[Inversion of the circadian melatonin rhythm in Smith-Magenis syndrome]. / Inversion du rythme circadien de la mélatonine dans le syndrome de Smith-Magenis.

Smith-Magenis syndrome (SMS) is a genetic disease ascribed to an interstitial deletion on chromosome 17 (del 17p11); the prevalence is 1/25,000 births. The diagnosis is made on high-resolution karyotype confirmed by FISH. Clinical features include mild dysmorphism, short stature, other malformations (heart, renal, neurologic diseases). Mental retardation is constant; there are major behavioral disturbances and severe sleep disorders. We studied sleep disorders and melatonin secretion in SMS children and we have shown inversion of the circadian rhythm of melatonin, abnormally secreted during the day. This is the first biological model of behavioral and sleep disorder in a genetic disease. Therapeutic approach using beta-blockers in the morning and melatonin in the evening, reset circadian rhythm of melatonin, improve behavior and restore sleep.

[Predictive factors for late complete atrio-ventricular block after surgical treatment for congenital cardiopathy]. / Facteurs prédictifs de bloc auriculo-ventriculaire complet tardif après traitement chirurgical des cardiopathies congénitales.

The late occurrence of complete atrio-ventricular block (CAVB) after cardiac surgery is rare but potentially responsible for cases of late sudden death. We searched for factors allowing prediction of this complication, retrospectively reviewing the case notes of 11 patients in hospital with complete AVB, 2 months to 10 years after correction of a cardiac malformation. All had a normal pre-operative ECG. The diagnosis had been made based on symptoms in 8 patients: syncope or collapse (4 cases) symptoms on effort (3 cases) or fatigue (1 case). In the others the diagnosis had been made on ECG. The block was infra-His in 5 patients who had electrophysiology. ECG analysis showed that all the patients had CAVB immediately post-operatively lasting 3-14 days. After restoration of conduction the ECGs showed the following anomalies compared to the pre-operative ECGs: long PR (1 case), long PR + right bundle branch block (2 cases), long PR + left axis deviation (1 case), RBBB + left deviation or rotation of the QRS axis (3 cases), long PR + RBBB + left axis deviation (4 cases). All of these patients had been fitted with a cardiac stimulator. In conclusion, the children who had CAVB immediately post-operatively lasting more than 48 hours and who then had an ECG showing different QRS compared to the pre-operative QRS and/or long PR had a risk of late complete AVB. These patients should have electrophysiology and a stimulator must be implanted in those who have an infra-His block.

Impaired cardiac adrenergic innervation assessed by MIBG imaging as a predictor of treatment response in childhood dilated cardiomyopathy.

OBJECTIVE: To evaluate the prognostic value of metaiodobenzylguanidine (MIBG) imaging in childhood cardiomyopathy. DESIGN: Prospective cohort study. SETTING: Tertiary referral centre. PATIENTS: 40 children (21 boys, 19 girls; mean (SD) age, 7.0 (5.6) years) with heart failure resulting from idiopathic dilated cardiomyopathy (n = 23) or various other disorders (n = 17). METHODS: At the initial examination, cardiac (123)I-MIBG uptake and release, circulating noradrenaline (norepinephrine) concentration, x ray cardiothoracic ratio, and echocardiographic variables were recorded. Cardiac MIBG uptake was obtained by measuring the heart to mediastinum activity ratio on the planar image obtained four hours after MIBG injection. MIBG washout rate was evaluated using relative decrease in cardiac activity measured at 20 minutes and four hours. Patients were treated with angiotensin converting enzyme inhibitors, diuretics, and digitalis, and were followed up for 12 (10) months. Fifteen patients did not respond to medical treatment (12 heart transplants; three deaths), and 25 did respond (improved or stable). RESULTS: Cardiac MIBG uptake was positively correlated with x ray cardiothoracic index (r = 0.55, p = 0.0008) and echocardiographic left ventricular fractional shortening (r = 0.68, p < 0.0001). Among all the clinical and laboratory variables tested, multivariate discriminant analysis showed that the only independent predictor of an unfavourable outcome was a low MIBG uptake (p < 0.001). Survival curves had a mean threshold value of 1.54 for MIBG uptake. CONCLUSIONS: Impaired cardiac adrenergic innervation is strongly related to adverse outcome in children with dilated cardiomyopathy, independently of the aetiology. MIBG imaging may help to stratify risk in such patients.

[Neonatal cardiac failure secondary to hypocalcemia caused by maternal vitamin D deficiency]. / Insuffisance cardiaque néonatale secondaire à une hypocalcémie par carence maternelle en vitamine D.

BACKGROUND: Heart failure is a rare manifestation of neonatal hypocalcemia. This paper describes such a case resulting from maternal vitamin D deficiency. CASE REPORT: A full-term boy, born in December after a normal pregnancy, was admitted at the age of 6 weeks because of dyspnea that appeared during suckling. Examination showed heart failure. Electrocardiogram showed that the corrected QT-interval was lengthened (0.54 s, normal < 0.45 s). Echocardiogram showed dilated, hypokinetic myocardiopathy. His serum calcium concentration was low (1.40 mmol/l) and phosphate was high (2.8 mmol/l); his alkaline phosphatase was 513 Ul/l. His blood PTH concentration was high (120 pg/ml) and his 25 (OH) D was low (5 ng/ml). The patient was given calcium (1 g/m2/day) and 1.25 (OH)2 D (2 micrograms/day orally). His serum calcium returned to normal within 4 days, and his cardiac abnormality was resolved within 3 months. His mother's blood 25 (OH) D concentration was very low (3 ng/ml), 6 weeks after birth. CONCLUSION: Neonatal hypocalcemia appears to have been compounded in this case by a maternal vitamin D deficiency. Hence, all pregnant women at risk of deficiency should be given vitamin D.