of Doppler systolic and diastolic gradients and half-times during exercise. Blood pressure gradients and Doppler values were compared with the degree of narrowing at the site of the anastomosis measured by magnetic resonance imaging. A systolic half-time of >110 ms together with a diastolic gradient of >/=17 mmHg on exercise Doppler sonography predicted a residual isthmic narrowing of >30%. We propose the use of this noninvasive method for identifying patients with narrowing of >30% at the site of the anastomosis after coarctation resection. In these cases evaluation by an imaging technique is necessary to confirm the need for surgery.

Seventeen years after coarctation repair, 36 patients were studied by magnetic resonance imaging and exercise testing to measure residual anatomical stenosis and hormonal response to exercise, and to evaluate their effect on arm-leg gradients and on exercise hypertension. The systolic arm pressure, leg pressure and arm-leg gradient were measured at rest and during exercise. Active renin and catecholamines were measured in the plasma at rest and after peak exercise. On magnetic resonance imaging 18 patients had residual stenosis of less than 30% (group I) and 18 had residual stenosis of equal to or more than 30% (group II). At peak exercise, the arm pressure was 235 (133-296) mmHg in group I and 241 (157-286) mmHg in group II (ns), the leg pressure was 138 (111-173) mmHg in group I and 114 (75-154) mmHg in group II (/>=0-002). The adrenalin increase from rest to exercise was 32-7 ± 91 pg . ml" ' in the patients with exercise hypertension and 31 ± 4-7 pg. ml ~' in the patients who remained normotensive during exercise (/ > =002). In conclusion, residual anatomical stenosis leads to a pressure drop in the legs, which influences the arm-leg gradient. Arm hypertension is not related to anatomical narrowing but to interaction of enhanced sympathetic nerve activity and structural and functional abnormality of the precoarctation vessels. (Eur Heart J 1996; 17: 1572-1575)